BRCA1 and 2 Mutations and Efficacy of Pembrolizumab-Based Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer: A Real-World Multicenter Analysis
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Le résumé fourni par la source
Background: Pembrolizumab has reshaped the neoadjuvant treatment landscape for triple-negative breast cancer (TNBC). However, the influence of BRCA1/2 mutational status on the efficacy of chemo-immunotherapy remains unclear, particularly in real-world settings. Since BRCA-mutated tumors exhibit homologous recombination deficiency (HRD) and high genomic instability, they may be more immunogenic and responsive to immune checkpoint inhibitors. This multicenter study investigated the association between BRCA1/2 mutations and pathologic complete response (pCR) in TNBC patients treated with pembrolizumab-based neoadjuvant chemotherapy (NACT). Methods: We retrospectively analyzed 184 patients with stage II–III TNBC treated between 2021 and 2024 across eleven Italian oncology centers. All received pembrolizumab combined with platinum- and taxane-based NACT followed by anthracyclines, according to the KEYNOTE-522 regimen. Germline BRCA1/2 status was determined by next-generation sequencing. The primary endpoint was pCR, defined as ypT0/is ypN0. Fisher’s exact test and logistic regression models were used to assess associations between clinical–pathological variables and pCR. Results: Among 184 patients, 25 (13.6%) harbored BRCA1 mutations, 12 (6.5%) BRCA2 mutations, and 147 (79.9%) were wild-type. pCR was achieved in 80.0% of BRCA1-mutated, 75.0% of BRCA2-mutated, and 61.1% of wild-type tumors. When pooled, BRCA1/2-mutated cases showed a higher likelihood of achieving pCR (78.4% vs. 61.1%; odds ratio [OR] = 2.17; 95% CI 1.01–4.97; p = 0.056). High tumor-infiltrating lymphocytes (≥30%) were also associated with increased pCR rates. The frequency of BRCA mutations (20.1%) was consistent with that reported in major TNBC series. No comparative analysis of toxicity or survival outcomes was performed due to the retrospective design and limited follow-up. Conclusions: In this multicenter real-world cohort, TNBC patients carrying BRCA1/2 mutations exhibited a trend toward higher pCR rates with pembrolizumab-based NACT compared with wild-type tumors. These findings suggest enhanced chemosensitivity and immune responsiveness in BRCA-deficient disease, warranting further validation in larger prospective studies with survival endpoints.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- BRCA1 and 2 Mutations and Efficacy of Pembrolizumab-Based Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer: A Real-World Multicenter Analysis
- Date Crossref
- 14/12/2025
- Éditeur
- MDPI AG
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Istituto Tumori Bari pays non établi dans la noticeÉtablissement de santé
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University of Foggia Department of Medical and Surgical Sciences pays non établi dans la noticeUniversité ou école supérieure
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Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari pays non établi dans la noticeÉtablissement de santé
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University of Bari Aldo Moro pays non établi dans la noticeUniversité ou école supérieure
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Casa Sollievo della Sofferenza pays non établi dans la noticeÉtablissement de santé
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Ospedale San Paolo pays non établi dans la noticeÉtablissement de santé
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Centro di Riferimento Oncologico della Basilicata pays non établi dans la noticeÉtablissement de santé
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Ospedale San Carlo pays non établi dans la noticeÉtablissement de santé
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Ospedale Sacro Cuore Don Calabria pays non établi dans la noticeÉtablissement de santé
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Dario Camberlingo Hospital Oncology Unit pays non établi dans la noticeÉtablissement de santé
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S.S.D. C.O.r.O. Bed Management Presa in Carico pays non établi dans la noticeInstitution
Istituto Tumori Bari, Department of Medical and Surgical Sciences — University of Foggia et Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.