<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01723774</url>
  </required_header>
  <id_info>
    <org_study_id>201301106</org_study_id>
    <nct_id>NCT01723774</nct_id>
  </id_info>
  <brief_title>PD 0332991 and Anastrozole for Stage 2 or 3 Estrogen Receptor Positive and HER2 Negative Breast Cancer</brief_title>
  <official_title>A Phase II Trial of Neoadjuvant PD 0332991, a Cyclin-Dependent Kinase (Cdk) 4/6 Inhibitor, in Combination With Anastrozole in Women With Clinical Stage 2 or 3 Estrogen Receptor Positive and HER2 Negative Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A Phase II study to investigate the potential utility of PD 0332991 in the treatment of early&#xD;
      stage ER+ Human epidermal growth factor receptor 2 (HER2)- breast cancer, to investigate&#xD;
      whether the combination of PD 0332991 and anastrozole is able to: 1) improve the pathologic&#xD;
      complete response rate when compared to the historical control of single agent aromatase&#xD;
      inhibitors, 2) result in fewer patients with on therapy Ki67&gt;10% compared to historical&#xD;
      control.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 10, 2013</start_date>
  <completion_date type="Anticipated">April 30, 2027</completion_date>
  <primary_completion_date type="Actual">April 13, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (PIK3CA Wild Type Cohort Only)</measure>
    <time_frame>At cycle 1 day 15 (2 weeks)</time_frame>
    <description>Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (Endocrine Resistant Cohort Only)</measure>
    <time_frame>At cycle 1 day 15 (2 weeks)</time_frame>
    <description>Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 ( PIK3CA Mutant Type Cohort Only)</measure>
    <time_frame>At cycle 1 day 15 (2 weeks)</time_frame>
    <description>Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Complete Cell Cycle Arrest</measure>
    <time_frame>Cycle 1 day 1 and cycle 1 day 15 (2 weeks)</time_frame>
    <description>Compare rate of complete cell cycle arrest (defined as Ki67 ≤ 2.7%) arrest between C1D1 and C1D15</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Response Rate</measure>
    <time_frame>16 weeks</time_frame>
    <description>The clinical response rate is the number of patients whose disease meets the WHO criteria of complete or partial response prior to surgery divided by the total number of eligible patients who began combination neoadjuvant treatment.&#xD;
Complete Response (CR) is defined as the disappearance of all known disease based on a comparison between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there is no appearance of new lesions.&#xD;
Partial Response (PR) is defined as a 50% or greater decrease in the product of the bidimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there can be no appearance of new lesions or progression of any lesion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiologic Response Rate</measure>
    <time_frame>At the end of cycle 4 prior to surgery (estimated to be 16 weeks)</time_frame>
    <description>The radiological response rate is the number of patients whose disease meets with WHO criteria for complete or partial response at the evaluation prior to surgery divided by the total number of eligible patients who began combination neo-adjuvant therapy.&#xD;
Complete Response (CR) is defined as the disappearance of all known disease based on a comparison between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there is no appearance of new lesions.&#xD;
Partial Response (PR) is defined as a 50% or greater decrease in the product of the bidimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there can be no appearance of new lesions or progression of any lesion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events</measure>
    <time_frame>From start of treatment through 30 days after completion of an estimated 4 months of neoadjuvant therapy</time_frame>
    <description>The maximum grade for each type of adverse event will be recorded for each patient using the NCI-CTCAE v4.0 coding scheme, and frequency tables will be reviewed to determine patterns. Additionally, the relationship (possibly related, probably related, and definitely related) of the adverse event(s) to the study treatment will be taken into consideration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With a PEPI-0 Score</measure>
    <time_frame>At the time of surgery (estimated to be 5 months)</time_frame>
    <description>Preoperative endocrine prognostic index (PEPI) score is derived from four factors assigned a numerical score following neoadjuvant endocrine therapy, including Ki67 expression in the surgical specimen, pathologic tumor size (indicated as &quot;T&quot; below), lymph node status (indicated as &quot;N&quot; below), and estrogen receptor (ER) level (indicated as ER Allred below).&#xD;
PEPI-0 score indicates T1 or T2, N0, Ki67 &lt; 2.7%, ER Allred &gt; 2.&#xD;
It predicts a low risk of recurrence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Ki67 Level of Tumor Specimens</measure>
    <time_frame>Pre-treatment and cycle 1 day 15</time_frame>
    <description>To assess Ki67 level on serially collected tumor specimens</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Ki67 Level of Tumor Specimens</measure>
    <time_frame>Cycle 1 day 15 and at time of surgery (approximately 2-4 weeks post completion of cycle 4 - each cycle is 28 days)</time_frame>
    <description>To assess Ki67 level on serially collected tumor specimens</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Pathologic Complete Response (pCR)</measure>
    <time_frame>At the time of surgery (estimated to be 5 months)</time_frame>
    <description>-A pathologic complete response is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event</measure>
    <time_frame>From start of adjuvant therapy through 30 days after completion of adjuvant therapy (estimated to be 2 years)</time_frame>
    <description>The maximum grade for each type of adverse event will be recorded for each patient using the NCI-CTCAE v4.0 coding scheme, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse-free Survival</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local Recurrence Rate</measure>
    <time_frame>5 years</time_frame>
    <description>Local recurrence is defined as histologic evidence of ductal carcinoma in situ or invasive breast cancer in the ipsilateral breast or chest wall.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Regional Recurrence Rate</measure>
    <time_frame>5 years</time_frame>
    <description>Regional recurrence is defined as the cytologic or histologic evidence of disease in the ipsilateral internal mammary, ipsilateral supraclavicular, ipsilateral infraclavicular and/or ipsilateral axillary nodes or soft tissue of the ipsilateral axilla.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distant Recurrence Rate</measure>
    <time_frame>5 years</time_frame>
    <description>Distant recurrence is defined as the cytologic, histologic, and/or radiographic evidence of disease in the skin, subcutaneous tissue, lymph nodes (other than local or regional metastasis), lung, bone narrow, central nervous system or histologic and/or radiographic evidence of skeletal or liver metastasis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Second Primary Breast Cancer</measure>
    <time_frame>5 years</time_frame>
    <description>Second primary breast cancer is defined histologic evidence of ductal carcinoma in situ or invasive breast cancer in the contralateral breast or chest wall.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Second Primary Cancer (Non-breast)</measure>
    <time_frame>5 years</time_frame>
    <description>Second primary cancer (non-breast) is defined as any non-breast second primary cancer other than squamous or basal cell carcinoma of the skin, melanoma in situ, or carcinoma in situ of the cervix is to be reported and should be confirmed histologically whenever possible.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">84</enrollment>
  <condition>Breast Neoplasms</condition>
  <arm_group>
    <arm_group_label>Arm 1: PIK3CA Wild Type Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2: PIK3CA Mutant Type Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 3: Endocrine Resistant Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PD0332991</intervention_name>
    <arm_group_label>Arm 1: PIK3CA Wild Type Cohort</arm_group_label>
    <arm_group_label>Arm 2: PIK3CA Mutant Type Cohort</arm_group_label>
    <arm_group_label>Arm 3: Endocrine Resistant Cohort</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anastrozole</intervention_name>
    <arm_group_label>Arm 1: PIK3CA Wild Type Cohort</arm_group_label>
    <arm_group_label>Arm 2: PIK3CA Mutant Type Cohort</arm_group_label>
    <arm_group_label>Arm 3: Endocrine Resistant Cohort</arm_group_label>
    <other_name>Arimidex®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Goserelin</intervention_name>
