Impact of Germline BRCA Status on Pathologic Complete Response (pCR) and Outcomes in Early TNBC Treated with Pembrolizumab-Based Neoadjuvant Chemotherapy (KEYNOTE-522 Regimen): A Real-World Study.

Authors

Mohammad Aldawoud, Fatima Faqihi, Najd Algazlan, Marwa Alharbi, Abdullah Almazyad, Abdulaziz Altamimi, Mojahed Rudaini, Abdullah Alwohaibi, Besher Alghazi, Abdulrahman Alturki, Hatoon Bakhribah, Abdullah Altwairgi

Published in

Journal of immunotherapy and precision oncology. Volume 9. Issue 3. Pages 113-119. Epub Jul 17, 2026.

Abstract

Pembrolizumab-based neoadjuvant chemoimmunotherapy following the KEYNOTE-522 regimen (NCT03036488) is a standard treatment approach for stage II and III triple-negative breast cancer (TNBC). Real-world evidence on the impact of germline BRCA status on pathologic complete response (pCR) and survival outcomes remains limited.
We performed a retrospective single-center cohort study of patients with stage II-III TNBC treated with a KEYNOTE-522 regimen between January 2021 and December 2023. Only patients with documented germline BRCA status were included. The primary end point was pCR rate, defined as achievement of ypT0/is ypN0. Secondary end points included treatment delivery (completion and early discontinuation), postneoadjuvant systemic therapy patterns, recurrence-free survival (RFS), and overall survival (OS). Categorical variables were compared using Fisher's exact test, and survival outcomes were estimated using Kaplan-Meier methods and compared with log-rank tests.
Among 1004 patients with breast cancer screened between 2021 and 2023, 125 had TNBC. After exclusion of patients who did not receive a KEYNOTE-522 regimen, had metastatic disease, underwent definitive surgery before neoadjuvant systemic therapy, had unretrievable BRCA status, or had other missing key eligibility data, 54 patients were eligible for analysis. The final cohort included 11 patients who were BRCA+ and 43 who were BRCA-. The BRCA+ patients were younger than BRCA- patients (median 38 vs 46 years; p = 0.018). pCR was evaluable in 52 patients and was achieved in 31 of 52 patients (60%) overall; pCR was numerically higher in BRCA+ vs BRCA- patients (73% [8 of 11] vs 56% [23 of 41]; p = 0.49). Median follow-up was 25 months. Two-year RFS was 100% in BRCA+ and 75.4% in BRCA- patients (log-rank p = 0.068), whereas 2-year OS was 100% and 88%, respectively (log-rank p = 0.272). Within the BRCA+ subgroup, the prognostic significance of pCR could not be assessed because no recurrence or death events were observed during follow-up. Within the BRCA- subgroup, pCR strongly stratified prognosis, with 2-year RFS of 100% in patients achieving pCR vs 45.5% in those without pCR (log-rank p = 0.00004), and 2-year OS of 100% vs 72.7%, respectively (log-rank p = 0.018).
Germline BRCA positivity was associated with a numerically higher pCR rate, but differences in pCR and survival by BRCA status were not statistically significant. Given the limited sample size and low event counts, these findings should be considered hypothesis-generating. Recurrence events clustered in BRCA- patients and were driven predominantly by those without pCR, supporting further study of optimized postneoadjuvant escalation strategies for residual BRCA- disease.

PMID:
42517077
Bibliographic data and abstract were imported from PubMed on 28 Jul 2026.

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