<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/NCT02209857</url>
  </required_header>
  <id_info>
    <org_study_id>DIAK-TrA-20121</org_study_id>
    <nct_id>NCT02209857</nct_id>
  </id_info>
  <brief_title>The Symphony Triple A Study: Using Symphony in Treatment Decisions Concerning Adjuvant Systemic Therapy</brief_title>
  <acronym>Symphony</acronym>
  <official_title>The Symphony Triple A Study: Using Symphony as an Adjunct to Histopathologic Parameters When the Doctor is Ambivalent About the Administration and Type of Adjunctive Systemic Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Diakonessenhuis, Utrecht</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Agendia</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Diakonessenhuis, Utrecht</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rationale:&#xD;
&#xD;
      Prediction of prognosis in patients with breast cancer is important to determine the&#xD;
      indication for adjuvant chemo-, endocrine- and immunotherapy. Apart from the&#xD;
      clinicopathological parameters incorporated into the Adjuvant!Online predictive model, the&#xD;
      validated 70-gene signature MammaPrint® is predictive of outcome too. MammaPrint® is advised&#xD;
      in the current Dutch CBO guideline (2012) for hormone receptor positive, invasive ductal&#xD;
      breast cancer in individual cases when there is 'doubt' about the indication for adjuvant&#xD;
      chemotherapy based on traditional prognostic factors. In the present study MammaPrint® is&#xD;
      used in this CBO 2012 guideline defined group of patients as an additional test for&#xD;
      decision-making for adjuvant chemotherapy.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To assess the impact of MammaPrint® on clinical decision making regarding the administration&#xD;
      of adjuvant chemotherapy in the CBO 2012 guideline defined group of hormone receptor positive&#xD;
      invasive ductal carcinoma patients when there is doubt about the indication for adjuvant&#xD;
      chemotherapy based on traditional prognostic factors. The influence of various factors and&#xD;
      the impact of MammaPrint® in predefined subgroups will be analyzed too. Data from a national&#xD;
      registry regarding adjuvant systemic treatment in patients with similar clinicopathological&#xD;
      characteristics in whom MammaPrint® was not used will be obtained to provide a control group.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      In the group of patients where national guidelines advocate using systemic therapy but&#xD;
      doctors are ambivalent in treating patients with adjuvant chemotherapy, it is hypothesized&#xD;
      that using MammaPrint® as an additional test will change the indication for adjuvant therapy&#xD;
      in a substantial proportion of patients resulting in at least 10% less patients who receive&#xD;
      adjuvant chemotherapy. Thus, in the study group at least 10% less patients will receive&#xD;
      chemotherapy when compared to a contemporary group of patients with similar&#xD;
      clinicopathological characteristics but without using MammaPrint®&#xD;
&#xD;
      Study population:&#xD;
&#xD;
      Hormone receptor positive, invasive ductal breast cancer patients when there is doubt about&#xD;
      the indication for adjuvant chemotherapy based on traditional prognostic factors.&#xD;
&#xD;
      Study design:&#xD;
&#xD;
      This is a prospective multicentre impact study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. INTRODUCTION AND SCOPE During the last decade treatment guidelines for the&#xD;
           administration of adjuvant chemotherapy in patients with breast cancer have changed,&#xD;
           today advising chemotherapy in the majority of patients having a &gt;1cm invasive cancer.&#xD;
           Prognostic factors used to determine the need for adjuvant chemotherapy are axillary&#xD;
           lymph node status, tumour size and grade, patients' age, and HER2 over expression. In&#xD;
           addition, HER2 status and ER/PR are also predictive of the effect of particular adjuvant&#xD;
           systemic therapies.&#xD;
&#xD;
           Besides predictive models based on histopathologic factors, gene expression arrays have&#xD;
           recognized four different molecular subtypes of breast cancer (Luminal A, Luminal B HER2&#xD;
           +, Luminal B HER2 - and Triple negative). In addition, a number of gene expression&#xD;
           profiles have been designed and validated in its capacity to predict the risk of&#xD;
           dissemination. One of the gene expression profiles is the 70-gene MammaPrint® signature.&#xD;
           The 70-gene MammaPrint® has been validated in different retrospective studies, and in a&#xD;
           prospective community-based feasibility study (RASTER). A considerable discrepancy in&#xD;
           risk estimations among different clinicopathologic guidelines and MammaPrint was&#xD;
           observed. In the RASTER study, addition of MammaPrint to standard clinic-pathological&#xD;
           factors led to a change in adjuvant systemic treatment advice in 19% of patients. The&#xD;
           5-year metastases free survival rates for MammaPrint Low Risk (n=219) and High Risk&#xD;
           (n=208) patients were 97,0% and 91,7%.&#xD;
&#xD;
           The recent Dutch CBO guideline (2012) for breast cancer suggests using validated gene&#xD;
           expression profiles in individual cases in patients with an invasive ductal carcinoma&#xD;
           with positive hormonal receptor when there is doubt about the indication for adjuvant&#xD;
           chemotherapy based on the traditional prognostic factors.&#xD;
&#xD;
        2. OBJECTIVES Primary objectives Assess the impact of MammaPrint® on clinical decision&#xD;
           making regarding the administration of adjuvant chemotherapy in the CBO 2012 guideline&#xD;
           defined group of hormone receptor positive invasive ductal carcinoma patients when there&#xD;
           is doubt about the indication for adjuvant chemotherapy based on traditional prognostic&#xD;
           factors.&#xD;
&#xD;
           Secondary objectives&#xD;
&#xD;
             -  To document the influence of primary tumour characteristics (size, Bloom and&#xD;
