Matteo Lambertini , Eva Blondeaux , Loredana M Tomasello.et al. J Clin Oncol. 2025 May 10;43(14):1706-1719
To investigate the clinical behavior of breast cancer in young BRCA carriers according to the specific BRCA gene (BRCA1 v BRCA2) and the association of the timing of genetic testing (before v at diagnosis) with prognosis. Compared with BRCA2 carriers (n = 1,683), BRCA1 carriers (n = 3,069) had more frequently hormone receptor-negative (74.4% v 15.5%) and high-grade (77.5% v 49.1%) tumors. Similar outcomes were observed in BRCA1 and BRCA2 carriers but with a different pattern and risk of disease-free survival events over time. Compared with patients tested for BRCA at diagnosis (ie, between 2 months before and up to 6 months after diagnosis; n = 1,671), those tested before diagnosis (ie, any time up to 2 months before diagnosis; n = 411) had smaller tumors (T1: 61.3% v32.4%), less nodal involvement (N0: 65.9% v 50.8%), less frequently received chemotherapy (84.4% v 92.9%), and axillary dissection (37.5% v 47.4%). Patients tested before diagnosis had better overall survival (OS; unadjusted hazard ratio [HR], 0.61 [95% CI, 0.40 to 0.92]); however, this result lost statistical significance after adjustment for potential confounders including tumor stage (adjusted HR, 0.74 [95% CI, 0.47 to 1.15]). This global study provides evidence on the different clinical behavior of breast cancer in young BRCA1 and BRCA2 carriers. Identifying a BRCA PV in healthy individuals was associated with earlier-stage breast cancer diagnosis and lower treatment burden, as well as better unadjusted OS.
24 Mar, 2026