Abstract P1-09-02: Prevalence of genetic mutations in patients with second primary breast cancers

Background: Women newly diagnosed with primary breast cancer (PBC) often undergo multi-gene panel testing to determine their contralateral breast cancer (BC) risk and whether a contralateral prophylactic mastectomy is warranted. However, with the exception of BRCA1/2, gene-specific associations with contralateral or second PBC (SPBC) have not been established. Methods: The study sample was comprised of 83,278 women with BC referred to a single diagnostic laboratory for multi-gene panel testing. The frequency of pathogenic/likely pathogenic variants in clinically-actionable genes (CAG), including highly penetrant genes (HPG: BRCA1, BRCA2, TP53, PTEN) and moderately penetrant genes (MPG: ATM, CHEK2, PALB2, CDH1, NBN, NF1) was compared between women with a PBC and SPBC. Women with a SPBC 1 first or second degree relative with BC (62.2% vs. 60.8%; p=0.004) than PBC. Among women tested for all CAGs, 4,883 (8.1%) were carriers of pathogenic/likely pathogenic variants (11.1% SPBC vs. 7.8% PBC). CHEK2 was the most frequently mutated gene (3.4% SPBC vs. 2.3% PBC), followed by BRCA1 (2.7% SPBC vs.1.6% PBC), BRCA2 (2.2% SPBC vs. 1.8% PBC), and PALB2 (1.4% SPBC vs. 0.9% PBC). In fully adjusted models, women with SPBC were 1.38 times as likely (p= Citation Format: Yao K, Clifford J, Li S, LaDuca H, Hulick PJ, Xu J, Gutierrez S, Black MH. Prevalence of genetic mutations in patients with second primary breast cancers [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-09-02.