Homologous recombination deficiency (HRD) status to predict the efficacy and prognosis of platinum-based neoadjuvant chemotherapy in patients with triple-negative breast cancer.

Abstract

e12605 Background: Triple negative breast cancer (TNBC) is the most aggressive type of breast cancer, and the predictive role of homologous recombination deficiency (HRD) in TNBC treated with platinum-based neoadjuvant chemotherapy (NCT) is not well described. Here, we sought to assess the association of HRD with pathological complete response (pCR) and survival outcomes in TNBC patients treated with NCT. Methods: 123 patients with stage II to III TNBC received one type of NCT regimen, including paclitaxel followed by anthracycline and cyclophosphamide-based NCT, and platinum-based NCT were enrolled in this study. The optimal cutoff of HRD score was determined by the Youden’s index on the ROC curve. HRD status was defined by either HRD score ≥ threshold or BRCA1/2 [tumor BRCA (t BRCA) and/or germline BRCA (g BRCA)] mutation. Logistic regression analysis was used to analyze the relationship between HRD and pCR. The Kaplan-Meier method, log-rank test and Cox regression were used for survival analysis. Results: A total of 104 FFPE and paired blood samples were successfully profiled from the 123 patients. The optimal cutoff for the HRD score of 58 was calculated based on the maximum Youden index value (0.235). HRD-High (HRD-H) was defined by either HRD score ≥ 58 or BRCA1/2 mutation. Of the 104 patients, 11.54 % (12) demonstrated BRCA mutation (g BRCA1 = 4, g BRCA2 = 4, t BRCA1=2 and t BRCA2 = 2), and another 46.15% (48) demonstrated HRD-H. In univariate logistic regression analysis, HRD status was significantly associated with a better pCR (p = 0.025, OR = 3.071, 95% CI: 1.154-8.175). Patients with HRD-H (p = 0.0103) or BRCA1/2 mutation (p = 0.0199) were all associated with superior event-free survival (EFS). There was a trend toward improved distant disease-free survival (DDFS), breast cancer–specific survival (BCSS), and overall survival (OS) in patients with HRD-H or BRCA1/2 mutation compared with HRD-Low or BRCA1/2 wild-type, although the differences did not reach statistical significance. Homologous recombination repair (HRR)-related genes mutation status was only associated with EFS (p = 0.0458). In multivariate logistic regression, Stromal tumor-infiltrating lymphocytes (sTILs) (p = 0.033, OR = 3.134, 95% CI:1.096-8.963) and HRD status (p = 0.015, OR = 4.014, 95% CI: 1.306-12.332) were both significantly associated with pCR. Conclusions: TNBC patients with HRD-H or BRCA1/2 mutation were more likely to benefit from platinum-based standard NCT.