                malignancy grade and Her-2 status) and N-status (N0 vs N1mi) with respect to the&#xD;
                (Mammaprint-dependent) decision to give adjuvant chemotherapy in predefined&#xD;
                subgroups&#xD;
&#xD;
             -  To address doctor and patient influence on the eventual decision to give adjuvant&#xD;
                chemotherapy.&#xD;
&#xD;
           Hypothesis In the group of patients where contemporary national guidelines advocate&#xD;
           using systemic therapy but doctors are ambivalent in treating patients with adjuvant&#xD;
           chemotherapy, it is hypothesized that using MammaPrint® as an additional test will&#xD;
           change the indication for adjuvant therapy in a substantial proportion of patients&#xD;
           resulting in at least 10% less patients who receive adjuvant chemotherapy. Thus, in the&#xD;
           study group at least 10% less patients will receive chemotherapy when compared to a&#xD;
           contemporary group of patients with similar clinicopathological characteristics but&#xD;
           without using MammaPrint®&#xD;
&#xD;
        3. STUDY POPULATION&#xD;
&#xD;
           Population (base) The study population is the CBO 2012 guideline defined group of&#xD;
           hormone receptor positive, invasive ductal breast cancer patients when there is doubt&#xD;
           about the indication for adjuvant chemotherapy based on traditional prognostic factors.&#xD;
&#xD;
           Doubt about the indication for adjuvant chemotherapy based on traditional prognostic&#xD;
           factors is an ill-defined criterion. Potential differences in the individual judgement&#xD;
           of medical oncologists deciding on adjuvant systemic therapy are conceivable, which will&#xD;
           translate in differences in the tendency to use MammaPrint®. Based on the CBO-guideline&#xD;
           2012, we expect that the tendency to use MammaPrint® in small, low-grade tumours as well&#xD;
           as in patients with lymph node macrometastases will be relatively low.&#xD;
&#xD;
           Based on the aforementioned assumptions the expected proportional composition of the&#xD;
           study group 'of hormone receptor positive, invasive ductal breast cancer patients when&#xD;
           there is doubt about the indication for adjuvant chemotherapy based on traditional&#xD;
           prognostic factors' is as follows:&#xD;
&#xD;
           N0, BR 1, &gt; 2 cm : 10-15% (60-90 patients) N0, BR 2, &gt; 1 cm : 50-60% (300-350 patients)&#xD;
           N1mi, grade 1,2 : 15-20% (90-120 patients)&#xD;
&#xD;
           Her+, N0, &lt;2c, grade I: &lt;5% (&lt;30 patients) NI: &lt;5% (&lt;30 patients) N0, BR 1, 1-2 cm: &lt;5%&#xD;
           (&lt;30 patients)&#xD;
&#xD;
           Control group&#xD;
&#xD;
           For comparison, data regarding adjuvant chemotherapy in patients in whom no MammaPrint®&#xD;
           was used will be obtained from a national registry Netherlands Cancer Registry (NKR) and&#xD;
           matched with the MammaPrint® group to date of diagnosis and clinicopathological&#xD;
           characteristics. The control group will enable analysis of the impact of Mammaprint on&#xD;
           the proportion of patients receiving adjuvant chemotherapy.&#xD;
&#xD;
        4. STUDY DESIGN&#xD;
&#xD;
      This is a prospective multicentre impact study of MammaPrint® on clinical decision making in&#xD;
      a predefined group of patients where doctors and patients are ambivalent about adjuvant&#xD;
      chemotherapy. MammaPrint® is offered in addition to standard histopathology tests for&#xD;
      decision-making regarding adjuvant systemic therapy. The advised adjuvant systemic therapy&#xD;
      will be recorded before and after disclosure of the MammaPrint® result.&#xD;
&#xD;
      Logistical planning:&#xD;
&#xD;
      Post-surgery:&#xD;
&#xD;
        1. Every patient is discussed in a multidisciplinary team meeting for further treatment&#xD;
           advice. After definitive pathological assessment of tumour size, Bloom and Richardson&#xD;
           grade, confirmation of ER/PR- and HER2 status, potential inclusion of a patient is&#xD;
           assessed.&#xD;
&#xD;
        2. In the surgical outpatient clinic, patients are seen postoperatively and the&#xD;
           histopathological results are discussed. The surgeon informs the patient about the&#xD;
           conclusion of the multidisciplinary team and the patient is informed about existing&#xD;
           uncertainty of adjuvant treatment and the added value of the MammaPrint. Study&#xD;
           information is supplied including an Informed Consent form.&#xD;
&#xD;
        3. The pathologist sends the MammaPrint kit to Agendia for analyses. The attending surgeon&#xD;
           and/or research nurse register patients by completing electronic Case Report Form (CRF)&#xD;
           1.&#xD;
&#xD;
        4. MammaPrint® result is emailed to the surgeon, medical oncologist and mammacare nurse&#xD;
           within 10 working days.&#xD;
&#xD;
        5. Within two weeks the patient is seen in the outpatient clinic by the oncologist to&#xD;
           discuss the result of the MammaPrint®. A final decision concerning adjuvant chemotherapy&#xD;
           is made with the patient. CRF 2 is completed by the oncologist.&#xD;
&#xD;
      The study is expected to enrol 600 patients in approximately 25 hospitals in two and a half&#xD;
      years. The follow up regarding the advice of adjuvant treatment is estimated to be two&#xD;
      months, just after the start of the adjuvant chemotherapy.&#xD;
&#xD;
      5. TISSUE COLLECTION AND 'CLASSIC' HISTOPATHOLOGICAL EXAMINATION&#xD;
&#xD;
      After patients' approval and signed consent forms, samples can be sent to Agendia for&#xD;
      MammaPrint® analysis. The tissue specimen for MammaPrint® analysis consists of a tumour block&#xD;
      or 10 unstained slides with 5µm section on each slide. The tissue can be shipped as formalin&#xD;
      fixed paraffin embedded (FFPE) tissue.&#xD;
&#xD;
      6. STATISTICAL ANALYSIS&#xD;
&#xD;
      Descriptive statistics The primary endpoint is defined as the group of patients who receive&#xD;
      adjuvant systemic therapy and will be compared to the proportion of patients who were advised&#xD;
