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 5 1,683), BRCA1 carriers (n 5 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 5 1,671), those tested before diagnosis (ie, any time up to 2 months before diagnosis; n 5 411) 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.
Clinical Behavior of Breast Cancer in Young BRCA Carriers and Prediagnostic Awareness of Germline BRCA Status / Lambertini, Matteo; Blondeaux, Eva; Tomasello, Loredana M.; Agostinetto, Elisa; Hamy, Anne-Sophie; Kim, Hee Jeong; Franzoi, Maria Alice; Bernstein-Molho, Rinat; Hilbers, Florentine; Pogoda, Katarzyna; Wildiers, Hans; Bajpai, Jyoti; Ignatiadis, Michail; Moore, Halle C. F.; Partridge, Ann H.; Phillips, Kelly-Anne; Toss, Angela; Rousset-Jablonski, Christine; Criscitiello, Carmen; Renaud, Tiphaine; Ferrari, Alberta; Paluch-Shimon, Shani; 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.; Duhoux, Francois P.; Livraghi, Luca; Bruzzone, Marco; Boni, Luca; Balmaña, Judith. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - 43:14(2025), pp. 1706-1719. [10.1200/jco-24-01334]
Clinical Behavior of Breast Cancer in Young BRCA Carriers and Prediagnostic Awareness of Germline BRCA Status
De Marchis, Laura;
2025
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 5 1,683), BRCA1 carriers (n 5 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 5 1,671), those tested before diagnosis (ie, any time up to 2 months before diagnosis; n 5 411) 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.| File | Dimensione | Formato | |
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