    <arm_group_label>Arm 1: PIK3CA Wild Type Cohort</arm_group_label>
    <arm_group_label>Arm 2: PIK3CA Mutant Type Cohort</arm_group_label>
    <arm_group_label>Arm 3: Endocrine Resistant Cohort</arm_group_label>
    <other_name>Zoladex®</other_name>
    <other_name>Decapeptide I</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgery (standard of care)</intervention_name>
    <description>-Breast and axillary lymph node surgery</description>
    <arm_group_label>Arm 1: PIK3CA Wild Type Cohort</arm_group_label>
    <arm_group_label>Arm 2: PIK3CA Mutant Type Cohort</arm_group_label>
    <arm_group_label>Arm 3: Endocrine Resistant Cohort</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Tumor biopsy</intervention_name>
    <arm_group_label>Arm 1: PIK3CA Wild Type Cohort</arm_group_label>
    <arm_group_label>Arm 2: PIK3CA Mutant Type Cohort</arm_group_label>
    <arm_group_label>Arm 3: Endocrine Resistant Cohort</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Pre-registration PIK3CA Mutant Inclusion&#xD;
&#xD;
          -  Clinical T2-T4c, any N, M0 invasive ER+ (Allred Score of 6-8) and HER2 negative (0 or&#xD;
             1+ by IHC or FISH negative for amplification) breast cancer, by AJCC 7th edition&#xD;
             clinical staging, with the goal being surgery to completely excise the tumor in the&#xD;
             breast and the lymph node. Note: Patients with invasive ER+ (Allred Score of 6-8)&#xD;
             HER2- breast cancer or DCIS in the contralateral breast the patient are eligible&#xD;
&#xD;
          -  Female ≥18 years of age&#xD;
&#xD;
          -  ECOG performance status of 0, 1 or 2&#xD;
&#xD;
          -  Life expectancy &gt; 4 months&#xD;
&#xD;
          -  Premenopausal, patient must be willing to comply with pregnancy requirements&#xD;
&#xD;
          -  Adequate organ and marrow function&#xD;
&#xD;
               -  leukocytes ≥ 3,000/mcL&#xD;
&#xD;
               -  absolute neutrophil count ≥ 1,500/mcL&#xD;
&#xD;
               -  platelets ≥ 100,000/mcL&#xD;
&#xD;
               -  total bilirubin ≤ ULN&#xD;
&#xD;
               -  AST(SGOT)/ and ALT(SGPT) &lt; 2.5 X ULN&#xD;
&#xD;
               -  Creatinine ≤ ULN&#xD;
&#xD;
          -  Able to understand and willing to sign an IRB-approved written informed consent&#xD;
             document&#xD;
&#xD;
        Exclusion&#xD;
&#xD;
          -  Prior treatment of this cancer including: surgery, radiation, chemotherapy,&#xD;
             biotherapy, hormonal therapy, investigational agent prior to study entry&#xD;
&#xD;
          -  Receiving any investigational agents&#xD;
&#xD;
          -  Prior therapy with any Cdk4 inhibitor&#xD;
&#xD;
          -  Any of the following in the previous 6 months: myocardial infarction, severe/unstable&#xD;
             angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure,&#xD;
             cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to: ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris,&#xD;
             uncontrolled symptomatic cardiac arrhythmia, psychiatric illness/social situations&#xD;
             that would limit compliance with study requirements&#xD;
&#xD;
          -  Pregnant/nursing&#xD;
&#xD;
          -  Unwilling to employ adequate contraception&#xD;
&#xD;
          -  Known HIV-positive on combination antiretroviral therapy&#xD;
&#xD;
          -  Evidence of inflammatory cancer&#xD;
&#xD;
          -  Known metastatic disease&#xD;
&#xD;
          -  Current use of anticoagulation therapy&#xD;
&#xD;
          -  Previous excisional biopsy of the breast cancer or sentinel lymph node biopsy&#xD;
&#xD;
          -  Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g.,&#xD;
             gastrointestinal tract disease resulting in an inability to take oral medication or a&#xD;
             requirement for IV alimentation, prior surgical procedures affecting absorption)&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to PD 0332991 or other agents used in the study&#xD;
&#xD;
          -  Corrected QT interval &gt;470 msec&#xD;
&#xD;
        Registration PIK3CA Mutant Inclusion The criteria below must be met in addition to the&#xD;
        pre-registration criteria, except treatment with endocrine therapy for this cancer is&#xD;
        allowed prior to registration&#xD;
&#xD;
          -  PIK3CA mutant cohort: tumor PIK3CA mutation present&#xD;
&#xD;
          -  Premenopausal women, serum estradiol level in postmenopausal range ≤ 7 days prior to&#xD;
             registration&#xD;
&#xD;
        Exclusion Criteria below must be met in addition to the pre-registration criteria -Current&#xD;
        use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors (i.e.&#xD;
        grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole,&#xD;
        erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir,&#xD;
        lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine)&#xD;
        or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital,&#xD;
        St. John's wort)&#xD;
&#xD;
        PIK3CA Wild Type Inclusion&#xD;
&#xD;
          -  Clinical T2-T4c, any N, M0 invasive ER+ (Allred Score of 6-8) and HER2 negative (0 or&#xD;
             1+ by IHC or FISH negative for amplification) breast cancer, by AJCC 7th edition&#xD;
             clinical staging, with the goal being surgery to completely excise the tumor in the&#xD;
             breast and the lymph node. Note: Patients with invasive ER+ (Allred Score of 6-8)&#xD;
             HER2- breast cancer or DCIS in the contralateral breast the patient are eligible&#xD;
&#xD;
          -  For the PIK3CA wild type cohort: tumor PIK3CA mutation absent. Note that if a patient&#xD;
             did not have sufficient research tissue for PIK3CA sequencing at pre-registration or&#xD;
             if PIK3CA sequencing result is delayed, she could be registered and enrolled on the&#xD;
             PD991 trial without assigning to a particular cohort at the time of enrollment. PIK3CA&#xD;
             sequencing will be performed in the future on tumors collected at subsequent time&#xD;
             points to assign the treatment cohort or when the PIK3CA sequencing data is available&#xD;
&#xD;
          -  For the endocrine resistant cohort: Ki67 &gt; 10% by central testing at Washington&#xD;
             University AMP laboratory from a tumor biopsy performed after at least 2 weeks on&#xD;
             neoadjuvant endocrine therapy. Note that prior neoadjuvant endocrine therapy could&#xD;
             include any endocrine therapy (including aromatase inhibitor, tamoxifen, fulvestrant)&#xD;
             alone or in combination, or endocrine therapy in combination with any investigational&#xD;
             agent that is not a Cdk 4/6 inhibitor&#xD;
&#xD;
             *Patients who had a Day 17 Ki67 &gt; 10% from the NCI9170 trial are eligible for the&#xD;
             endocrine resistant cohort&#xD;
&#xD;
          -  Female &gt;18 years of age&#xD;
&#xD;
          -  ECOG performance status of 0, 1 or 2&#xD;
&#xD;
          -  Life expectancy &gt; 4 months&#xD;
&#xD;
          -  If premenopausal, patient must be willing to comply with pregnancy requirements&#xD;
&#xD;
          -  Adequate organ and marrow function:&#xD;
&#xD;
               -  leukocytes ≥ 3,000/mcL&#xD;
&#xD;
               -  absolute neutrophil count ≥ 1,500/mcL&#xD;
&#xD;
               -  platelets ≥ 100,000/mcL&#xD;
&#xD;
               -  total bilirubin ≤ ULN&#xD;
&#xD;
               -  AST(SGOT)/ and ALT(SGPT) &lt; 2.5 X ULN&#xD;
&#xD;
               -  Creatinine ≤ ULN&#xD;
&#xD;
          -  In premenopausal women, serum estradiol level in postmenopausal range ≤ 7 days prior&#xD;
             to registration.&#xD;
&#xD;
          -  Able to understand and willing to sign an IRB-approved written informed consent&#xD;
             document&#xD;
&#xD;
        Exclusion&#xD;
&#xD;
          -  Prior treatment of this cancer including: Surgery, Radiation therapy, Chemotherapy,&#xD;
             Biotherapy, Hormonal therapy, Investigational agent prior to study entry&#xD;
&#xD;
          -  Receiving any other investigational agents&#xD;
&#xD;
          -  Prior therapy with any Cdk4 inhibitor&#xD;
&#xD;
          -  Any of the following in the previous 6 months: myocardial infarction, severe/unstable&#xD;
             angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure,&#xD;
             cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to: ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris,&#xD;
             uncontrolled symptomatic cardiac arrhythmia, psychiatric illness/social situations&#xD;
             that would limit compliance with study requirements&#xD;
&#xD;
          -  Pregnant/nursing&#xD;
&#xD;
          -  Unwilling to employ adequate contraception&#xD;
&#xD;
          -  Known HIV-positive on combination antiretroviral therapy&#xD;
&#xD;
          -  Evidence of inflammatory cancer&#xD;
&#xD;
          -  Known metastatic disease&#xD;
&#xD;
