Comparison of outcomes of neoadjuvant chemotherapy in BRCA1- versus BRCA2-associated breast and ovarian cancers
Aim: BRCA1/2-associated breast and ovarian carcinomas are often regarded as a single entity, assuming that BRCA1 and BRCA2 genes are almost equivalent with regard to their clinical significance. However, BRCA1 and BRCA2 genes differ in their function; therefore, a comparison of treatment outcomes in...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Open Exploration Publishing Inc.
2025-06-01
|
| Series: | Exploration of Targeted Anti-tumor Therapy |
| Subjects: | |
| Online Access: | https://www.explorationpub.com/uploads/Article/A1002325/1002325.pdf |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Aim: BRCA1/2-associated breast and ovarian carcinomas are often regarded as a single entity, assuming that BRCA1 and BRCA2 genes are almost equivalent with regard to their clinical significance. However, BRCA1 and BRCA2 genes differ in their function; therefore, a comparison of treatment outcomes in BRCA1 vs. BRCA2 carriers is warranted. Methods: This study focused on consecutive patients treated with neoadjuvant chemotherapy (NACT), given that these subjects are treatment-naive and accessible for immediate assessment of pathological and clinical outcomes. Results: BRCA2-associated high-grade serous ovarian carcinomas (HGSOCs) demonstrated significantly higher rates of pathologic complete response (pCR) as compared to BRCA1-related cancers [8/15 (53%) vs. 7/48 (15%), P = 0.004]. In contrast, HER2-negative breast cancer (BC) patients showed a numerically higher rate of pCR in BRCA1 vs. BRCA2 mutation carriers [38/69 (55%) vs. 13/36 (36%), P = 0.1]. However, the comparison with BRCA-wild-type (WT) tumors revealed that this tendency was mainly attributed to the increased prevalence of hormone receptor (HR)-negative disease in the former group. When BC patients were stratified according to the tumor receptor status, the response rates in triple-negative patients were consistently higher than in HR+/HER2– patients across all analyzed subgroups [BRCA1: 35/59 (59%) vs. 3/10 (30%); BRCA2: 5/10 (50%) vs. 8/26 (31%); WT: 31/76 (41%) vs. 12/74 (16%); Mantel-Haenzsel P < 0.001]. Logistic regression analysis revealed that the odds ratio (OR) for achieving pCR was higher for receptor status (triple-negative vs. HR+: OR = 3.4, 95% CI 1.9–6.0, P < 0.001) than for BRCA status (any mutation vs. WT: OR = 2.1, 95% CI 1.2–3.6, P = 0.008). The addition of carboplatin did not improve pCR rates in BRCA1- or BRCA2-associated BCs, while there was a numerically higher efficacy of carboplatin-containing regimens in patients with WT triple-negative tumors [14/26 (54%) vs. 15/44 (34%), P = 0.13]. Conclusions: Hereditary ovarian carcinomas demonstrate better NACT outcomes in BRCA2 vs. BRCA1 mutation carriers. The opposite trend is observed in BC, which is likely to be attributed to a high frequency of triple-negative disease in BRCA1- but not BRCA2-associated BCs. Triple-negative receptor status rather than BRCA1/2 status is the strongest predictor of response to NACT in BC. |
|---|---|
| ISSN: | 2692-3114 |