Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: an international cohort study

Blondeaux et al. Lancet Oncol. 2025 Jun;26(6):759-770. doi: 10.1016/S1470-2045(25)00152-4. Epub 2025 May 8. PMID: 40347973

This international retrospective cohort study, conducted across 109 centres in 20 countries, examined the survival impact of risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) in BRCA1/2 carriers diagnosed with Stage I–III breast cancer aged 40 or younger. It is the largest study to address this question specifically in carriers with a prior breast cancer diagnosis, distinguishing it meaningfully from the prevention literature in unaffected carriers.

Of 5,290 women analysed (63.5% BRCA1; 35.7% BRCA2), 55% underwent RRM, 53% underwent RRSO, and 34% underwent both, over a median follow-up of 8 years. RRM was associated with a 35% lower risk of death (aHR 0.65), consistent across BRCA1 and BRCA2 carriers regardless of tumour subtype or stage. RRSO was associated with a 42% lower risk of death overall (aHR 0.58), though the benefit was substantially greater in BRCA1 carriers (aHR 0.44) than BRCA2 carriers (aHR 0.86, not statistically significant) - a clinically important distinction for genotype-specific counselling.

Significant methodological caveats apply. The retrospective design introduces healthy-user bias, immortal-time bias, and incomplete surgical timing data. Applicability is further limited by advances in systemic therapy and evolving guidelines - including earlier RRSO recommendations for BRCA1 carriers - that postdate much of the study period.

Nonetheless, these findings add meaningful, evidence-based weight to shared decision-making conversations balancing survival benefit against fertility, menopause, and quality-of-life considerations.

Summary author: Ms Anna Isaac, Senior Registrar in Oncoplastic Surgery, Belfast City Hospital