          -  Current use of anticoagulation therapy&#xD;
&#xD;
          -  Previous excisional biopsy of the breast cancer or sentinel lymph node biopsy&#xD;
&#xD;
          -  Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g.,&#xD;
             gastrointestinal tract disease resulting in an inability to take oral medication or a&#xD;
             requirement for IV alimentation, prior surgical procedures affecting absorption)&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to PD 0332991 or other agents used in the study&#xD;
&#xD;
          -  Corrected QT interval &gt;470 msec&#xD;
&#xD;
          -  Current use or anticipated need for food or drugs that are known strong CYP3A4&#xD;
             inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole,&#xD;
             posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir,&#xD;
             ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone,&#xD;
             diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids,&#xD;
             progesterone, rifampin, phenobarbital, St. John's wort)&#xD;
&#xD;
        Endocrine Resistant Inclusion&#xD;
&#xD;
          -  Clinical T2-T4c at diagnosis or screening, any N, M0 invasive ER+ (Allred Score at&#xD;
             least 3 or &gt; 1% ER positivity) and HER2 negative (0 or 1+ by IHC or FISH negative or&#xD;
             equivocal) breast cancer, by AJCC 7th edition clinical staging, with the goal being&#xD;
             surgery to completely excise the tumor in the breast and the lymph node. Note:&#xD;
             Patients with invasive breast cancer that is ER pos, HER2 neg or equivocal or DCIS in&#xD;
             the contralateral breast are eligible; multi-focal diseases are not excluded. The&#xD;
             dominant lesion will be followed per protocol&#xD;
&#xD;
          -  Ki67 &gt; 10% by central testing at Washington University AMP laboratory from a tumor&#xD;
             biopsy performed after at least 2 weeks on neoadjuvant endocrine therapy. If Ki67 is &gt;&#xD;
             10% by local testing, the Ki67 slide and H&amp;E slide need to be reviewed by the study&#xD;
             pathologist to confirm eligibility (discuss with Study Chair). For patients external&#xD;
             to Washington University, please contact the Washington University coordinator by&#xD;
             email so that a screening ID# can be assigned prior to shipment of the slides&#xD;
&#xD;
          -  Female ≥ 18 years of age&#xD;
&#xD;
          -  ECOG performance status of 0, 1 or 2&#xD;
&#xD;
          -  Pre- or post-menopausal women are eligible. If premenopausal, patient must be willing&#xD;
             to comply with pregnancy requirements and agrees with GnRH agonist therapy for ovarian&#xD;
             suppression during the study&#xD;
&#xD;
          -  Adequate organ and marrow function:&#xD;
&#xD;
               -  Leukocytes ≥ 3,000/mcL&#xD;
&#xD;
               -  Absolute neutrophil count ≥ 1,500/mcL&#xD;
&#xD;
               -  Platelets ≥ 100,000/mcL&#xD;
&#xD;
               -  Total bilirubin ≤ ULN&#xD;
&#xD;
               -  AST(SGOT)/ and ALT(SGPT) &lt; 2.5 X ULN&#xD;
&#xD;
               -  Creatinine ≤ ULN&#xD;
&#xD;
          -  Able to understand and willing to sign an IRB-approved written informed consent&#xD;
             document&#xD;
&#xD;
        Exclusion&#xD;
&#xD;
          -  Prior treatment of this cancer including: Surgery, Radiation, Chemotherapy&#xD;
&#xD;
          -  Receiving any other investigational agents&#xD;
&#xD;
          -  Prior therapy with Cdk4 inhibitor&#xD;
&#xD;
          -  Any of the following in the previous 6 months: myocardial infarction, severe/unstable&#xD;
             angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure,&#xD;
             cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to: ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris,&#xD;
             uncontrolled symptomatic cardiac arrhythmia, psychiatric illness/social situations&#xD;
             that would limit compliance with study requirements&#xD;
&#xD;
          -  Pregnant/nursing&#xD;
&#xD;
          -  Unwilling to employ adequate contraception&#xD;
&#xD;
          -  Known HIV-positive on combination antiretroviral therapy&#xD;
&#xD;
          -  Known metastatic disease&#xD;
&#xD;
          -  Current use of anticoagulation therapy&#xD;
&#xD;
          -  Previous excisional biopsy of the breast cancer or sentinel lymph node biopsy&#xD;
&#xD;
          -  Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g.,&#xD;
             gastrointestinal tract disease resulting in an inability to take oral medication or a&#xD;
             requirement for IV alimentation, prior surgical procedures affecting absorption)&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to PD 0332991 or other agents used in the study&#xD;
&#xD;
          -  Corrected QT interval &gt;470 msec&#xD;
&#xD;
          -  Current use or anticipated need for food or drugs that are known strong CYP3A4&#xD;
             inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole,&#xD;
             posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir,&#xD;
             ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone,&#xD;
             diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids,&#xD;
             progesterone, rifampin, phenobarbital, St. John's wort)&#xD;
&#xD;
        Adjuvant Inclusion&#xD;
&#xD;
          -  Derived benefit from PD 0332991 in the neoadjuvant setting in this trial. This&#xD;
             includes the 26 patients who achieved complete cell cycle arrest only after the&#xD;
             addition of PD 0332991 (C1D1 Ki67 &gt;2.7% and C1D15 Ki67 ≤ 2.7%) from the main study&#xD;
             (PIK3CA WT, mutant, or unknown cohorts) as well as any patients who have a Ki67 ≤ 10%&#xD;
             on C1D15 biopsy in the endocrine resistant cohort&#xD;
&#xD;
          -  ECOG performance status of 0, 1 or 2&#xD;
&#xD;
          -  Premenopausal, patient must be willing to comply with pregnancy requirements laid out&#xD;
&#xD;
          -  Adequate organ and marrow function&#xD;
&#xD;
               -  leukocytes ≥ 3,000/mcL&#xD;
&#xD;
               -  absolute neutrophil count ≥ 1,500/mcL&#xD;
&#xD;
               -  platelets ≥ 100,000/mcL&#xD;
&#xD;
               -  total bilirubin ≤ ULN&#xD;
&#xD;
               -  AST(SGOT)/ and ALT(SGPT) ≤ 2.5 X ULN&#xD;
&#xD;
               -  Creatinine ≤ ULN&#xD;
&#xD;
          -  Underwent surgery of the breast and axilla for curative intent&#xD;
&#xD;
          -  At least 4 weeks post completion of adjuvant chemotherapy and radiation therapy if&#xD;
             indicated&#xD;
&#xD;
          -  Patients who already started on adjuvant hormonal therapy are eligible under the&#xD;
             following conditions:&#xD;
&#xD;
               -  For the 26 patients who enrolled in the initial cohorts and derived benefit from&#xD;
                  neoadjuvant PD 0332991 (C1D1 Ki67 &gt;2.7% and C1D15 Ki67 ≤ 2.7%), adjuvant PD&#xD;
                  0332991 should be initiated as soon as possible if adjuvant hormonal therapy has&#xD;
                  been initiated and the patient has completed radiation if indicated&#xD;
&#xD;
               -  For patients who enrolled in the endocrine resistant cohort and derived benefit&#xD;
                  from neoadjuvant PD 0332991 (C1D15 Ki67 ≤ 10%), adjuvant PD 0332991 should be&#xD;
                  initiated within 6 months or sooner after initation of adjuvant hormonal therapy&#xD;
&#xD;
          -  Able to understand and willing to sign an IRB-approved written informed consent&#xD;
             document&#xD;
&#xD;
        Exclusion&#xD;
&#xD;
          -  Any of the following in the previous 6 months: myocardial infarction, severe/unstable&#xD;
             angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure,&#xD;
             cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to: ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris,&#xD;
             uncontrolled symptomatic cardiac arrhythmia, ssychiatric illness/social situations&#xD;
             that would limit compliance with study requirements&#xD;
&#xD;
          -  Pregnant/nursing&#xD;
&#xD;
          -  Unwilling to employ adequate contraception&#xD;
&#xD;
          -  Known HIV-positive on combination antiretroviral therapy. -Known metastatic disease&#xD;
&#xD;
          -  Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g.,&#xD;
             gastrointestinal tract disease resulting in an inability to take oral medication or a&#xD;
             requirement for IV alimentation, prior surgical procedures affecting absorption)&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to PD 0332991 or other agents used in the study&#xD;
&#xD;
          -  Corrected QT interval &gt;470 msec&#xD;
&#xD;
          -  Current use or anticipated need for food or drugs that are known strong CYP3A4&#xD;
             inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole,&#xD;
             posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir,&#xD;
             ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone,&#xD;
             diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids,&#xD;
             progesterone, rifampin, phenobarbital, St. John's wort)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cynthia X Ma, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic - Scottsdale</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic - Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.siteman.wustl.edu</url>
    <description>Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine</description>
  </link>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>November 6, 2012</study_first_submitted>
  <study_first_submitted_qc>November 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 8, 2012</study_first_posted>
  <results_first_submitted>April 9, 2022</results_first_submitted>
  <results_first_submitted_qc>May 6, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">June 2, 2022</results_first_posted>
  <last_update_submitted>December 6, 2022</last_update_submitted>
  <last_update_submitted_qc>December 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anastrozole</mesh_term>
    <mesh_term>Goserelin</mesh_term>
    <mesh_term>Palbociclib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 29, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/74/NCT01723774/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Arm 1: PIK3CA Wild Type Cohort</title>
          <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
        </group>
        <group group_id="P2">
          <title>Arm 2: PIK3CA Mutant Type Cohort</title>
          <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
        </group>
        <group group_id="P3">
          <title>Arm 3: Endocrine Resistant Cohort</title>
          <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
        </group>
        <group group_id="P4">
          <title>Adjuvant Continuation</title>
          <description>Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Neoadjuvant</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="16"/>
                <participants group_id="P3" count="34"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="21"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="13"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Ki67 &gt; 10%</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disease progression</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>High estradiol</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Adjuvant</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Still on active treatment</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Arm 1: PIK3CA Wild Type Cohort</title>
          <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
        </group>
        <group group_id="B2">
          <title>Arm 2: PIK3CA Mutant Type Cohort</title>
          <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
        </group>
        <group group_id="B3">
          <title>Arm 3: Endocrine Resistant Cohort</title>
          <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="34"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="34"/>
            <count group_id="B4" value="84"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58" lower_limit="34" upper_limit="79"/>
                    <measurement group_id="B2" value="55" lower_limit="34" upper_limit="79"/>
                    <measurement group_id="B3" value="53" lower_limit="30" upper_limit="76"/>
                    <measurement group_id="B4" value="55.5" lower_limit="30" upper_limit="79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="34"/>
                    <measurement group_id="B4" value="84"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="28"/>
                    <measurement group_id="B4" value="77"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="24"/>
                    <measurement group_id="B4" value="70"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="34"/>
                    <measurement group_id="B4" value="84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (PIK3CA Wild Type Cohort Only)</title>
        <description>Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991</description>
        <time_frame>At cycle 1 day 15 (2 weeks)</time_frame>
        <population>Arm 2 and Arm 3 participants were not evaluable for this outcome measure as it is for Arm 1: PIK3CA Wild Type Cohort only. 5 participants in Arm 1 were not evaluable. 1 participant was not evaluable due to insufficient quality of specimen, 1 participant was not evaluable because she withdrew prior to starting treatment, 2 participants were not evaluable because there was no tumor present on biopsy, and 1 participant was not evaluable because she withdrew prior to cycle 1 day 15 biopsy.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: PIK3CA Wild Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: PIK3CA Mutant Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: Endocrine Resistant Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (PIK3CA Wild Type Cohort Only)</title>
          <description>Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991</description>
          <population>Arm 2 and Arm 3 participants were not evaluable for this outcome measure as it is for Arm 1: PIK3CA Wild Type Cohort only. 5 participants in Arm 1 were not evaluable. 1 participant was not evaluable due to insufficient quality of specimen, 1 participant was not evaluable because she withdrew prior to starting treatment, 2 participants were not evaluable because there was no tumor present on biopsy, and 1 participant was not evaluable because she withdrew prior to cycle 1 day 15 biopsy.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (Endocrine Resistant Cohort Only)</title>
        <description>Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991</description>
        <time_frame>At cycle 1 day 15 (2 weeks)</time_frame>
        <population>Arm 1 and Arm 2 participants were not evaluable for this outcome measure as it is for Arm 3: Endocrine Resistant Cohort only. 1 participant was not evaluable for this outcome measure as the participant did not have any tissue available at the cycle 1 day 15 biopsy.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: PIK3CA Wild Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: PIK3CA Mutant Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: Endocrine Resistant Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (Endocrine Resistant Cohort Only)</title>
          <description>Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991</description>
          <population>Arm 1 and Arm 2 participants were not evaluable for this outcome measure as it is for Arm 3: Endocrine Resistant Cohort only. 1 participant was not evaluable for this outcome measure as the participant did not have any tissue available at the cycle 1 day 15 biopsy.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 ( PIK3CA Mutant Type Cohort Only)</title>
        <description>Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991</description>
        <time_frame>At cycle 1 day 15 (2 weeks)</time_frame>
        <population>Arm 1 and Arm 3 participants were not evaluable for this outcome measure as it is for Arm 2: PIK3CA Mutant Type Cohort only.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: PIK3CA Wild Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: PIK3CA Mutant Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: Endocrine Resistant Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 ( PIK3CA Mutant Type Cohort Only)</title>
          <description>Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991</description>
          <population>Arm 1 and Arm 3 participants were not evaluable for this outcome measure as it is for Arm 2: PIK3CA Mutant Type Cohort only.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Complete Cell Cycle Arrest</title>
        <description>Compare rate of complete cell cycle arrest (defined as Ki67 ≤ 2.7%) arrest between C1D1 and C1D15</description>
        <time_frame>Cycle 1 day 1 and cycle 1 day 15 (2 weeks)</time_frame>
        <population>PIK3CA Wild Type Cohort - 5 participants not evaluable. 1 due to insufficient quality of specimen, 1 because she withdrew prior to starting treatment, 2 participants because there was no tumor present on biopsy, and 1 because she withdrew prior to cycle 1 day 15 biopsy. Endocrine Resistant Cohort-1 participant because no tissue available at the cycle 1 day 15 biopsy.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: PIK3CA Wild Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: PIK3CA Mutant Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: Endocrine Resistant Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Complete Cell Cycle Arrest</title>
          <description>Compare rate of complete cell cycle arrest (defined as Ki67 ≤ 2.7%) arrest between C1D1 and C1D15</description>