      to receive chemotherapy before knowledge of the MammaPrint® result. In addition, using&#xD;
      NKR/NBCA data as controls, the absolute difference in the proportion of patients receiving&#xD;
      adjuvant chemotherapy is evaluated. This absolute difference is evaluated for the whole group&#xD;
      as well as for the three expectedly largest subgroups.&#xD;
&#xD;
      Statistical analysis Baseline characteristics will be summarized by an incidence table. The&#xD;
      frequency of chemotherapy + endocrine versus endocrine alone decisions will be addressed&#xD;
      before and after receiving the MammaPrint result in the study group. A McNemars test will be&#xD;
      performed for the comparison of the two proportions treated (before and after), both&#xD;
      expressed as a percentage. When the p- value for this McNemars test is less than 0.05, the&#xD;
      conclusion will be that the two proportions indeed differ significantly.&#xD;
&#xD;
      Chi-square tests (binary variables), non-parametric Mann-Whitney test (for continuous&#xD;
      variables - 2 groups) and non-parametric Kruskall-Wallis tests (continuous variables - more&#xD;
      groups) will be used for the comparison of population characteristics in different subgroups.&#xD;
      When the p- values are less than 0.05, the conclusion will be that there is a significant&#xD;
      difference between the subgroups for these variables.&#xD;
&#xD;
      The percentage treatment change will be calculated for the whole study group and for the&#xD;
      three predefined subgroups. The distribution of MammaPrint test results will be summarized in&#xD;
      a frequency table. With a predefined sample size for the whole group (n=600), and a control&#xD;
      group consisting of at least 1800 patients the minimal detectable difference in the&#xD;
      proportion of patients receiving chemotherapy is 6.6% for the whole group and 9.3% for a&#xD;
      subgroup of 300 patients (2-sided alpha 0.05, Power 80). After inclusion of the first 150&#xD;
      patients, additional sample size calculation will be conducted based on the actual&#xD;
      proportions of the subgroups.&#xD;
&#xD;
      7. ETHICAL CONSIDERATIONS&#xD;
&#xD;
      Regulation statement This study is conducted according to the principles of the Declaration&#xD;
      of Helsinki (version 6, February 2008) and in accordance with the Medical Research Involving&#xD;
      Human Subjects Act (WMO) and other legal and regulatory frameworks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">May 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of adjuvant chemotherapy</measure>
    <time_frame>Within one month after surgery</time_frame>
    <description>We will measure and compare the proportion of patients receiving adjuvant chemotherapy in the group of patients receiving MammaPrint and the group who doesn't receive MammaPrint. In addition we'll record the type of chemotherapy given.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in adjuvant systemic treatment decisions due to MammaPrint use</measure>
    <time_frame>Within one month after (initial) surgery</time_frame>
    <description>The percentage treatment change will be calculated for the whole study group and for the three predefined subgroups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Influence of BluePrint and TargetPrint on adjuvant systemic treatment decisions</measure>
    <time_frame>Within one month after (initial) surgery</time_frame>
    <description>The percentage of adjuvant systemic treatment changes due to the use of BluePrint and/or TargetPrint for the whole studygroup, and the various subgroups will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical utility of MammaPrint in multicentric/contralateral disease.</measure>
    <time_frame>Within one month after (initial) surgery</time_frame>
    <description>Of patients included in the Symphony Triple A study with multicentric or contralateral breast cancer two tissue samples will be collected and a MammaPrint will be performed on both samples. In this subgroup of patients, MammaPrint, BluePrint and TargetPrint results of both tumors will be compared to evaluate the clinical utility of MammaPrint in multicentric and contralateral disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concordance of TargetPrint results with locally assessed ICH/FISH ER, PR and Her2 results</measure>
    <time_frame>Within one month after (initial) surgery</time_frame>
    <description>The concordance between the ER, PR and Her2 results as assessed by the TargetPrint and local ICH/FISH techniques will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of clinical subtype with BluePrint molecular subtype</measure>
    <time_frame>Within one month after (initial) surgery</time_frame>
    <description>Based on the ER, PR and Her2 results as assessed by local pathologist patients can be categorized in clinical molecular subtypes. Concordance between these clinical subtypes and the molecular subtype as assessed by the BluePrint will be assessed</description>
  </secondary_outcome>
  <enrollment type="Actual">660</enrollment>
  <condition>Breastcancer</condition>
  <condition>Invasive Breast Carcinoma by Gene Expression Profile</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      The tissue specimen for MammaPrint® analysis consists of a tumour block or 10 unstained&#xD;
      slides with 5µm section on each slide. The tissue can be shipped as formalin fixed paraffin&#xD;
      embedded (FFPE) tissue. For further information: www.agendia.com or www.symphonytripleA.nl.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The study population is the CBO 2012 guideline defined group of hormone receptor positive,&#xD;
        invasive ductal breast cancer patients when there is doubt about the indication for&#xD;
        adjuvant chemotherapy based on traditional prognostic factors. Patients are included and&#xD;
        MammaPrint® is determined after complete histological assessment following definitive&#xD;
        surgery. The following pathology items have to be recorded: tumour size, grade, ER- and PR-&#xD;
        receptor status, Her-2 neu status, and lymph node status. No difference is made in ethnical&#xD;
