Clinical trial NCT04474834: Genetic Risk Estimations for Influencing Decision Making in Women at High Risk of Breast Cancer, GENRE 2 Study
Official title: GENetic Risk Estimation of Breast Cancer Prior to Decisions on Preventive Therapy Uptake, Risk Reducing Surgery or Intensive Imaging Surveillance: A Study to Determine if a Polygenic Risk Score Influences the Decision Making Options Amongst High Risk Women (GENRE 2)
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Breast Cancer
Keywords: BCRAT
IBIS
Breast Cancer
BRCA1
BRCA2
BRCA
BRCA 1/2
Tyrer-Cuzick
CEDM
PRS
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2020-07-17
Enrollment: 900
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women attending the Mayo Clinic Breast Cancer clinics in Rochester, Arizona and Florida or the Mayo Clinic Health System in Austin or Albert Lea who meet eligibility criteria will be offered participation in this study after initial clinical calculation of the BCRAT or IBIS score and counseling as to the advisability of preventive therapy.

Brief summary: The primary aim of this study is to determine if the addition of an individual polygenic risk score (PRS) in addition to the Breast Cancer Risk Assessment Tool (BCRAT) or Tyrer-Cuzick (IBIS) score will aid women at risk of breast cancer in making a decision to take (or not take) medications to prevent breast cancer.

Detailed description: This is a minimal risk prospective multisite study with a single arm incorporating the PRS into a standard breast cancer risk reduction consultation, followed by annual surveys over 10 years to determine if and how the availability of the PRS influenced patient decisions regarding preventive medicine and medication compliance. Because women know beforehand that the PRS is pending, study participants will be advised that a final decision to take preventive medicine must be deferred until after the PRS results are made available. Nevertheless, a survey of understanding of risk and benefit and assessment of willingness to take preventive medicine will be done prior to receiving the PRS results and then another survey will be completed after receiving the PRS score.

Eligibility criteria: Inclusion Criteria:

* Women \>= 35 years old and =\< 75 years old with at least one of the following:

  * A National Cancer Institute (NCI)-BCRAT 5 year risk of \>= 3% which corresponds to the level in which there is moderate evidence of treatment benefit outweighing risk according to the United States (US) Preventative Services Task Force
  * IBIS (Tyrer-Cuzik) score for the 10 year risk of breast cancer of \>= 5%
  * History atypical ductal hyperplasia or atypical lobular hyperplasia with a BCRAT \>= 3% or IBIS \>= 5%
  * History of lobular carcinoma in situ with a BCRAT \>= 3% or IBIS \>= 5% OR
* Women \>= 18 years old or =\< 75 years old with a BRCA 1 or 2 mutation, CHEK 2, PALB 2, ATM, or other hereditary breast mutation carrier per investigator
* Willing and able to provide an email address to receive study surveys
* Able to participate in all aspects of the study
* Understand and sign the study informed consent

Exclusion Criteria:

* Women whose BCRAT falls below the threshold (\<3 % 5 year risk) of moderate benefit according to the US Preventative Task Force AND Women whose IBIS score is \<8% for the 10 year risk
* Women with known contra-indications to Tamoxifen, raloxifene ,exemestane, or anastrazole
* Current or prior use of Tamoxifen, raloxifene, exemestane or anastrazole
* Unable to give informed consent
* Prior history of invasive breast cancer, ductal carcinoma in situ or other breast cancers
* At high risk due to prior radiation therapy to the chest
* Women who are pregnant or breastfeeding
* Prior risk reducing or prophylactic mastectomy
* Unwilling or unable to provide an email address for study surveys to be sent to
* Subject has a known history or any condition or factor judged by the investigator to preclude participation in the study or which might hinder adherence

Primary outcomes:
measure: Patient self-reported intention to take a breast cancer preventing medication
timeFrame: up to 6 months after initial consultation
Secondary outcomes:
measure: Proportion of patients who are taking preventative medications each year for 10 years
timeFrame: Each year for up to 10 years
measure: Endocrine related quality of life scores each year for 10 years
timeFrame: Each year for up to 10 years
measure: Proportion of patient who are pursuing supplemental screening for 10 years
timeFrame: Each year for up to 10 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: Mayo Clinic
name: Sandhya Pruthi, MD
role: PRINCIPAL_INVESTIGATOR
References: