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.

Key words: breast cancer, BRCA, pregnancy, oncofertility, survivorship