        background or past medical history other than cancer.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          -  Oestrogen receptor positive, invasive ductal and female breast cancer patients where&#xD;
             the benefit of adjuvant chemotherapy is uncertain based on traditional prognostic&#xD;
             factors&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Patients with multicentric or contralateral disease&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  Patients with a previous history of malignancy (in the five years before breast cancer&#xD;
             diagnosis), excluding basal cell carcinoma.&#xD;
&#xD;
          -  Patients with confirmed distant metastasis.&#xD;
&#xD;
          -  Patients who undergo neoadjuvant systemic treatment.&#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>Thijs van Dalen, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Diakonessenhuis Utrecht, The Netherlands</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Jeroen Bosch ziekenhuis</name>
      <address>
        <city>Den Bosch</city>
        <state>Brabant</state>
        <zip>5301EH</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Whilhelmina ziekenhuis</name>
      <address>
        <city>Assen</city>
        <state>Drenthe</state>
        <zip>9041RK</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medisch Centrum Zuiderzee</name>
      <address>
        <city>Lelystad</city>
        <state>Flevoland</state>
        <zip>8233AA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nij Smellinghe ziekenhuis</name>
      <address>
        <city>Drachten</city>
        <state>Friesland</state>
        <zip>9202 NN</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tjongerschans</name>
      <address>
        <city>Heerenveen</city>
        <state>Friesland</state>
        <zip>8441PW</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Antoniusziekenhuis</name>
      <address>
        <city>Sneek</city>
        <state>Friesland</state>
        <zip>8601ZK</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gelre ziekenhuis</name>
      <address>
        <city>Apeldoorn</city>
        <state>Gelderland</state>
        <zip>7334 DZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rijnstate</name>
      <address>
        <city>Arnhem</city>
        <state>Gelderland</state>
        <zip>6815AD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gederse Vallei</name>
      <address>
        <city>Ede</city>
        <state>Gelderland</state>
        <zip>6716RP</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sint Jansdal</name>
      <address>
        <city>Harderwijk</city>
        <state>Gelderland</state>
        <zip>3844DG</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ziekenhuis Rivierenland</name>
      <address>
        <city>Tiel</city>
        <state>Gelderland</state>
        <zip>4000 HA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gelre ziekenhuis</name>
      <address>
        <city>Zutphen</city>
        <state>Gelderland</state>
        <zip>7207 AE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medisch Centrum Alkmaar</name>
      <address>
        <city>Alkmaar</city>
        <state>Noord-Holland</state>
        <zip>1815JD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boven IJ ziekenhuis</name>
      <address>
        <city>Amsterdam</city>
        <state>Noord-Holland</state>
        <zip>1034CS</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Onze Lieve Vrouwe Gasthuis</name>
      <address>
        <city>Amsterdam</city>
        <state>Noord-Holland</state>
        <zip>1091AC</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gemini ziekenhuis</name>
      <address>
        <city>Den Helder</city>
        <state>Noord-Holland</state>
        <zip>1782GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kennemer Gasthuis</name>
      <address>
        <city>Haarlem</city>
        <state>Noord-Holland</state>
        <zip>2035RC</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spaarne ziekenhuis</name>
      <address>
        <city>Hoofddorp</city>
        <state>Noord-Holland</state>
        <zip>2134TM</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westfriesgasthuis</name>
      <address>
        <city>Hoorn</city>
        <state>Noord-Holland</state>
        <zip>1624NP</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Waterland ziekenhuis</name>
      <address>
        <city>Purmerend</city>
        <state>Noord-Holland</state>
        <zip>1441RN</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vlietland ziekenhuis</name>
      <address>
        <city>Schiedam</city>
        <state>Noord-Holland</state>
        <zip>3118 JH</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zaans medisch centrum</name>
      <address>
        <city>Zaandam</city>
        <state>Noord-Holland</state>
        <zip>1502DV</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Deventer ziekenhuis</name>
      <address>
        <city>Deventer</city>
        <state>Overijssel</state>
        <zip>7416SE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ropcke Zweers ziekenhuis</name>
      <address>
        <city>Hardenberg</city>
        <state>Overijssel</state>
        <zip>7772SE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Isale klinieken</name>
      <address>
        <city>Zwolle</city>
        <state>Overijssel</state>
        <zip>8011 JW</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alexander Monro ziekenhuis</name>
      <address>
        <city>Bilthoven</city>
        <state>Utrecht</state>
        <zip>3723 MB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ter Gooi ziekenhuis</name>
      <address>
        <city>Hilversum</city>
        <state>Utrecht</state>
        <zip>1201 DA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sint Antoniusziekenhuis</name>
      <address>
        <city>Nieuwegein</city>
        <state>Utrecht</state>
        <zip>3435CM</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zuwe Hofpoort ziekenhuis</name>
      <address>
        <city>Woerden</city>
        <state>Utrecht</state>
        <zip>3447GN</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IJsselland ziekenhuis</name>
      <address>
        <city>Capelle aan den IJssel</city>
        <state>Zuid-Holland</state>
