| Contributors: |
Lambertini, M.; Blondeaux, E.; Tomasello, L. M.; Agostinetto, E.; Hamy, A. S.; Kim, H. J.; Franzoi, M. A.; Bernstein-Molho, R.; Hilbers, F.; Pogoda, K.; Wildiers, H.; Bajpai, J.; Ignatiadis, M.; Moore, H. C. F.; Partridge, A. H.; Phillips, K. A.; Toss, A.; Rousset-Jablonski, C.; Criscitiello, C.; Renaud, T.; Ferrari, A.; Paluch-Shimon, S.; Fruscio, R.; Cui, W.; Wong, S. M.; Vernieri, C.; Ruddy, K. J.; Dieci, M. V.; Matikas, A.; Rozenblit, M.; Villarreal-Garza, C.; De Marchis, L.; Puglisi, F.; Rodriguez-Wallberg, K. A.; Duhoux, F. P.; Livraghi, L.; Bruzzone, M.; Boni, L.; Balmaña, J. |
| Description: |
PURPOSETo 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.METHODSThis was an international, multicenter, hospital-based, retrospective cohort study that included 4,752 patients harboring germline pathogenic/likely pathogenic variants (PVs) in BRCA1 or BRCA2, who were diagnosed with stage I-III invasive breast cancer at 40 years or younger between January 2000 and December 2020 in 78 centers worldwide (ClinicalTrials.gov identifier: NCT03673306).RESULTSCompared 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% v 32.4%), 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]).CONCLUSIONThis 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. |