Mutational status is associated with a higher rate of pathologic complete response after neoadjuvant chemotherapy in hormone receptor-positive breast cancer 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: | Mutational status is associated with a higher rate of pathologic complete response after neoadjuvant chemotherapy in hormone receptor-positive breast cancer |
| Abstract: | Background: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) occurs in up to 20% of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancers. Whether this differs among BRCA mutation carriers is uncertain. This study compared pCR between BRCA1/2 mutation carriers and matched sporadic control subjects. Methods: From November 2013 to January 2022, this study identified 522 consecutive women with clinical stage I to III HR+/HER2− breast cancer treated with NAC and surgery. The study matched BRCA1/2 mutation carriers 1:2 to non-carriers in terms of age, clinical tumor (cT) and nodal (cN) stage, and differentiation. Two-sample non-parametric tests compared baseline characteristics. Multivariable logistic regression assessed pCR (i.e., ypT0/ispN0) by BRCA1/2 mutational status. Results: Of the 522 women (median age, 50 years), 59 had BRCA1/2 mutations, 78% of which were clinically node positive. Anthracycline-based NAC was administered to 97%. More BRCA1/2 mutation carriers were younger, had cT1 tumors, and had poorly differentiated disease. After matching, 58 BRCA1/2 mutation carriers were similar to 116 non-carriers in terms of age (p = 0.6), cT (p = 0.9), cN stage (p = 0.7), and tumor differentiation (p > 0.9). Among the mutation carriers, the pCR rate was 15.5% for BRCA1/2, 38% (8/21) for BRCA1, and 2.7% (1/37) for BRCA2 versus 7.8% (9/116) for the non-carriers (p < 0.001). After NAC, 5 (41.7%) of the 12 BRCA1 mutation carriers converted to pN0 versus 10 (37%) of the 27 BRCA2 mutation carriers and 19 (20.9%) of the 91 non-carriers (p = 0.3). In the multivariable analysis, BRCA1 mutation status was associated with higher odds of pCR than non-carrier status (odds ratio [OR] 6.31; 95% confidence interval [CI] 1.95–20.5; p = 0.002), whereas BRCA2 mutation status was not (OR 0.45; 95% CI 0.02–2.67; p = 0.5). Conclusions: This study showed that BRCA1 mutation carriers with HR+/HER2− breast cancers have a higher rate of pCR than sporadic cancers and may derive greater benefit from chemotherapy. The use of NAC to downstage these patients should be considered. © 2023, Society of Surgical Oncology. |
| Keywords: | adult; controlled study; treatment response; middle aged; cancer surgery; gene mutation; major clinical study; genetics; mutation; doxorubicin; fluorouracil; paclitaxel; neoadjuvant therapy; methotrexate; cancer staging; breast cancer; epidermal growth factor receptor 2; tumor differentiation; cohort analysis; cyclophosphamide; pathology; breast neoplasms; brca1 protein; brca2 protein; retrospective study; age; breast tumor; neoadjuvant chemotherapy; taxane derivative; anthracycline; hormone receptor; brca; brca1 protein, human; pathologic complete response; brca2 protein, human; humans; human; female; article; hormone receptor positive breast cancer; human epidermal growth factor receptor 2 negative breast cancer |
| Journal Title: | Annals of Surgical Oncology |
| Volume: | 30 |
| Issue: | 13 |
| ISSN: | 1068-9265 |
| Publisher: | Springer |
| Date Published: | 2023-12-01 |
| Start Page: | 8412 |
| End Page: | 8418 |
| Language: | English |
| DOI: | 10.1245/s10434-023-14319-0 |
| PUBMED: | 37798552 |
| PROVIDER: | scopus |
| PMCID: | PMC10752194 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Minna K. Lee -- Source: Scopus |
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