        <zip>2906ZC</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sint Fransiscus gasthuis</name>
      <address>
        <city>Rotterdam</city>
        <state>Zuid-Holland</state>
        <zip>3045 PM</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lange Land ziekenhuis</name>
      <address>
        <city>Zoetermeer</city>
        <state>Zuid-Holland</state>
        <zip>2700 KJ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Martini ziekenhuis</name>
      <address>
        <city>Groningen</city>
        <zip>9728NT</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Diakonessenziekenhuis</name>
      <address>
        <city>Utrecht</city>
        <zip>3508 TG</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <link>
    <url>http://www.agendia.com//</url>
    <description>Information concerning the MammaPrint 70-gene expression profile</description>
  </link>
  <link>
    <url>http://www.oncoline.nl/mammacarcinoom</url>
    <description>Current Dutch national guideline breast cancer</description>
  </link>
  <reference>
    <citation>Ravdin PM, Siminoff LA, Davis GJ, Mercer MB, Hewlett J, Gerson N, Parker HL. Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol. 2001 Feb 15;19(4):980-91. doi: 10.1200/JCO.2001.19.4.980.</citation>
    <PMID>11181660</PMID>
  </reference>
  <reference>
    <citation>Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D. Molecular portraits of human breast tumours. Nature. 2000 Aug 17;406(6797):747-52. doi: 10.1038/35021093.</citation>
    <PMID>10963602</PMID>
  </reference>
  <reference>
    <citation>van de Vijver MJ, He YD, van't Veer LJ, Dai H, Hart AA, Voskuil DW, Schreiber GJ, Peterse JL, Roberts C, Marton MJ, Parrish M, Atsma D, Witteveen A, Glas A, Delahaye L, van der Velde T, Bartelink H, Rodenhuis S, Rutgers ET, Friend SH, Bernards R. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002 Dec 19;347(25):1999-2009. doi: 10.1056/NEJMoa021967.</citation>
    <PMID>12490681</PMID>
  </reference>
  <reference>
    <citation>van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002 Jan 31;415(6871):530-6. doi: 10.1038/415530a.</citation>
    <PMID>11823860</PMID>
  </reference>
  <reference>
    <citation>Buyse M, Loi S, van't Veer L, Viale G, Delorenzi M, Glas AM, d'Assignies MS, Bergh J, Lidereau R, Ellis P, Harris A, Bogaerts J, Therasse P, Floore A, Amakrane M, Piette F, Rutgers E, Sotiriou C, Cardoso F, Piccart MJ; TRANSBIG Consortium. Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst. 2006 Sep 6;98(17):1183-92. doi: 10.1093/jnci/djj329.</citation>
    <PMID>16954471</PMID>
  </reference>
  <reference>
    <citation>Bueno-de-Mesquita JM, Linn SC, Keijzer R, Wesseling J, Nuyten DS, van Krimpen C, Meijers C, de Graaf PW, Bos MM, Hart AA, Rutgers EJ, Peterse JL, Halfwerk H, de Groot R, Pronk A, Floore AN, Glas AM, Van't Veer LJ, van de Vijver MJ. Validation of 70-gene prognosis signature in node-negative breast cancer. Breast Cancer Res Treat. 2009 Oct;117(3):483-95. doi: 10.1007/s10549-008-0191-2. Epub 2008 Sep 26.</citation>
    <PMID>18819002</PMID>
  </reference>
  <reference>
    <citation>Mook S, Schmidt MK, Viale G, Pruneri G, Eekhout I, Floore A, Glas AM, Bogaerts J, Cardoso F, Piccart-Gebhart MJ, Rutgers ET, Van't Veer LJ; TRANSBIG Consortium. The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1-3 positive lymph nodes in an independent validation study. Breast Cancer Res Treat. 2009 Jul;116(2):295-302. doi: 10.1007/s10549-008-0130-2. Epub 2008 Jul 27.</citation>
    <PMID>18661261</PMID>
  </reference>
  <reference>
    <citation>Knauer M, Mook S, Rutgers EJ, Bender RA, Hauptmann M, van de Vijver MJ, Koornstra RH, Bueno-de-Mesquita JM, Linn SC, van 't Veer LJ. The predictive value of the 70-gene signature for adjuvant chemotherapy in early breast cancer. Breast Cancer Res Treat. 2010 Apr;120(3):655-61. doi: 10.1007/s10549-010-0814-2. Epub 2010 Mar 5.</citation>
    <PMID>20204499</PMID>
  </reference>
  <reference>
    <citation>Mook S, Schmidt MK, Weigelt B, Kreike B, Eekhout I, van de Vijver MJ, Glas AM, Floore A, Rutgers EJT, van 't Veer LJ. The 70-gene prognosis signature predicts early metastasis in breast cancer patients between 55 and 70 years of age. Ann Oncol. 2010 Apr;21(4):717-722. doi: 10.1093/annonc/mdp388. Epub 2009 Oct 13.</citation>
    <PMID>19825882</PMID>
  </reference>
  <reference>
    <citation>Mook S, Knauer M, Bueno-de-Mesquita JM, Retel VP, Wesseling J, Linn SC, Van't Veer LJ, Rutgers EJ. Metastatic potential of T1 breast cancer can be predicted by the 70-gene MammaPrint signature. Ann Surg Oncol. 2010 May;17(5):1406-13. doi: 10.1245/s10434-009-0902-x. Epub 2010 Jan 22.</citation>
    <PMID>20094918</PMID>
  </reference>
  <reference>
    <citation>Bueno-de-Mesquita JM, van Harten WH, Retel VP, van 't Veer LJ, van Dam FS, Karsenberg K, Douma KF, van Tinteren H, Peterse JL, Wesseling J, Wu TS, Atsma D, Rutgers EJ, Brink G, Floore AN, Glas AM, Roumen RM, Bellot FE, van Krimpen C, Rodenhuis S, van de Vijver MJ, Linn SC. Use of 70-gene signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER). Lancet Oncol. 2007 Dec;8(12):1079-1087. doi: 10.1016/S1470-2045(07)70346-7. Epub 2007 Nov 26. Erratum In: Lancet Oncol. 2008 Jan;9(1):10.</citation>
    <PMID>18042430</PMID>
  </reference>
  <reference>
    <citation>Drukker CA, Bueno-de-Mesquita JM, Retel VP, van Harten WH, van Tinteren H, Wesseling J, Roumen RM, Knauer M, van 't Veer LJ, Sonke GS, Rutgers EJ, van de Vijver MJ, Linn SC. A prospective evaluation of a breast cancer prognosis signature in the observational RASTER study. Int J Cancer. 2013 Aug 15;133(4):929-36. doi: 10.1002/ijc.28082. Epub 2013 Mar 4.</citation>
    <PMID>23371464</PMID>
  </reference>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>August 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 6, 2014</study_first_posted>
  <last_update_submitted>February 14, 2017</last_update_submitted>
  <last_update_submitted_qc>February 14, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Breastcancer</keyword>
  <keyword>Adjuvant chemotherapy</keyword>
  <keyword>70-gene expression profile</keyword>
  <keyword>MammaPrint</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02209857
org study id: DIAK-TrA-20121
nct id: NCT02209857
lead sponsor: 
collaborator: 
has dmc: No
Rationale:

