Abstract PS8-30: Longitudinal clinical outcomes of a multi-center universal genetic testing registry
Authors: Beitsch Peter , Patel Rakesh , Whitworth Pat , Rosen Barry , Brown Rick , Compagnoni Gia , Gold Linsey , Grady Ian , Esplin Edward , Nielsen Sarah , Brown Max , Trudrung Melissa , Wernecke Chloe , Hardwick Mary Kay , Nussbaum Robert 
Published: February 2021

Abstract
Background: Growing evidence indicates that restrictive criteria for determining eligibility of breast cancer patients for germline genetic testing (e.g. NCCN, etc.) can missa significant number who may benefit from testing. However, the clinical utility and outcomes of patients with germline pathogenic variants (“positive patients”) who fall outside of current criteria has not been studied,and there is limited data on the clinical impact of nonBRCA pathogenic variantsin patients who fall inside testing criteria. We present longitudinal data from a previous cohort of patients, who are being followed in a new genetics registry that correlates germlinetest results with impact on clinical decision making, disease status, treatmentcourse, clinical trial enrollment and overall survival. Methods: A large multi-center IRB approved prospective Registry initiated in 2017 collected andanalyzed data on 959 breast cancer patients, newly or previously diagnosed, atthe time of genetic test result return (Beitsch et al. JCO 2018)1.This abstract presents clinical data over the intervening 18-24 months on patients with positive variants (83) both in-criteria (IC) and out-of-criteria (OOC),collected via medical record review as part of the iGAP Registry(igapregistry.org), sponsored by Medneon (Cupertino, Ca). Results: Of the 44 positive patients for whom longitudinalclinical outcomes data have been analyzed to date, 24 met guidelines fortesting and 20 did not. 6 had a history of additional primary cancers at thetime of testing. 40/44 patients are disease free; of these 20 were IC,20 were OOC. 1/44 has stable disease and was OCC. 3/44 have progressive orrecurrent breast cancer and 2 were OCC and 1 was IC. 13/44received chemotherapy; 6 IC and 7 OOC. 5 patients (with mutations in BRCA1,BRCA2, PALB2, MUTYH) received carboplatin consistent with the sensitivity toplatinum agents conferred by deficiencies in homologous recombination (HR) andbase-excision repair (BER). Longitudinal outcomes stratified by gene result arein Table 1. Conclusions:This studyprovides initial evidence for the impact of germline genetic test results onlongitudinal patient outcomes, stratified by gene. It also begins to correlategermline results and chemotherapy, as 3/5 OOC patients receiving carboplatinhad mutations in HR or BER genes. This raises the possibility that certain treatment advantages and other beneficial changes in management could bewithheld from OOC patients if restrictive criteria persist, as well as limiting the opportunities for possible preventive interventions for their at-risk family members 1. BeitschPD, Whitworth PW, Hughes K, et al. Underdiagnosis of Hereditary Breast Cancer:Are Genetic Testing Guidelines a Tool or an Obstacle?. J Clin Oncol.2019;37(6):453-460. doi:10.1200/JCO.18.01631
Table 1Positive Gene Variant# reported mutations-by geneSubject Health Status Disease FreeSubject Health Status Stable or Progressive DiseaseNCCN # ICNCCN # OOCATM22002BLM11001BRCA122020BRCA255041CHEK266033DIS3L211001FH11010MITF11010MSH611001MUTYH98127NBN22011NF110101NTLH111001PALB232121RAD5011010RAD51C22011RAD51D32112RECQL422011VHL11010
Citation Format: Peter Beitsch, Rakesh Patel, Pat Whitworth, Barry Rosen, Rick Brown, Gia Compagnoni, Linsey Gold, Ian Grady, Edward Esplin, Sarah Nielsen, Max Brown, Melissa Trudrung, Chloe Wernecke, Mary Kay Hardwick, Robert Nussbaum. Longitudinal clinical outcomes of a multi-center universal genetic testing registry [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 PS8-30.