          <population>PIK3CA Wild Type Cohort - 5 participants not evaluable. 1 due to insufficient quality of specimen, 1 because she withdrew prior to starting treatment, 2 participants because there was no tumor present on biopsy, and 1 because she withdrew prior to cycle 1 day 15 biopsy. Endocrine Resistant Cohort-1 participant because no tissue available at the cycle 1 day 15 biopsy.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1 complete cell cycle arrest</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15 complete cell cycle arrest</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="16"/>
                    <measurement group_id="O3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Response Rate</title>
        <description>The clinical response rate is the number of patients whose disease meets the WHO criteria of complete or partial response prior to surgery divided by the total number of eligible patients who began combination neoadjuvant treatment.&#xD;
Complete Response (CR) is defined as the disappearance of all known disease based on a comparison between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there is no appearance of new lesions.&#xD;
Partial Response (PR) is defined as a 50% or greater decrease in the product of the bidimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there can be no appearance of new lesions or progression of any lesion.</description>
        <time_frame>16 weeks</time_frame>
        <population>7 participants in Arm 1 were not evaluable for this outcome measure. 3 participants in Arm 2 were not evaluable for this outcome measure. 12 participants in Arm 3 were not evaluable for this outcome measure. Reasons include patient withdrawal (n=4), progressive disease during cycle 1 (n=2), cycle 1 day 15 Ki67 &gt;10% (n=14) high estradiol (n=1), and adverse event (n=1).</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: PIK3CA Wild Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: PIK3CA Mutant Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: Endocrine Resistant Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Response Rate</title>
          <description>The clinical response rate is the number of patients whose disease meets the WHO criteria of complete or partial response prior to surgery divided by the total number of eligible patients who began combination neoadjuvant treatment.&#xD;
Complete Response (CR) is defined as the disappearance of all known disease based on a comparison between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there is no appearance of new lesions.&#xD;
Partial Response (PR) is defined as a 50% or greater decrease in the product of the bidimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there can be no appearance of new lesions or progression of any lesion.</description>
          <population>7 participants in Arm 1 were not evaluable for this outcome measure. 3 participants in Arm 2 were not evaluable for this outcome measure. 12 participants in Arm 3 were not evaluable for this outcome measure. Reasons include patient withdrawal (n=4), progressive disease during cycle 1 (n=2), cycle 1 day 15 Ki67 &gt;10% (n=14) high estradiol (n=1), and adverse event (n=1).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Radiologic Response Rate</title>
        <description>The radiological response rate is the number of patients whose disease meets with WHO criteria for complete or partial response at the evaluation prior to surgery divided by the total number of eligible patients who began combination neo-adjuvant therapy.&#xD;
Complete Response (CR) is defined as the disappearance of all known disease based on a comparison between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there is no appearance of new lesions.&#xD;
Partial Response (PR) is defined as a 50% or greater decrease in the product of the bidimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there can be no appearance of new lesions or progression of any lesion.</description>
        <time_frame>At the end of cycle 4 prior to surgery (estimated to be 16 weeks)</time_frame>
        <population>Arm 1 PIK3CA Wild Type Cohort: 23 participants not evaluable due to imaging not being performed. Arm 2 PIK3CA Mutant Type Cohort: 9 participants not evaluable due to imaging not being performed. Arm 3 Endocrine Resistant Cohort: 10 participants not evaluable due to imaging not being performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: PIK3CA Wild Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: PIK3CA Mutant Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: Endocrine Resistant Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
        </group_list>
        <measure>
          <title>Radiologic Response Rate</title>
          <description>The radiological response rate is the number of patients whose disease meets with WHO criteria for complete or partial response at the evaluation prior to surgery divided by the total number of eligible patients who began combination neo-adjuvant therapy.&#xD;
Complete Response (CR) is defined as the disappearance of all known disease based on a comparison between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there is no appearance of new lesions.&#xD;
Partial Response (PR) is defined as a 50% or greater decrease in the product of the bidimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there can be no appearance of new lesions or progression of any lesion.</description>
          <population>Arm 1 PIK3CA Wild Type Cohort: 23 participants not evaluable due to imaging not being performed. Arm 2 PIK3CA Mutant Type Cohort: 9 participants not evaluable due to imaging not being performed. Arm 3 Endocrine Resistant Cohort: 10 participants not evaluable due to imaging not being performed.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events</title>
        <description>The maximum grade for each type of adverse event will be recorded for each patient using the NCI-CTCAE v4.0 coding scheme, and frequency tables will be reviewed to determine patterns. Additionally, the relationship (possibly related, probably related, and definitely related) of the adverse event(s) to the study treatment will be taken into consideration.</description>
        <time_frame>From start of treatment through 30 days after completion of an estimated 4 months of neoadjuvant therapy</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: PIK3CA Wild Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: PIK3CA Mutant Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: Endocrine Resistant Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events</title>
          <description>The maximum grade for each type of adverse event will be recorded for each patient using the NCI-CTCAE v4.0 coding scheme, and frequency tables will be reviewed to determine patterns. Additionally, the relationship (possibly related, probably related, and definitely related) of the adverse event(s) to the study treatment will be taken into consideration.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 1/2 anemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 dry eye</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 constipation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 diarrhea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 dry mouth</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 dyspepsia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 flatulence</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 gastroesophageal reflux disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 gastrointestinal pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 mucositis oral</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 nausea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 oral pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 rectal pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 stomatitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 vomiting</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 chills</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 edema limbs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 fatigue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 fever</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 localized edema</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 shingles</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3/4 pneumonitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 sinusitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 urinary tract infection</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 seroma</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 alanine aminotransferase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3/4 alanine aminotransferase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 aspartate aminotransferase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3/4 aspartate