Abstract 6484: Impact of time between last childbirth and diagnosis of early-onset breast cancer on survival in germline BRCA1/2 carriers

Abstract

Abstract INTRODUCTION: Young women diagnosed with breast cancer in close proximity to childbirth have increased risk of mortality compared to nulliparous women, and the postpartum period has been identified as a risk window for breast cancer metastasis. BRCA1/2 germline mutation carriers have a high risk of developing breast cancer at young age, yet it is unknown if recent childbirth is a poor prognostic risk factor for BRCA1/2 carriers. Here we assessed whether time between last childbirth and breast cancer diagnosis impacted survival among early-onset BRCA1/2 breast cancer patients. METHODS: The study population includes 903 female BRCA1/2 mutation carriers diagnosed with stage I-III breast cancer at ≤45 years of age between 1950 and 2021 in the UK. The primary outcome of this study is all-cause mortality. The primary exposures were no prior childbirth (n=224), or time between last childbirth and breast cancer diagnosis grouped as 0-<5 years (n=228), 5-<10 years (n=191), or ≥10 years since last childbirth (n=260). Cox proportional hazards regression was applied to identify factors associated with risk of 20-year mortality. RESULTS: Breast cancer diagnosed 5-<10 years after last childbirth was associated with an elevated risk for mortality [HR=1.56 (95% CI, 1.05-2.30)] compared to nulliparous cases after adjusting for patient age and tumor stage. Across groups, nulliparous women had the best prognosis, suggesting parity may increase risk of death in BRCA1/2 carriers. ER-negative cancers were the dominant tumor type across all groups: 54.8% (nulliparous), 52.6% [postpartum breast cancer (PPBC) <5], 58.4% (PPBC 5-<10), and 54.0% (≥10). ER-negative cases were more prevalent among BRCA1 carriers (77%) compared to BRCA2 carriers (24%). In stratified analyses by either ER or BRCA status, increased mortality in the PPBC 5-<10 group was significant for ER-negative cases [HR=3.12 (95% CI, 1.22-7.97)] and BRCA1 carriers [HR=2.03 (95% CI, 1.15-3.58)], compared to nulliparous groups. For ER-positive cases, 71% of cases were BRCA2 carriers, and the most significant postpartum interval among ER-positive cases was observed in the 0-<5 group [HR=2.35 (95% CI, 1.02-5.42)]. No association was observed for BRCA2 carriers with PPBC 0-<5 vs nulliparous groups [HR=1.26 (95% CI, 0.73-2.16)].CONCLUSION: Results suggest that BRCA1/2 breast cancer patients are at increased risk for all-cause mortality if diagnosed within 10 years of childbirth. For ER-positive disease, poorest prognosis occurs within 0-5 years postpartum, consistent with promotion of existing sub-clinical tumors. For BRCA2 carriers, the association between postpartum diagnosis and mortality is weak. For ER-negative disease, similar to BRCA1 carriers, poorest prognosis occurs 5-10 years postpartum, suggesting an interaction between BRCA1 and parity may result in increased tumor initiation. Citation Format: Zhenzhen Zhang, Shangyuan Ye, D Gareth Evans, Pepper Schedin. Impact of time between last childbirth and diagnosis of early-onset breast cancer on survival in germline BRCA1/2 carriers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6484.