      Prediction of prognosis in patients with breast cancer is important to determine the
      indication for adjuvant chemo-, endocrine- and immunotherapy. Apart from the
      clinicopathological parameters incorporated into the Adjuvant!Online predictive model, the
      validated 70-gene signature MammaPrint® is predictive of outcome too. MammaPrint® is advised
      in the current Dutch CBO guideline (2012) for hormone receptor positive, invasive ductal
      breast cancer in individual cases when there is 'doubt' about the indication for adjuvant
      chemotherapy based on traditional prognostic factors. In the present study MammaPrint® is
      used in this CBO 2012 guideline defined group of patients as an additional test for
      decision-making for adjuvant chemotherapy.

      Objective:

      To assess the impact of MammaPrint® on clinical decision making regarding the administration
      of adjuvant chemotherapy in the CBO 2012 guideline defined group of hormone receptor positive
      invasive ductal carcinoma patients when there is doubt about the indication for adjuvant
      chemotherapy based on traditional prognostic factors. The influence of various factors and
      the impact of MammaPrint® in predefined subgroups will be analyzed too. Data from a national
      registry regarding adjuvant systemic treatment in patients with similar clinicopathological
      characteristics in whom MammaPrint® was not used will be obtained to provide a control group.

      Hypothesis:

      In the group of patients where national guidelines advocate using systemic therapy but
      doctors are ambivalent in treating patients with adjuvant chemotherapy, it is hypothesized
      that using MammaPrint® as an additional test will change the indication for adjuvant therapy
      in a substantial proportion of patients resulting in at least 10% less patients who receive
      adjuvant chemotherapy. Thus, in the study group at least 10% less patients will receive
      chemotherapy when compared to a contemporary group of patients with similar
      clinicopathological characteristics but without using MammaPrint®

      Study population:

      Hormone receptor positive, invasive ductal breast cancer patients when there is doubt about
      the indication for adjuvant chemotherapy based on traditional prognostic factors.

      Study design:

      This is a prospective multicentre impact study.
1. INTRODUCTION AND SCOPE During the last decade treatment guidelines for the
           administration of adjuvant chemotherapy in patients with breast cancer have changed,
           today advising chemotherapy in the majority of patients having a >1cm invasive cancer.
           Prognostic factors used to determine the need for adjuvant chemotherapy are axillary
           lymph node status, tumour size and grade, patients' age, and HER2 over expression. In
           addition, HER2 status and ER/PR are also predictive of the effect of particular adjuvant
           systemic therapies.

           Besides predictive models based on histopathologic factors, gene expression arrays have
           recognized four different molecular subtypes of breast cancer (Luminal A, Luminal B HER2
           +, Luminal B HER2 - and Triple negative). In addition, a number of gene expression
           profiles have been designed and validated in its capacity to predict the risk of
           dissemination. One of the gene expression profiles is the 70-gene MammaPrint® signature.
           The 70-gene MammaPrint® has been validated in different retrospective studies, and in a
           prospective community-based feasibility study (RASTER). A considerable discrepancy in
           risk estimations among different clinicopathologic guidelines and MammaPrint was
           observed. In the RASTER study, addition of MammaPrint to standard clinic-pathological
           factors led to a change in adjuvant systemic treatment advice in 19% of patients. The
           5-year metastases free survival rates for MammaPrint Low Risk (n=219) and High Risk
           (n=208) patients were 97,0% and 91,7%.

           The recent Dutch CBO guideline (2012) for breast cancer suggests using validated gene
           expression profiles in individual cases in patients with an invasive ductal carcinoma
           with positive hormonal receptor when there is doubt about the indication for adjuvant
           chemotherapy based on the traditional prognostic factors.

        2. OBJECTIVES Primary objectives Assess the impact of MammaPrint® on clinical decision
           making regarding the administration of adjuvant chemotherapy in the CBO 2012 guideline
           defined group of hormone receptor positive invasive ductal carcinoma patients when there
           is doubt about the indication for adjuvant chemotherapy based on traditional prognostic
           factors.

           Secondary objectives

             -  To document the influence of primary tumour characteristics (size, Bloom and
                malignancy grade and Her-2 status) and N-status (N0 vs N1mi) with respect to the
                (Mammaprint-dependent) decision to give adjuvant chemotherapy in predefined
                subgroups

             -  To address doctor and patient influence on the eventual decision to give adjuvant
                chemotherapy.

