<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/NCT03761420</url>
  </required_header>
  <id_info>
    <org_study_id>2017/1356</org_study_id>
    <nct_id>NCT03761420</nct_id>
  </id_info>
  <brief_title>Adjuvant Endocrine Therapy in Early Stage Breast Cancer: Adherence and Clinical Outcome</brief_title>
  <official_title>Adjuvant Endocrine Therapy in Early Stage Breast Cancer: Impact of Drug Adherence/Persistence on Clinical Outcome in Various Breast Cancer Subtypes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Olavs Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Norwegian University of Science and Technology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>St. Olavs Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Breast cancer is the most common cancer among women in Norway. In 2016, 3402 new cases were&#xD;
      diagnosed (3371 in women). Breast cancer is still the second most common cause of death from&#xD;
      cancer among women with 585 breast cancer deaths in Norway in 2015. The majority of the&#xD;
      patients (70-75 %) belong to the Luminal subtypes, which comprise the hormone receptor&#xD;
      (oestrogen receptor (ER) and/or progesterone receptor (PR)) positive tumours.&#xD;
&#xD;
      The most important systemic adjuvant therapy in luminal breast cancers is a long-lasting&#xD;
      administration of per-oral anti-oestrogen medication. A systemic hypo estrogenic state in the&#xD;
      body may be created by the selective oestrogen receptor modulator tamoxifen or by inhibitors&#xD;
      of the peripheral systemic aromatization of adrenal androgens into estrogens (aromatase&#xD;
      inhibitors). Initially, tamoxifen was given adjuvant for 2 years, later prolonged to 5 years&#xD;
      and recently an extension to 10 years has been recommended for premenopausal women. Aromatase&#xD;
      inhibitors were introduced in Norwegian treatment guidelines in 2002. Currently, they are&#xD;
      recommended in postmenopausal patients for 5 years, either as monotherapy or in concert with&#xD;
      tamoxifen (aromatase inhibitors for 2 years followed by tamoxifen for 3 years).&#xD;
&#xD;
      In premenopausal breast cancer patients, tamoxifen still is the drug of choice. Two of the&#xD;
      major underlying reasons for late recurrences in luminal breast cancer subtypes are&#xD;
      development of endocrine resistance to tamoxifen and aromatase inhibitors or failure of&#xD;
      taking the medication as prescribed. Higher mortality has been shown for breast cancer&#xD;
      patients with reduced tamoxifen adherence. The patients' ability to follow instructions and&#xD;
      recommendations are probably overestimated in controlled trials due to patient selection and&#xD;
      close follow-up in the study setting. Some patients experience distressing side effects like&#xD;
      hot flushes, fatigue, joint pain, mood swings and vaginal dryness. To the investigators'&#xD;
      knowledge, there are few studies in Norway regarding discontinuation of endocrine treatment&#xD;
      in breast cancer. In this study they will investigate the long-term discontinuation pattern&#xD;
      to oral adjuvant systemic endocrine therapy in a large cohort of breast cancer patients&#xD;
      treated in St. Olav's hospital in Trondheim, Norway, and the association between adherence to&#xD;
      endocrine treatment and long-term survival.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After identifying all patients who were recommended endocrine therapy, data will be linked to&#xD;
      the Norwegian Prescription Database (NorPD). Adherence will be estimated based on to which&#xD;
      extent the patients actually have effectuated their prescriptions at Norwegian pharmacies. In&#xD;
      the 5-year long treatment period, the patients receive a prescription refill of tamoxifen or&#xD;
      aromatase inhibitor tablets for a 100 days interval. Medication Possession Ratio (MPR) will&#xD;
      be used as proxy for adherence. The estimations will be performed in the following way: For&#xD;
      each patient, we will receive the total number of pills and the total length of time from&#xD;
      first to latest prescription effectuated. MPR is the number of pills divided by the total&#xD;
      number of days in the time from first prescription to discontinuation. Discontinuation will&#xD;
      be estimated to date for latest effectuation of the prescription plus 100 days (due to the&#xD;
      number of pills prescribed). From these estimations, we will categorize the patients in&#xD;
      groups taking MPR and total period of time into consideration. Taking prescript medication&#xD;
      equal to or more than 80% is considered as adherent (MPR ≥ 80 %). Likewise, non-adherence is&#xD;
      defined as MPR &lt; 80 %.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2019</start_date>
  <completion_date type="Actual">April 1, 2021</completion_date>
  <primary_completion_date type="Actual">April 1, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Medication Possession Ratio (MPR) as a proxy for medication adherence</measure>
    <time_frame>0-5 years after surgery for breast cancer</time_frame>
    <description>see Detailed description</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Survival</measure>
    <time_frame>5-14 years after surgery for breast cancer</time_frame>
    <description>Breast cancer specific survival according to adherence and non-adherence</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">1411</enrollment>
  <condition>Breast Neoplasm</condition>
  <arm_group>
    <arm_group_label>breast cancer postoperative</arm_group_label>
    <description>got surgery for breast cancer in St Olavs Hospital, Trondheim, during 2004-2013</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        breast cancer patients treated (surgery) at St Olavs Hospital in Trondheim, Norway, during&#xD;
        2004-2013.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Luminal breast cancer&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Non-Luminal breast cancer&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anne Irene Hagen, md phd</last_name>
    <role>Study Director</role>
    <affiliation>St. Olavs Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St Olavs Hospital</name>
      <address>
        <city>Trondheim</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>November 28, 2018</study_first_submitted>
  <study_first_submitted_qc>November 30, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 3, 2018</study_first_posted>
  <last_update_submitted>April 30, 2021</last_update_submitted>
  <last_update_submitted_qc>April 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Medication Adherence</keyword>
  <keyword>Antineoplastic Agents, Hormonal</keyword>
  <keyword>Chemotherapy, Adjuvant</keyword>
  <keyword>Treatment Outcome</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/NCT03761420
org study id: 2017/1356
nct id: NCT03761420
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Breast cancer is the most common cancer among women in Norway. In 2016, 3402 new cases were
      diagnosed (3371 in women). Breast cancer is still the second most common cause of death from
      cancer among women with 585 breast cancer deaths in Norway in 2015. The majority of the
      patients (70-75 %) belong to the Luminal subtypes, which comprise the hormone receptor
      (oestrogen receptor (ER) and/or progesterone receptor (PR)) positive tumours.