aminotransferase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 lymphocyte count decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 neutrophil count decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3/4 neutrophil count decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 platelet count decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 weight loss</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 white blood cell decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3/4 white blood cell decreased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 anorexia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 hypercalcemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 hypocalcemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 hypokalemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 hyponatremia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 arthralgia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 back pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 bone pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 myalgia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 osteoporosis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 dizziness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 dysgeusia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 headache</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 memory impairment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 peripheral motor neuropathy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 peripheral sensory neuropathy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 confusion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 depression</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 insomnia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 pelvic pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 allergic rhinitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 cough</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 dyspnea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 epistaxis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 nasal congestion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 postnasal drip</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 sore throat</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 runny nose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 alopecia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 dry skin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 hyperhidrosis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 papulopustular rash</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 pruritus</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 rash maculo-papular</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3/4 rash maculo-papular</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 fever blister</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 itchy skin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 hot flashes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 1/2 hypertension</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With a PEPI-0 Score</title>
        <description>Preoperative endocrine prognostic index (PEPI) score is derived from four factors assigned a numerical score following neoadjuvant endocrine therapy, including Ki67 expression in the surgical specimen, pathologic tumor size (indicated as &quot;T&quot; below), lymph node status (indicated as &quot;N&quot; below), and estrogen receptor (ER) level (indicated as ER Allred below).&#xD;
PEPI-0 score indicates T1 or T2, N0, Ki67 &lt; 2.7%, ER Allred &gt; 2.&#xD;
It predicts a low risk of recurrence.</description>
        <time_frame>At the time of surgery (estimated to be 5 months)</time_frame>
        <population>Some participants were not evaluable for this outcome measure due to participant withdrawal and surgery not completed.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: PIK3CA Wild Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: PIK3CA Mutant Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: Endocrine Resistant Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a PEPI-0 Score</title>
          <description>Preoperative endocrine prognostic index (PEPI) score is derived from four factors assigned a numerical score following neoadjuvant endocrine therapy, including Ki67 expression in the surgical specimen, pathologic tumor size (indicated as &quot;T&quot; below), lymph node status (indicated as &quot;N&quot; below), and estrogen receptor (ER) level (indicated as ER Allred below).&#xD;
PEPI-0 score indicates T1 or T2, N0, Ki67 &lt; 2.7%, ER Allred &gt; 2.&#xD;
It predicts a low risk of recurrence.</description>
          <population>Some participants were not evaluable for this outcome measure due to participant withdrawal and surgery not completed.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Ki67 Level of Tumor Specimens</title>
        <description>To assess Ki67 level on serially collected tumor specimens</description>
        <time_frame>Pre-treatment and cycle 1 day 15</time_frame>
        <population>Only participants who had tissue available at the two time points were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: PIK3CA Wild Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: PIK3CA Mutant Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: Endocrine Resistant Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Ki67 Level of Tumor Specimens</title>
          <description>To assess Ki67 level on serially collected tumor specimens</description>
          <population>Only participants who had tissue available at the two time points were evaluable for this outcome measure.</population>
          <units>percentage of Ki67 in tumor sample</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="28"/>
                    <count group_id="O2" value="16"/>
                    <count group_id="O3" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.75" lower_limit="3.63" upper_limit="74.00"/>
                    <measurement group_id="O2" value="19.76" lower_limit="2.67" upper_limit="44.50"/>
                    <measurement group_id="O3" value="33.52" lower_limit="7.48" upper_limit="94.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                    <count group_id="O2" value="16"/>
                    <count group_id="O3" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.18" lower_limit="0.00" upper_limit="80.00"/>
                    <measurement group_id="O2" value="0.51" lower_limit="0.00" upper_limit="1.97"/>
                    <measurement group_id="O3" value="15.27" lower_limit="0.00" upper_limit="97.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Ki67 Level of Tumor Specimens</title>
        <description>To assess Ki67 level on serially collected tumor specimens</description>
        <time_frame>Cycle 1 day 15 and at time of surgery (approximately 2-4 weeks post completion of cycle 4 - each cycle is 28 days)</time_frame>
        <population>Only participants who had tissue available at the two time points were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: PIK3CA Wild Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: PIK3CA Mutant Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: Endocrine Resistant Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Ki67 Level of Tumor Specimens</title>
          <description>To assess Ki67 level on serially collected tumor specimens</description>
          <population>Only participants who had tissue available at the two time points were evaluable for this outcome measure.</population>
          <units>percentage of Ki67 in tumor sample</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.70" lower_limit="0.00" upper_limit="80.00"/>
                    <measurement group_id="O2" value="0.51" lower_limit="0.00" upper_limit="1.97"/>
                    <measurement group_id="O3" value="0.97" lower_limit="0.00" upper_limit="6.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At time of surgery</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.00" lower_limit="1.91" upper_limit="75.63"/>
                    <measurement group_id="O2" value="8.75" lower_limit="0.13" upper_limit="74.16"/>
                    <measurement group_id="O3" value="2.84" lower_limit="0.00" upper_limit="12.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Pathologic Complete Response (pCR)</title>
        <description>-A pathologic complete response is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes.</description>
        <time_frame>At the time of surgery (estimated to be 5 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm 1: PIK3CA Wild Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O2">
            <title>Arm 2: PIK3CA Mutant Type Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
          <group group_id="O3">
            <title>Arm 3: Endocrine Resistant Cohort</title>
            <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Pathologic Complete Response (pCR)</title>