           Hypothesis In the group of patients where contemporary national guidelines advocate
           using systemic therapy but doctors are ambivalent in treating patients with adjuvant
           chemotherapy, it is hypothesized that using MammaPrint® as an additional test will
           change the indication for adjuvant therapy in a substantial proportion of patients
           resulting in at least 10% less patients who receive adjuvant chemotherapy. Thus, in the
           study group at least 10% less patients will receive chemotherapy when compared to a
           contemporary group of patients with similar clinicopathological characteristics but
           without using MammaPrint®

        3. STUDY POPULATION

           Population (base) The study population is the CBO 2012 guideline defined group of
           hormone receptor positive, invasive ductal breast cancer patients when there is doubt
           about the indication for adjuvant chemotherapy based on traditional prognostic factors.

           Doubt about the indication for adjuvant chemotherapy based on traditional prognostic
           factors is an ill-defined criterion. Potential differences in the individual judgement
           of medical oncologists deciding on adjuvant systemic therapy are conceivable, which will
           translate in differences in the tendency to use MammaPrint®. Based on the CBO-guideline
           2012, we expect that the tendency to use MammaPrint® in small, low-grade tumours as well
           as in patients with lymph node macrometastases will be relatively low.

           Based on the aforementioned assumptions the expected proportional composition of the
           study group 'of hormone receptor positive, invasive ductal breast cancer patients when
           there is doubt about the indication for adjuvant chemotherapy based on traditional
           prognostic factors' is as follows:

           N0, BR 1, > 2 cm : 10-15% (60-90 patients) N0, BR 2, > 1 cm : 50-60% (300-350 patients)
           N1mi, grade 1,2 : 15-20% (90-120 patients)

           Her+, N0, <2c, grade I: <5% (<30 patients) NI: <5% (<30 patients) N0, BR 1, 1-2 cm: <5%
           (<30 patients)

           Control group

           For comparison, data regarding adjuvant chemotherapy in patients in whom no MammaPrint®
           was used will be obtained from a national registry Netherlands Cancer Registry (NKR) and
           matched with the MammaPrint® group to date of diagnosis and clinicopathological
           characteristics. The control group will enable analysis of the impact of Mammaprint on
           the proportion of patients receiving adjuvant chemotherapy.

        4. STUDY DESIGN

      This is a prospective multicentre impact study of MammaPrint® on clinical decision making in
      a predefined group of patients where doctors and patients are ambivalent about adjuvant
      chemotherapy. MammaPrint® is offered in addition to standard histopathology tests for
      decision-making regarding adjuvant systemic therapy. The advised adjuvant systemic therapy
      will be recorded before and after disclosure of the MammaPrint® result.

      Logistical planning:

      Post-surgery:

        1. Every patient is discussed in a multidisciplinary team meeting for further treatment
           advice. After definitive pathological assessment of tumour size, Bloom and Richardson
           grade, confirmation of ER/PR- and HER2 status, potential inclusion of a patient is
           assessed.

        2. In the surgical outpatient clinic, patients are seen postoperatively and the
           histopathological results are discussed. The surgeon informs the patient about the
           conclusion of the multidisciplinary team and the patient is informed about existing
           uncertainty of adjuvant treatment and the added value of the MammaPrint. Study
           information is supplied including an Informed Consent form.

        3. The pathologist sends the MammaPrint kit to Agendia for analyses. The attending surgeon
           and/or research nurse register patients by completing electronic Case Report Form (CRF)
           1.

        4. MammaPrint® result is emailed to the surgeon, medical oncologist and mammacare nurse
           within 10 working days.

        5. Within two weeks the patient is seen in the outpatient clinic by the oncologist to
           discuss the result of the MammaPrint®. A final decision concerning adjuvant chemotherapy
           is made with the patient. CRF 2 is completed by the oncologist.

      The study is expected to enrol 600 patients in approximately 25 hospitals in two and a half
      years. The follow up regarding the advice of adjuvant treatment is estimated to be two
      months, just after the start of the adjuvant chemotherapy.

      5. TISSUE COLLECTION AND 'CLASSIC' HISTOPATHOLOGICAL EXAMINATION

      After patients' approval and signed consent forms, samples can be sent to Agendia for
      MammaPrint® analysis. The tissue specimen for MammaPrint® analysis consists of a tumour block
      or 10 unstained slides with 5µm section on each slide. The tissue can be shipped as formalin
      fixed paraffin embedded (FFPE) tissue.

      6. STATISTICAL ANALYSIS

      Descriptive statistics The primary endpoint is defined as the group of patients who receive
      adjuvant systemic therapy and will be compared to the proportion of patients who were advised
      to receive chemotherapy before knowledge of the MammaPrint® result. In addition, using
      NKR/NBCA data as controls, the absolute difference in the proportion of patients receiving
      adjuvant chemotherapy is evaluated. This absolute difference is evaluated for the whole group
      as well as for the three expectedly largest subgroups.

      Statistical analysis Baseline characteristics will be summarized by an incidence table. The
      frequency of chemotherapy + endocrine versus endocrine alone decisions will be addressed
      before and after receiving the MammaPrint result in the study group. A McNemars test will be
      performed for the comparison of the two proportions treated (before and after), both
      expressed as a percentage. When the p- value for this McNemars test is less than 0.05, the
      conclusion will be that the two proportions indeed differ significantly.

      Chi-square tests (binary variables), non-parametric Mann-Whitney test (for continuous
      variables - 2 groups) and non-parametric Kruskall-Wallis tests (continuous variables - more
      groups) will be used for the comparison of population characteristics in different subgroups.
      When the p- values are less than 0.05, the conclusion will be that there is a significant
      difference between the subgroups for these variables.

      The percentage treatment change will be calculated for the whole study group and for the
      three predefined subgroups. The distribution of MammaPrint test results will be summarized in
      a frequency table. With a predefined sample size for the whole group (n=600), and a control
      group consisting of at least 1800 patients the minimal detectable difference in the
      proportion of patients receiving chemotherapy is 6.6% for the whole group and 9.3% for a
      subgroup of 300 patients (2-sided alpha 0.05, Power 80). After inclusion of the first 150
      patients, additional sample size calculation will be conducted based on the actual
      proportions of the subgroups.

