Pathologic complete response after neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers Journal Article
| Authors: | Myers, S. P.; Sevilimedu, V.; Barrio, A. V.; Tadros, A. B.; Mamtani, A.; Robson, M. E.; Morrow, M.; Lee, M. K. |
| Article Title: | Pathologic complete response after neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers |
| Abstract: | BRCA1 and BRCA2 pathogenic variant carriers develop breast cancers with distinct pathological characteristics and mutational signatures that may result in differential response to chemotherapy. We compared rates of pathologic complete response (pCR) after NAC between BRCA1/2 variant carriers and noncarriers in a cohort of 1426 women (92 [6.5%] BRCA1 and 73 [5.1%] BRCA2) with clinical stage I–III breast cancer treated with NAC followed by surgery from 11/2013 to 01/2022 at Memorial Sloan Kettering Cancer Center. The majority received doxorubicin/cyclophosphamide/paclitaxel therapy (93%); BRCA1/2 carriers were more likely to receive carboplatin (p < 0.001). Overall, pCR was achieved in 42% of BRCA1 carriers, 21% of BRCA2 carriers, and 26% of noncarriers (p = 0.001). Among clinically node-positive (cN+) patients, nodal pCR was more frequent in BRCA1/2 carriers compared to noncarriers (53/96 [55%] vs. 371/856 [43%], p = 0.015). This difference was seen in HR+/HER2− (36% vs. 20% of noncarriers; p = 0.027) and TN subtypes (79% vs. 45% of noncarriers; p < 0.001). In a multivariable analysis of the overall cohort, BRCA1 status, and TN and HER2+ subtypes were independently associated with pCR. These data indicate that BRCA1 carriers may be more likely to achieve overall and nodal pCR in response to NAC compared with BRCA2 carriers and patients with sporadic disease. Further studies with a larger cohort of BRCA1/2 mutation carriers are needed, as a small sample size may have a restricted ability to detect a significant association between mutational status and pCR in sensitivity analyses stratified by subtype and adjusted for clinically relevant factors. © The Author(s) 2024. |
| Keywords: | immunohistochemistry; adult; cancer chemotherapy; human tissue; gene mutation; major clinical study; overall survival; clinical feature; doxorubicin; paclitaxel; neoadjuvant therapy; cancer staging; sensitivity analysis; carboplatin; breast cancer; mastectomy; epidermal growth factor receptor 2; cohort analysis; cyclophosphamide; brca1 protein; brca2 protein; heterozygote; histology; fluorescence in situ hybridization; partial mastectomy; multivariate analysis; estrogen receptor; progesterone receptor; race; axillary lymph node dissection; pathological complete response; triple negative breast cancer; lymph vessel metastasis; human epidermal growth factor receptor 2 positive breast cancer; human; female; article; ductal breast carcinoma in situ; invasive lobular breast carcinoma; sporadic disease |
| Journal Title: | npj Breast Cancer |
| Volume: | 10 |
| ISSN: | 2374-4677 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-07-26 |
| Start Page: | 63 |
| Language: | English |
| DOI: | 10.1038/s41523-024-00674-y |
| PROVIDER: | scopus |
| PMCID: | PMC11282097 |
| PUBMED: | 39060255 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Minna K. Lee -- Source: Scopus |
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