          <description>-A pathologic complete response is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event</title>
        <description>The maximum grade for each type of adverse event will be recorded for each patient using the NCI-CTCAE v4.0 coding scheme, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.</description>
        <time_frame>From start of adjuvant therapy through 30 days after completion of adjuvant therapy (estimated to be 2 years)</time_frame>
        <posting_date>12/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <time_frame>5 years</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Relapse-free Survival</title>
        <time_frame>5 years</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Local Recurrence Rate</title>
        <description>Local recurrence is defined as histologic evidence of ductal carcinoma in situ or invasive breast cancer in the ipsilateral breast or chest wall.</description>
        <time_frame>5 years</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Regional Recurrence Rate</title>
        <description>Regional recurrence is defined as the cytologic or histologic evidence of disease in the ipsilateral internal mammary, ipsilateral supraclavicular, ipsilateral infraclavicular and/or ipsilateral axillary nodes or soft tissue of the ipsilateral axilla.</description>
        <time_frame>5 years</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Distant Recurrence Rate</title>
        <description>Distant recurrence is defined as the cytologic, histologic, and/or radiographic evidence of disease in the skin, subcutaneous tissue, lymph nodes (other than local or regional metastasis), lung, bone narrow, central nervous system or histologic and/or radiographic evidence of skeletal or liver metastasis.</description>
        <time_frame>5 years</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of Second Primary Breast Cancer</title>
        <description>Second primary breast cancer is defined histologic evidence of ductal carcinoma in situ or invasive breast cancer in the contralateral breast or chest wall.</description>
        <time_frame>5 years</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of Second Primary Cancer (Non-breast)</title>
        <description>Second primary cancer (non-breast) is defined as any non-breast second primary cancer other than squamous or basal cell carcinoma of the skin, melanoma in situ, or carcinoma in situ of the cervix is to be reported and should be confirmed histologically whenever possible.</description>
        <time_frame>5 years</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from start of treatment until 30 days following the last day of study treatment. One participant is still receiving active treatment. Average treatment length of 175.3 days (full range 5-1615 days)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Arm 1: PIK3CA Wild Type Cohort</title>
          <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
        </group>
        <group group_id="E2">
          <title>Arm 2: PIK3CA Mutant Type Cohort</title>
          <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
        </group>
        <group group_id="E3">
          <title>Arm 3: Endocrine Resistant Cohort</title>
          <description>Tumor biopsy for testing/research at baseline and Cycle 1 Day 15&#xD;
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)&#xD;
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.&#xD;
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
        </group>
        <group group_id="E4">
          <title>Adjuvant Continuation</title>
          <description>Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Hiatal hernia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="34" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Vision change</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Watering eyes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Bleeding gums</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Cracked tooth</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Gastrointestinal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hemorrhoidal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Loose tooth</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Rectal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Stomach cramping</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Body aches</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Cold symptoms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fat necrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nose pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Shingles</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Axilla infection from surgery</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Labia majora cyst</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Oral yeast infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Thrush</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hand wound</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Seroma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Cardiac troponin I increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="26" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Osteoporosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Middle ear inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Emotional</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Breast pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Genital lump</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pelvic pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Premature menopause</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Vaginal discharge</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Vaginal dryness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Vasomotor symptoms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dry throat</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Postnasal drip</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Runny nose</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Sinus disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Armpit pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Body odor</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Bullous dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fever blister</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Heat rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Itchy skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Macular lesion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nail changes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodyesthesia syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Papulopustular rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Psoriasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Lymphedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Superficial throbophlebitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Cynthia X. Ma, M.D., Ph.D.</name_or_title>
      <organization>Washington University School of Medicine</organization>
      <phone>314-362-9383</phone>
      <email>cynthiaxma@wustl.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01723774
org study id: 201301106
nct id: NCT01723774
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
A Phase II study to investigate the potential utility of PD 0332991 in the treatment of early
      stage ER+ Human epidermal growth factor receptor 2 (HER2)- breast cancer, to investigate
      whether the combination of PD 0332991 and anastrozole is able to: 1) improve the pathologic
      complete response rate when compared to the historical control of single agent aromatase
      inhibitors, 2) result in fewer patients with on therapy Ki67>10% compared to historical
      control.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (PIK3CA Wild Type Cohort Only)
time frame: At cycle 1 day 15 (2 weeks)
description: Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991
measure: Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (Endocrine Resistant Cohort Only)
time frame: At cycle 1 day 15 (2 weeks)
description: Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991
measure: Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 ( PIK3CA Mutant Type Cohort Only)
time frame: At cycle 1 day 15 (2 weeks)
description: Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991
measure: Number of Participants With Complete Cell Cycle Arrest
time frame: Cycle 1 day 1 and cycle 1 day 15 (2 weeks)
description: Compare rate of complete cell cycle arrest (defined as Ki67 ≤ 2.7%) arrest between C1D1 and C1D15
measure: Clinical Response Rate
time frame: 16 weeks
description: The clinical response rate is the number of patients whose disease meets the WHO criteria of complete or partial response prior to surgery divided by the total number of eligible patients who began combination neoadjuvant treatment.