      7. ETHICAL CONSIDERATIONS

      Regulation statement This study is conducted according to the principles of the Declaration
      of Helsinki (version 6, February 2008) and in accordance with the Medical Research Involving
      Human Subjects Act (WMO) and other legal and regulatory frameworks.
observational model: Case-Control
time perspective: Prospective
measure: Frequency of adjuvant chemotherapy
time frame: Within one month after surgery
description: We will measure and compare the proportion of patients receiving adjuvant chemotherapy in the group of patients receiving MammaPrint and the group who doesn't receive MammaPrint. In addition we'll record the type of chemotherapy given.
measure: Changes in adjuvant systemic treatment decisions due to MammaPrint use
time frame: Within one month after (initial) surgery
description: The percentage treatment change will be calculated for the whole study group and for the three predefined subgroups.
measure: Influence of BluePrint and TargetPrint on adjuvant systemic treatment decisions
time frame: Within one month after (initial) surgery
description: The percentage of adjuvant systemic treatment changes due to the use of BluePrint and/or TargetPrint for the whole studygroup, and the various subgroups will be calculated.
measure: Clinical utility of MammaPrint in multicentric/contralateral disease.
time frame: Within one month after (initial) surgery
description: Of patients included in the Symphony Triple A study with multicentric or contralateral breast cancer two tissue samples will be collected and a MammaPrint will be performed on both samples. In this subgroup of patients, MammaPrint, BluePrint and TargetPrint results of both tumors will be compared to evaluate the clinical utility of MammaPrint in multicentric and contralateral disease.
measure: Concordance of TargetPrint results with locally assessed ICH/FISH ER, PR and Her2 results
time frame: Within one month after (initial) surgery
description: The concordance between the ER, PR and Her2 results as assessed by the TargetPrint and local ICH/FISH techniques will be assessed.
measure: Comparison of clinical subtype with BluePrint molecular subtype
time frame: Within one month after (initial) surgery
description: Based on the ER, PR and Her2 results as assessed by local pathologist patients can be categorized in clinical molecular subtypes. Concordance between these clinical subtypes and the molecular subtype as assessed by the BluePrint will be assessed
The tissue specimen for MammaPrint® analysis consists of a tumour block or 10 unstained
      slides with 5µm section on each slide. The tissue can be shipped as formalin fixed paraffin
      embedded (FFPE) tissue. For further information: www.agendia.com or www.symphonytripleA.nl.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Thijs van Dalen, Dr
role: Principal Investigator
affiliation: Diakonessenhuis Utrecht, The Netherlands
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country: Netherlands
url: http://www.agendia.com//
description: Information concerning the MammaPrint 70-gene expression profile
url: http://www.oncoline.nl/mammacarcinoom
description: Current Dutch national guideline breast cancer
citation: Ravdin PM, Siminoff LA, Davis GJ, Mercer MB, Hewlett J, Gerson N, Parker HL. Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol. 2001 Feb 15;19(4):980-91. doi: 10.1200/JCO.2001.19.4.980.
PMID: 11181660
citation: Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D. Molecular portraits of human breast tumours. Nature. 2000 Aug 17;406(6797):747-52. doi: 10.1038/35021093.
PMID: 10963602
citation: van de Vijver MJ, He YD, van't Veer LJ, Dai H, Hart AA, Voskuil DW, Schreiber GJ, Peterse JL, Roberts C, Marton MJ, Parrish M, Atsma D, Witteveen A, Glas A, Delahaye L, van der Velde T, Bartelink H, Rodenhuis S, Rutgers ET, Friend SH, Bernards R. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002 Dec 19;347(25):1999-2009. doi: 10.1056/NEJMoa021967.
PMID: 12490681
citation: van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002 Jan 31;415(6871):530-6. doi: 10.1038/415530a.
PMID: 11823860
citation: Buyse M, Loi S, van't Veer L, Viale G, Delorenzi M, Glas AM, d'Assignies MS, Bergh J, Lidereau R, Ellis P, Harris A, Bogaerts J, Therasse P, Floore A, Amakrane M, Piette F, Rutgers E, Sotiriou C, Cardoso F, Piccart MJ; TRANSBIG Consortium. Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst. 2006 Sep 6;98(17):1183-92. doi: 10.1093/jnci/djj329.
PMID: 16954471
citation: Bueno-de-Mesquita JM, Linn SC, Keijzer R, Wesseling J, Nuyten DS, van Krimpen C, Meijers C, de Graaf PW, Bos MM, Hart AA, Rutgers EJ, Peterse JL, Halfwerk H, de Groot R, Pronk A, Floore AN, Glas AM, Van't Veer LJ, van de Vijver MJ. Validation of 70-gene prognosis signature in node-negative breast cancer. Breast Cancer Res Treat. 2009 Oct;117(3):483-95. doi: 10.1007/s10549-008-0191-2. Epub 2008 Sep 26.
PMID: 18819002
citation: Mook S, Schmidt MK, Viale G, Pruneri G, Eekhout I, Floore A, Glas AM, Bogaerts J, Cardoso F, Piccart-Gebhart MJ, Rutgers ET, Van't Veer LJ; TRANSBIG Consortium. The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1-3 positive lymph nodes in an independent validation study. Breast Cancer Res Treat. 2009 Jul;116(2):295-302. doi: 10.1007/s10549-008-0130-2. Epub 2008 Jul 27.
PMID: 18661261
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responsible party type: Sponsor
mesh term: Breast Neoplasms