Randomized Phase Ii Clinical Trial And Biomarker Analysis Of Paclitaxel Plus Epirubicin Versus Vinorelbine Plus Epirubicin As Neoadjuvant Chemotherapy In Locally Advanced Her2-Negative Breast Cancer Withtekt4variations

Purpose Resistance to paclitaxel remains a major challenge in treating breast cancer. Our preclinical study suggested thatTEKT4germline variations in breast cancer are associated with paclitaxel resistance and increase vinorelbine sensitivity. This clinical trial compared the efficacy of paclitaxel and vinorelbine in breast cancer neoadjuvant chemotherapy. Methods In this open-label, single-center, phase II trial, female patients with human epidermal growth factor receptor 2 (HER2)-negative, stage IIB-IIIC breast cancer harboringTEKT4germline variations were randomly assigned to the paclitaxel plus epirubicin (PE) or vinorelbine plus epirubicin (NE). The primary endpoint was the pathologic complete response (pCR) rate, and the secondary endpoints were the objective response rate (ORR) and safety. Targeted sequencing of a panel comprising 484 breast-related genes was performed to identify pCR-associated somatic mutations in each group. Results 91 Patients were assigned to PE (46 patients) or NE (45 patients). NE numerically increased the pCR rate (22.2% versus 8.7%,P = 0.074). The ORRs for NE and PE were 82.2% and 76.1%, respectively. Interestingly, NE (15.4%) showed a significantly higher pCR rate than PE (0%) in the hormone receptor (HR)-positive subgroup (P = 0.044). Both regimens were well tolerated, with grade 3 and 4 toxicities reported at the expected levels. The biomarker analysis showed thatUNC13Dmutation predicted the pCR rate in NE (P = 0.011). Conclusions Although the primary endpoint was not met, NE might bring clinical benefit to HR-positive patients or patients simultaneously carryingUNC13Dmutations.