Citations 1
Clinical Behavior of Breast Cancer in Young BRCA Carriers and Prediagnostic Awareness of Germline BRCA Status
Lambertini, Matteo , Blondeaux, Eva , Tomasello, Loredana Maria, Agostinetto, Elisa , Hamy, Anne‐Sophie , Kim, Hee Jeong , Franzoi, Maria Alice , Bernstein‐Molho, Rinat , Hilbers, Florentine , Pogoda, Katarzyna , Bajpai, Jyoti , Phillips, Kelly‐Anne , Rousset‐Jablonski, Christine , Renaud, Tiphaine , Cui, Wanyuan , Wong, Stephanie M. , Ruddy, Kathryn J. , Marchis, Laura De , Wildiers, Hans , Bajpai, Jyoti , Ignatiadis, Michail , Moore, Halle C F , Partridge, Ann H , Phillips, Kelly-Anne , Toss, Angela , Rousset-Jablonski, Christine , Criscitiello, Carmen , Ferrari, Alberta , Fruscio, Robert , Cui, Wanda , Wong, Stephanie M , Vernieri, Claudio , Ruddy, Kathryn J , Dieci, Maria Vittoria , Matikas, Alexios , Rozenblit, Mariya , Villarreal-Garza, Cynthia , De Marchis, Laura , Puglisi, Fabio , Rodriguez-Wallberg, Kenny A , Livraghi, Luca , Bruzzone, Marco , Boni, Luca , Balmaña, Judith , Lambertini, Matteo , Hamy, Anne-Sophie , Pogoda, K. , Wildiers, Hans , Ignatiadis, Michail , Moore, Halle C. F. , Partridge, Ann H. , Paluch–Shimon, Shani , Fruscio, Robert , Dieci, Maria Vittoria , Villarreal‐Garza, Cynthia , Duhoux, François P. , Livraghi, Luca , Bruzzone, Marco , Balmañà, Judith
Journal of Clinical Oncology | February 24, 2025 | Volume: 43 | Issue: 14 | Pages: 1706-1719
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.