Abstract PD10-05: Universal genetic testing in breast cancer patients: A multi-center prospective study
Authors: Ernst Brenda , Ertz-Archambault Natalie , Rhodes Deborah J , Northfelt Donald W , Wick Myra , Riegert-Johnson Douglas L , Okuno Scott , Kunze Katie , Golafshar Michael , Azevedo Cindy M , Junior PLS Uson , Esplin ED , Nussbaum Robert , Klint Margaret , Mantia Sarah , Hager Megan , Stewart Keith , Samadder Niloy Jewel 
Published: February 2021

Background: Hereditary factors play a key role in the risk of developing breast cancers. Identification of a germline predisposition can have important implications for treatment decisions, risk-reducing interventions, cancer screening, and testing for family members. Aim: To determine the prevalence of pathogenic or likely pathogenic germline mutations (P/LP) using a “universal” testing approach and uptake of no-cost cascade family testing in patients with breast cancer. Methods: We undertook a prospective multi-site study of germline genetic alterations among breast cancer patients receiving care at Mayo Clinic cancer centers in Rochester, MN; Eau Claire, WI; Jacksonville, FL and Phoenix, AZ between April 1, 2018 and March 31, 2020. Patients with a new or active breast cancer diagnosis (all stages) irrespective of cancer family history were tested with a &gt;80-gene next generation sequencing panel.Results: Of 390 patients, the median age was 58 years (SD 12.3), 1% were male, 85% were white and 28% had advanced (stage 3-4) disease. P/LP were found in 12.1% (n=47) of patients, including 29 in moderate and high penetrance cancer susceptibility genes. 13 (3.3%) patients had mutations in BRCA1 or 2, while 33 (8.4%) had mutations in BRCAness (ATM, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, CHEK2, NBN, PALB2, RAD50, RAD51C, RAD51D, WRN) associated genes. Of the P/LP findings the most frequent aberrations were in BRCA2 (13.5%), BRCA1 (11.5%), CHEK2 (11.5%), MUTYH (11.5%), and WRN (9.6%). Variants of uncertain significance were found in 209 (53.6%) including 26 (6.6%) with concurrent P/LP and VUS. 37 (9.4%) patients had mutations associated with published management recommendations, precision therapies and/or clinical trial eligibility. 10 (2.6%) patients had P/LP that would not have met current screening guidelines, including 4 with moderate or high penetrance mutations. Patients with younger age of diagnosis were less likely than patients with older age of diagnosis to have a P/LP mutation (OR= 0.47, 95%CI: 0.25-0.90 p = 0.020). Only 10 (21%) patients with P/LP had family members undergo familial site- specific testing at no cost.Conclusions: In this prospective multi-center study of unselected breast cancer patients, universal multi-gene panel testing found that 1 in 8 patients harbor P/LP germline variants. Current guidelines were able to identify the majority of patients with P/LP mutations. Familial site specific testing is greatly under-utilized even when cost is not a barrier. Multigene panels impact cancer patient care by identifying precision medicine treatment interventions, and guiding long-term medical management and preventive surveillance.

Citation Format: Brenda Ernst, Natalie Ertz-Archambault, Deborah J Rhodes, Donald W Northfelt, Myra Wick, Douglas L Riegert-Johnson, Scott Okuno, Katie Kunze, Michael Golafshar, Cindy M Azevedo, PLS Uson Junior, ED Esplin, Robert Nussbaum, Margaret Klint, Sarah Mantia, Megan Hager, Keith Stewart, Niloy Jewel Samadder. Universal genetic testing in breast cancer patients: A multi-center prospective study [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 PD10-05.