Abstract
Neoadjuvant pembrolizumab plus chemotherapy improves outcomes in early triple-negative breast cancer, but real-world evidence in patients with pathogenic BRCA1/2 variants remains limited. We analyzed 726 consecutively treated patients from the multicenter Neo-Real/GBECAM-0123 cohort who received at least one cycle of neoadjuvant pembrolizumab plus chemotherapy and underwent surgery. Patients with pathogenic BRCA1/2 variants (mBRCA) were identified in 105 of 600 tested patients (17.5%), corresponding to 14.5% of the overall cohort. Among mBRCA carriers, 82 (78.1%) had BRCA1 variants, 22 (21.0%) had BRCA2 variants, and in 1 patient (0.1%) the BRCA subtype was not specified. The comparator group comprised 621 patients with wild-type or unknown BRCA status (wt/unknown BRCA). Pathologic complete response was higher in the mBRCA group than in the wt/unknown BRCA group (74.0% vs 61.7%). With a median follow-up of 22 months, event-free and overall survival were favorable in both groups, with a non-significant trend toward improved event-free survival in the mBRCA group, particularly among patients with residual disease.
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The authors acknowledge the contributions of all participating centers and investigators involved in data collection and study coordination. No funding was received for this research.
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The authors declare no competing non-financial interests but the following competing financial interests: R.B.S.: Speaker fees and/or honoraria for consulting or advisory functions: AstraZeneca, Daiichi-Sankyo, Eli Lilly, Gilead, Libbs, Pfizer, Novartis, MSD, and Roche. Financial support for educational programs and symposia: AstraZeneca, Daiichi-Sankyo, Gilead, Eli Lilly, and MSD. Institutional Research grant: AstraZeneca, Daiichi-Sankyo. L.L.: Speaker fees and/or honoraria for consulting or advisory functions: Adium. Travel grants: MSD, Gador. P.M.: Speaker fees and/or honoraria for consulting or advisory functions: MSD, AstraZeneca, Roche, Pfizer, Novartis, ADIUM, GSK, Gador. Institutional Research grant: Novartis, AstraZeneca, Roche, GSK. Travel grants: Astra Zeneca, Novartis, ADIUM, Roche. S.A.M.: Travel grants ADIUM, AstraZeneca, Novartis, MSD, Elea. M.R.: Travel grants: Novartis, AstraZeneca, ADIUM, Elea. M.V.C.: Speaker fees and/or honoraria for consulting or advisory functions: MSD, AstraZeneca, Roche, Pfizer, Novartis, ADIUM, Gador. Institutional Research grant: Novartis, AstraZeneca, Roche. Travel grants: Astra Zeneca, Novartis, ADIUM, Roche. J.B.: Speaker fees and/or honoraria for consulting or advisory functions: AstraZeneca, Daiichi-Sankyo, Lilly, Gilead, Pfizer, Novartis, MSD, Roche, Knight Pharmaceuticals. Financial support for educational programs and symposia: Roche, Daiichi-Sankyo. D.D.R.: Speaker fees and/or honoraria for consulting or advisory functions: AstraZeneca, Daiichi-Sankyo, Lilly, Libbs, Pfizer, Novartis, Roche, GSK, Sanofi, Amgen, Zodiac Pharma. Financial support for educational programs and symposia: Roche. D.A.S.: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo. Financial support for educational programs and symposia: AstraZeneca. J.A.P.A.: Speaker fees and/or honoraria for consulting or advisory functions: Novartis, AstraZeneca, MSD, Lilly. D.M.G.: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo, Teva, Roche, AstraZeneca, Pfizer, Lilly, Novartis. Financial support for educational programs and symposia: AstraZeneca, Libbs, Roche. Research grant: Novartis. M.S.: Speaker fees and/or honoraria for consulting or advisory functions: Adium, GSK, Travel Grants: Roche, AstraZeneca, MSD. M.R.M.: Speaker fees and/or honoraria for consulting or advisory functions: AstraZeneca, Daiichi-Sankyo, Pfizer, Novartis, Roche, MSD, Knight. Financial support for educational programs and symposia: MSD, AstraZeneca, Knight, Novartis. B.M.Z.: Speaker fees and/or honoraria for consulting or advisory functionsAstraZeneca, Daiichi-Sankyo, Eli Lilly, Gilead, Pfizer, Novartis, MSD, Roche, Addium. A.F.: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo, Novartis, Gilead, MSD, BMS, AstraZeneca, Pfizer. Financial support for educational programs and symposia: AstraZeneca, Daiichi-Sankyo, MSD, Novartis. G.C.: Speaker fees and/or honoraria for consulting or advisory functions: Amgen, AstraZeneca. Travel grants: Roche. C.H.A.: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo, Gilead AstraZeneca, Novartis, MSD. Financial support for educational programs and symposia: AstraZeneca, Daiichi-Sankyo, MSD, Lilly, Roche, Novartis, Gilead, Medscape. R.C.: Speaker fees and/or honoraria for consulting or advisory functions: AstraZeneca, Daiichi-Sankyo, Eli Lilly, Gilead, MSD, and GSK. M.M.F.M.: Speaker fees and/or honoraria for consulting or advisory functions: AstraZeneca, Daiichi-Sankyo, Eli Lilly, Gilead, Addium, Novartis, MSD, and Roche. Financial support for educational programs and symposia: AstraZeneca, Daiichi-Sankyo, Gilead, Eli Lilly, Roche, MSD and Novartis. P.M.H.: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo. L.T.: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo, MSD, AstraZeneca, Pfizer, Lilly, Novartis. Financial support for educational programs and symposia: AstraZeneca, Roche, Gilead. Institutional Research grant: Novartis. C.P.: Speaker fees and/or honoraria for consulting or advisory functions: Knight. Travel grants: Astra Zeneca, Gador, Novartis, Pfizer, Raffo, Roche. R.C.B.: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo, Nestle Health Science, Addium, Gilead, MSD, BMS, AstraZeneca, Ache, Pfizer, Roche, Libbs, Lilly, Novartis, and GSK. Financial support for educational programs and symposia: AstraZeneca, Daiichi-Sankyo, MSD. Institutional Research grant: Novartis, AstraZeneca. I.M.S., F.C.B., M.C.T., F.M., R.P.F., G.R., C.L.S., and Z.S.S. declare no conflict of interest.
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Tavares, M.C., Balint, F.C., Barroso-Sousa, R. et al. Neoadjuvant pembrolizumab plus chemotherapy in germline BRCA-mutated early triple-negative breast cancer: a multicenter real-world cohort. npj Breast Cancer (2026). https://doi.org/10.1038/s41523-026-00966-5
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DOI: https://doi.org/10.1038/s41523-026-00966-5
