Surgical Management of Early-Onset Breast Cancer Among Young BRCA1 and BRCA2 Carriers.

Choice of initial surgical procedure for stage I to III invasive breast cancer in women aged 40 years or younger carrying a germline pathogenic variant in BRCA1 or BRCA2.

The BRCA BCY Collaboration (Breast Cancer in Young patients, a cohort of BRCA1/BRCA2 carriers aged 40 years or younger) is an international hospital-based retrospective cohort study across 109 centres on 5 continents, including women diagnosed between 2000 and 2020 with stage I to III invasive breast cancer. Among 4,715 carriers analysed (median age 35 years, IQR 31-38), 1,805 (38.3%) underwent breast-conserving surgery, 1,752 (37.2%) unilateral mastectomy and 1,158 (24.6%) bilateral mastectomy. Breast-conserving surgery fell from 55.7% in 2000 to 27.0% in 2020, while bilateral mastectomy rose from 8.0% to 44.4%. On multivariable analysis, the factor most strongly associated with bilateral mastectomy was genetic testing performed before diagnosis (adjusted odds ratio 20.72; 95% CI 15.27-28.13) or at diagnosis (6.83; 5.39-8.66). Among the 2,327 women tested before or within 6 months of diagnosis, bilateral mastectomy rates ranged from 26.1% in Asia and Africa to 66.4% in North America.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

It is not biology that determines the extent of surgery, but the date the genetic result arrives and the country where the operation takes place. An adjusted odds ratio of 20.7 for testing before diagnosis alone shows that care-pathway organisation weighs more heavily than any estimate of contralateral risk. The operational consequence is straightforward: if surgical decisions are to be genuinely informed, testing must precede rather than follow the scheduling of surgery.

Analysis by Dr Thibaut Benquey