Complete Response (CR) is defined as the disappearance of all known disease based on a comparison between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there is no appearance of new lesions.
Partial Response (PR) is defined as a 50% or greater decrease in the product of the bidimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there can be no appearance of new lesions or progression of any lesion.
measure: Radiologic Response Rate
time frame: At the end of cycle 4 prior to surgery (estimated to be 16 weeks)
description: The radiological response rate is the number of patients whose disease meets with WHO criteria for complete or partial response at the evaluation prior to surgery divided by the total number of eligible patients who began combination neo-adjuvant therapy.
Complete Response (CR) is defined as the disappearance of all known disease based on a comparison between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there is no appearance of new lesions.
Partial Response (PR) is defined as a 50% or greater decrease in the product of the bidimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there can be no appearance of new lesions or progression of any lesion.
measure: Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events
time frame: From start of treatment through 30 days after completion of an estimated 4 months of neoadjuvant therapy
description: The maximum grade for each type of adverse event will be recorded for each patient using the NCI-CTCAE v4.0 coding scheme, and frequency tables will be reviewed to determine patterns. Additionally, the relationship (possibly related, probably related, and definitely related) of the adverse event(s) to the study treatment will be taken into consideration.
measure: Number of Participants With a PEPI-0 Score
time frame: At the time of surgery (estimated to be 5 months)
description: Preoperative endocrine prognostic index (PEPI) score is derived from four factors assigned a numerical score following neoadjuvant endocrine therapy, including Ki67 expression in the surgical specimen, pathologic tumor size (indicated as "T" below), lymph node status (indicated as "N" below), and estrogen receptor (ER) level (indicated as ER Allred below).
PEPI-0 score indicates T1 or T2, N0, Ki67 < 2.7%, ER Allred > 2.
It predicts a low risk of recurrence.
measure: Change in Ki67 Level of Tumor Specimens
time frame: Pre-treatment and cycle 1 day 15
description: To assess Ki67 level on serially collected tumor specimens
measure: Change in Ki67 Level of Tumor Specimens
time frame: Cycle 1 day 15 and at time of surgery (approximately 2-4 weeks post completion of cycle 4 - each cycle is 28 days)
description: To assess Ki67 level on serially collected tumor specimens
measure: Number of Participants With Pathologic Complete Response (pCR)
time frame: At the time of surgery (estimated to be 5 months)
description: -A pathologic complete response is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes.
measure: Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event
time frame: From start of adjuvant therapy through 30 days after completion of adjuvant therapy (estimated to be 2 years)
description: The maximum grade for each type of adverse event will be recorded for each patient using the NCI-CTCAE v4.0 coding scheme, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
measure: Overall Survival
time frame: 5 years
measure: Relapse-free Survival
time frame: 5 years
measure: Local Recurrence Rate
time frame: 5 years
description: Local recurrence is defined as histologic evidence of ductal carcinoma in situ or invasive breast cancer in the ipsilateral breast or chest wall.
measure: Regional Recurrence Rate
time frame: 5 years
description: Regional recurrence is defined as the cytologic or histologic evidence of disease in the ipsilateral internal mammary, ipsilateral supraclavicular, ipsilateral infraclavicular and/or ipsilateral axillary nodes or soft tissue of the ipsilateral axilla.
measure: Distant Recurrence Rate
time frame: 5 years
description: Distant recurrence is defined as the cytologic, histologic, and/or radiographic evidence of disease in the skin, subcutaneous tissue, lymph nodes (other than local or regional metastasis), lung, bone narrow, central nervous system or histologic and/or radiographic evidence of skeletal or liver metastasis.
measure: Rate of Second Primary Breast Cancer
time frame: 5 years
description: Second primary breast cancer is defined histologic evidence of ductal carcinoma in situ or invasive breast cancer in the contralateral breast or chest wall.
measure: Rate of Second Primary Cancer (Non-breast)
time frame: 5 years
description: Second primary cancer (non-breast) is defined as any non-breast second primary cancer other than squamous or basal cell carcinoma of the skin, melanoma in situ, or carcinoma in situ of the cervix is to be reported and should be confirmed histologically whenever possible.
arm group label: Arm 1: PIK3CA Wild Type Cohort
arm group type: Experimental
description: Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
arm group label: Arm 2: PIK3CA Mutant Type Cohort
arm group type: Experimental
description: Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
arm group label: Arm 3: Endocrine Resistant Cohort
arm group type: Experimental
description: Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
intervention type: Drug
intervention name: PD0332991
arm group label: Arm 1: PIK3CA Wild Type Cohort
arm group label: Arm 2: PIK3CA Mutant Type Cohort
arm group label: Arm 3: Endocrine Resistant Cohort
intervention type: Drug
intervention name: Anastrozole
arm group label: Arm 1: PIK3CA Wild Type Cohort
arm group label: Arm 2: PIK3CA Mutant Type Cohort
arm group label: Arm 3: Endocrine Resistant Cohort
other name: Arimidex®
intervention type: Drug
intervention name: Goserelin
arm group label: Arm 1: PIK3CA Wild Type Cohort
arm group label: Arm 2: PIK3CA Mutant Type Cohort
arm group label: Arm 3: Endocrine Resistant Cohort
other name: Zoladex®
other name: Decapeptide I
intervention type: Procedure
intervention name: Surgery (standard of care)
description: -Breast and axillary lymph node surgery
arm group label: Arm 1: PIK3CA Wild Type Cohort
arm group label: Arm 2: PIK3CA Mutant Type Cohort
arm group label: Arm 3: Endocrine Resistant Cohort
intervention type: Procedure
intervention name: Tumor biopsy
arm group label: Arm 1: PIK3CA Wild Type Cohort
arm group label: Arm 2: PIK3CA Mutant Type Cohort
arm group label: Arm 3: Endocrine Resistant Cohort
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Cynthia X Ma, M.D., Ph.D.
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.siteman.wustl.edu
description: Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Anastrozole
mesh term: Goserelin
mesh term: Palbociclib
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 