Abstract OT-20-01: Genetic testing for all breast cancer patients (get facts)
Authors: Weiss Anna , Braun Danielle , Stopfer Jill , Desantis Daniel , Dwan Meaghan , Davis Dillon , Jha Anjali , Dominici Laura , Rosenberg Shoshana , King Tari A. , Mittendorf Elizabeth A , Golshan Mehra , Rana Huma Q , Garber Judy E 
Published: February 2021

Abstract
Background: There is evidence that increases in germline cancer genetic testing result in higher rates of contralateral prophylactic mastectomy (CPM) in newly diagnosed breast cancer (BC) patients, even among those with negative results. Unlike carriers of BRCA pathogenic variants (PV), the risks of contralateral breast cancer (CBC) and benefits of CPM for women with PV in moderate penetrance genes are not well studied. There is a critical need to determine how to best counsel BC patients about their personal CBC risk and surgical decisions.
Trial design: Newly diagnosed BC patients are randomized 1:1 to quantitative or standard post-genetic test cancer risk counseling methods by genetic counselors. Quantitative counseling includes personalized CBC risk estimates. For patients with a PV in a BC risk gene, CBC risk estimates are calculated via the “ASK2ME” decision tool (https://ask2me.org/). For those without a BC-associated PV, CBC risk estimates are calculated via a validated model “CBCRisk” (https://cbc-predictor-utd.shinyapps.io/CBCRisk/).Standard counseling does not typically include specific CBC risk estimates.Eligibility criteria: All patients over 18 with newly diagnosed invasive or in situ unilateral BC considering genetic testing at Dana-Farber/Brigham and Women’s Cancer Center are eligible. Exclusion criteria include a diagnosis of previous BC, metastatic or bilateral BC, hematologic malignancy, prior or active other malignancy, prior multi-gene panel testing, known medical or surgical contraindication to surgery and/or CPM.Specific aims: The primary aims are to 1) compare changes in patients’ personal CBC risk assessment before/after quantitative versus standard counseling; 2) determine changes in patients’ propensity to choose CPM before/after quantitative versus standard counseling. The secondary aims are to: 1) compare CPM rates; 2) determine concordance between patient and surgeon assessment of CBC risk; 3) evaluate patient genetic testing satisfaction via the Genetic Testing Satisfaction Survey administered post-counseling; 4) measure patient anxiety via the PROMIS Anxiety Survey administered pre- and post-counseling, at 6 months and 2 years; and 5) measure patient decisional regret for both undergoing genetic testing and their surgery choices at 6 months and 2 years; all by quantitative versus standard counseling arms.
Statistical methods: For aim 1, the difference between patients’ reported personal CBC risk and true risk before and after counseling will be determined. True risk will be based on the ASK2ME/CBCRisk estimates. We hypothesize that the difference between the true and estimated risk will be smaller post-counseling, and smaller in the quantitative counseling versus standard arm. Assuming an expected difference of 5% and expected standard deviation of 20%, 199 patients are needed for each arm to achieve 80% power and type I error of 5% (based on a two-sample t-test). For aim 2, to determine propensity to undergo CPM, patient responses will be assigned a numeric value: Very Unlikely (1), Somewhat unlikely (2), Unsure (3), Somewhat likely (4), Very likely (5). For each patient we will then calculate the difference in scores before/after counseling. Our hypothesis is that differences will be greater in the quantitative arm. Assuming an expected difference of 0.8 and expected standard deviation of 3, 175 patients are needed for each arm to achieve 80% power and type I error rate of 5% (based on a two-sample t-test).
Accrual: Recruitment began on June 8, 2020; there are currently 9 of the target 450 patients enrolled.
Funding Support: Sponsored Research Agreement with Myriad Laboratories, Inc. and a Brigham and Women’s Hospital Department of Surgery Robert T. Osteen Junior Fellowship Award.
PI: Anna Weiss, aweiss5@bwh.harvard.edu, @DrAnnaWeiss
Citation Format: Anna Weiss, Danielle Braun, Jill Stopfer, Daniel Desantis, Meaghan Dwan, Dillon Davis, Anjali Jha, Laura Dominici, Shoshana Rosenberg, Tari A. King, Elizabeth A Mittendorf, Mehra Golshan, Huma Q Rana, Judy E Garber. Genetic testing for all breast cancer patients (get facts) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-20-01.