Abstract C008: Characterizing factors associated with early onset breast cancer to inform tailored strategies for cancer risk assessment, screening, and treatment

Abstract Background Early onset breast cancer (EOBC) diagnosed before age 50 is on the rise; there is a need to characterize associated factors to inform appropriate screening, risk reduction, and treatment. This retrospective study compared clinical, pathologic, family history (FH), and genetic factors between EOBC cohort (≤ 49 years) and late-onset breast cancer (LOBC, diagnosed ≥ 50 years) from a tertiary care cancer genetics and prevention program to gain insights into EOBC and inform strategies to reduce the burden of this disease. Methods We conducted a retrospective study of 4, 461 female breast cancer patients seen from 2015–2023 at the Yale/Smilow Cancer Genetics 0. 0001). EOBC patients had higher rates of BRCA1 (2. 1% vs. 1. 2%, p=0. 0203) and BRCA2 mutations (pathogenic variants) (2. 9% vs. 1. 3%, p=0. 0001), lower proportion of hormone receptor positive / HER2 negative tumors (36. 7% vs. 46. 4%, p 0. 0001), and higher rate of triple positive subtype (3. 4% vs. 2. 3%, p=0. 0366). Family history of breast cancer was less frequent in EOBC (80. 0% vs. 96. 9%, p 0. 0001), though FH of ovarian, pancreatic, and prostate cancers were all higher in the EOBC cohort (p-values 0. 0267, 0. 0387, 0. 0021 respectively). In a subset analysis (n=444), family history of breast cancer was associated with aggressive disease (N0, T3/T4 disease) for patients with LOBC vs. EOBC (100% vs. 88. 57%, p0. 0001). Conclusions Patients with EOBC may have a more notable family history for cancers beyond breast cancer, compared to the patients with LOBC. This finding deserves confirmation and may inform strategies to increase awareness of broad family history assessment, screening, and genetic testing. High penetrance gene mutations, particularly in BRCA1 and BRCA2, are more common in patients with EOBC as are more aggressive receptor subtypes of disease, which is consistent with current state of the field. These findings reinforce the need for tailored risk stratification, genetic counseling, and prevention strategies focused on younger women, especially to improve early detection and equity in outcomes. Further research is needed to uncover additional factors related to EOBC predisposition and aggressive biology to optimize clinical outcomes. Citation Format: Guannan Gong, Tanaya Shroff, Wei Cheng, Aparna Namboodiri, Laura Gross, Nancy A. Borstelmann, Veda N. Giri, Ellie Proussaloglou. Characterizing factors associated with early onset breast cancer to inform tailored strategies for cancer risk assessment, screening, and treatment abstract. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31 (23Suppl): Abstract nr C008.