      The most important systemic adjuvant therapy in luminal breast cancers is a long-lasting
      administration of per-oral anti-oestrogen medication. A systemic hypo estrogenic state in the
      body may be created by the selective oestrogen receptor modulator tamoxifen or by inhibitors
      of the peripheral systemic aromatization of adrenal androgens into estrogens (aromatase
      inhibitors). Initially, tamoxifen was given adjuvant for 2 years, later prolonged to 5 years
      and recently an extension to 10 years has been recommended for premenopausal women. Aromatase
      inhibitors were introduced in Norwegian treatment guidelines in 2002. Currently, they are
      recommended in postmenopausal patients for 5 years, either as monotherapy or in concert with
      tamoxifen (aromatase inhibitors for 2 years followed by tamoxifen for 3 years).

      In premenopausal breast cancer patients, tamoxifen still is the drug of choice. Two of the
      major underlying reasons for late recurrences in luminal breast cancer subtypes are
      development of endocrine resistance to tamoxifen and aromatase inhibitors or failure of
      taking the medication as prescribed. Higher mortality has been shown for breast cancer
      patients with reduced tamoxifen adherence. The patients' ability to follow instructions and
      recommendations are probably overestimated in controlled trials due to patient selection and
      close follow-up in the study setting. Some patients experience distressing side effects like
      hot flushes, fatigue, joint pain, mood swings and vaginal dryness. To the investigators'
      knowledge, there are few studies in Norway regarding discontinuation of endocrine treatment
      in breast cancer. In this study they will investigate the long-term discontinuation pattern
      to oral adjuvant systemic endocrine therapy in a large cohort of breast cancer patients
      treated in St. Olav's hospital in Trondheim, Norway, and the association between adherence to
      endocrine treatment and long-term survival.
After identifying all patients who were recommended endocrine therapy, data will be linked to
      the Norwegian Prescription Database (NorPD). Adherence will be estimated based on to which
      extent the patients actually have effectuated their prescriptions at Norwegian pharmacies. In
      the 5-year long treatment period, the patients receive a prescription refill of tamoxifen or
      aromatase inhibitor tablets for a 100 days interval. Medication Possession Ratio (MPR) will
      be used as proxy for adherence. The estimations will be performed in the following way: For
      each patient, we will receive the total number of pills and the total length of time from
      first to latest prescription effectuated. MPR is the number of pills divided by the total
      number of days in the time from first prescription to discontinuation. Discontinuation will
      be estimated to date for latest effectuation of the prescription plus 100 days (due to the
      number of pills prescribed). From these estimations, we will categorize the patients in
      groups taking MPR and total period of time into consideration. Taking prescript medication
      equal to or more than 80% is considered as adherent (MPR ≥ 80 %). Likewise, non-adherence is
      defined as MPR < 80 %.
observational model: Case-Only
time perspective: Retrospective
measure: Medication Possession Ratio (MPR) as a proxy for medication adherence
time frame: 0-5 years after surgery for breast cancer
description: see Detailed description
measure: Survival
time frame: 5-14 years after surgery for breast cancer
description: Breast cancer specific survival according to adherence and non-adherence
arm group label: breast cancer postoperative
description: got surgery for breast cancer in St Olavs Hospital, Trondheim, during 2004-2013
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 100 Years
healthy volunteers: No
last name: Anne Irene Hagen, md phd
role: Study Director
affiliation: St. Olavs Hospital
facility: 
country: Norway
responsible party type: Sponsor
mesh term: Breast Neoplasms