Clinical Behavior of Breast Cancer in Young BRCA Carriers and Prediagnostic Awareness of Germline BRCA Status
- Author(s)
- Lambertini, M; Blondeaux, E; Tomasello, LM; Agostinetto, E; Hamy, AS; Kim, HJ; Franzoi, MA; Bernstein-Molho, R; Hilbers, F; Pogoda, K; Wildiers, H; Bajpai, J; Ignatiadis, M; Moore, HCF; Partridge, AH; Phillips, KA; Toss, A; Rousset-Jablonski, C; Criscitiello, C; Renaud, T; Ferrari, A; Paluch-Shimon, S; Fruscio, R; Cui, W; Wong, SM; Vernieri, C; Ruddy, KJ; Dieci, MV; Matikas, A; Rozenblit, M; Villarreal-Garza, C; De Marchis, L; Puglisi, F; Rodriguez-Wallberg, KA; Duhoux, FP; Livraghi, L; Bruzzone, M; Boni, L; Balmaña, J;
- Journal Title
- Journal of Clinical Oncology
- Publication Type
- Online publication before print
- Abstract
- PURPOSE: 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. METHODS: This 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). RESULTS: 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% 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]). CONCLUSION: 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.
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1200/jco-24-01334
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- Refer to copyright notice on published article.
Creation Date: 2025-03-21 02:49:46
Last Modified: 2025-03-21 02:54:49