Genetics and family history in a diverse cohort of females with early-onset breast cancer.

Abstract

10613 Background: Genetic testing for breast cancer susceptibility genes is a crucial component of clinical care for patients with early-onset breast cancer (EOBC) diagnosed < age 50 with implications for treatment and surgical decision-making, future surveillance, and cascade genetic testing for family. Limited data exist regarding prevalence of pathogenic/likely pathogenic variants (P/LPV) and patterns of family history (FH) of cancer across diverse patient populations and merit further research given the rise in EOBC rates. This study examines a cohort of EOBC patients from a cancer genetics program at a comprehensive cancer center to derive insights into the genetic and FH spectrum for a diverse cohort of patients with EOBC in hopes of informing clinical care and public awareness strategies. Methods: A retrospective analysis of women seen in the Smilow Cancer Genetics and Prevention program at Yale-New Haven Hospital from 2015-2023 was conducted. Women diagnosed with EOBC who underwent germline genetic testing were included. Data on demographics, age at diagnosis, genetic test results, and FH of breast, ovarian, pancreatic, and prostate cancer in 1 st /2 nd /3 rd degree relatives was obtained from the electronic medical record and Progeny family history software using manual and automated querying and natural language processing. The dataset was assessed for frequency of P/LPVs in cancer predisposition genes, variants of uncertain significance (VUS), and FH of cancer. Fisher’s exact test was used to assess the association between categorical variables, and ANOVA to assess the difference in continuous variables among groups. Results: 1676 women with available race and ethnicity data were analyzed. Patients identified as White (83.3%), Black (11.5%), Asian (5.3%). 5% of all patients identified as Latinx. Mean age at diagnosis was 42.4 years (SD 5.48 years). P/LPVs were identified in 15.1% and VUS in 22.6%. The most common genes with P/LPVs were ATM (4.8%), BRCA2 (4.1%), CHEK2 (4.1%), and BRCA1 (3.0%). Rates of Ashkenazi Jewish ancestry were higher for Whites (7.5%) compared to Blacks (1.0%) and Asians (1.0%) (p<0.001). Family history of breast cancer was higher among Black (80.2%) and White patients (80.9%) than Asians (53.4%) (p<0.001), as was history of prostate cancer (Black, 29.7%; White, 29%; Asian, 11.4%, p=0.017). P/LPV rates were highest among Whites (15.8%), followed by Blacks (11.5%) and Asians (10.2%) while VUS rates were highest for Asians (34.1%) and Blacks (28.6%) than Whites (21.0%) (p<0.001). Conclusions: Our results from a diverse EOBC population underscore the higher rates of P/LPVs among White patients while non-White populations have higher rates of VUS. Given the rise in EOBC rates, greater genetic insights as well as additional factors impacting EOBC risk need to be identified and studied particularly across diverse racial/ethnic populations.