Safety of having a subsequent pregnancy after prior diagnosis of breast cancer during pregnancy in young BRCA carriers

Abstract

Background For women carrying a germline pathogenic or likely pathogenic variant in the BRCA1/2 genes, having a pregnancy following breast cancer diagnosis and treatment is safe. However, no evidence exists on the safety of having a subsequent pregnancy in BRCA carriers with a prior diagnosis of breast cancer during pregnancy (PrBC). Methods The BRCA BCY Collaboration (NCT03673306) is an international, multicenter, retrospective cohort study that included BRCA carriers diagnosed with invasive breast cancer at the age ≤40 years between January 2000 and December 2020. This analysis included only women diagnosed with PrBC comparing patients who had a subsequent pregnancy to those without. Primary endpoints were the cumulative incidence of having a subsequent pregnancy and disease-free survival (DFS). Secondary endpoints were overall survival, pattern of first DFS events and reproductive outcomes. Results Of 6238 BRCA carriers from 109 centers worldwide, 282 patients with PrBC were included in this analysis, of whom 68 had a subsequent pregnancy and 214 did not. The 10-year cumulative incidence of having a subsequent pregnancy was 36.6% [95% confidence interval (CI) 29.5% to 44.8%]. Patients with a subsequent pregnancy were more likely to be younger at diagnosis (median age 31 years versus 34 years) and to have triple-negative tumors (73.5% versus 55.1%). Among patients with a subsequent pregnancy, median time from diagnosis to conception was 3.3 years (interquartile range 2.0-4.3 years). Most pregnancies were delivered at term (≥37 weeks, 75.9%) and without complications (74.1%). Median follow-up was 7.3 years (interquartile range 4.5-11.9 years). No differences in DFS (adjusted hazard ratio (HR) 1.06, 95% CI 0.49-2.31) nor overall survival (adjusted HR 0.63, 95% CI 0.19-2.05) were observed between patients with or without a subsequent pregnancy. Conclusions In this global study, one out of three young BRCA carriers diagnosed with PrBC had a subsequent pregnancy. No concerning signals in terms of maternal prognosis or reproductive outcomes were observed.