Clinical Behavior of Breast Cancer in Young Carriers and Prediagnostic Awareness of Germline Status.
(2025) Journal of clinical oncology : official journal of the American Society of Clinical Oncology — Vol. 2025, n° 2025, p. JCO2401334 (2025)
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- Authors
Lambertini, Matteo 
Blondeaux, Eva Agostinetto, Elisa Balmaña, Judith
- Abstract
- To investigate the clinical behavior of breast cancer in young carriers according to the specific gene () and the association of the timing of genetic testing (before at diagnosis) with prognosis. This was an international, multicenter, hospital-based, retrospective cohort study that included 4,752 patients harboring germline pathogenic/likely pathogenic variants (PVs) in or , 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). Compared with carriers (n = 1,683), carriers (n = 3,069) had more frequently hormone receptor-negative (74.4% 15.5%) and high-grade (77.5% 49.1%) tumors. Similar outcomes were observed in and carriers but with a different pattern and risk of disease-free survival events over time. Compared with patients tested for 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% 32.4%), less nodal involvement (N0: 65.9% 50.8%), less frequently received chemotherapy (84.4% 92.9%), and axillary dissection (37.5% 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 and carriers. Identifying a PV in healthy individuals was associated with earlier-stage breast cancer diagnosis and lower treatment burden, as well as better unadjusted OS.
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Citations
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., et al. (2025). Clinical Behavior of Breast Cancer in Young Carriers and Prediagnostic Awareness of Germline Status. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2025(2025), JCO2401334. https://doi.org/10.1200/JCO-24-01334 (Original work published 2025)