Long-Term Outcomes of S-1 Combined With Low-Dose Docetaxel as Neoadjuvant Chemotherapy (N-1 Study, Phase II Trial) in Patients With Breast Cancer

Background: We previously reported that S-1 and low -dose docetaxel (DOC) (N-1 study, phase II trial) could be a well -tolerated and effective neoadjuvant chemotherapies (NACs) for patients with operable breast cancer. Herein, we analyzed the long-term outcomes and developed clinicopathological and molecular predictors of pathological complete response (pCR). Patients and Methods: Eighty-three patients received S-1 (40 mg/m 2 orally on days 1-14) and DOC (40 mg/m 2 intravenously on day 1) every 3 weeks for 4 to 8 cycles. Disease -free survival (DFS) and overall survival (OS) were analyzed for each population with a pCR status. To assess the relationship between pCR and clinicopathological factors such as tumor -infiltrating lymphocytes (TILs, 1 + < 10%, 2 + 10%-50%, and 3 + > 50%) and nuclear grade (NG), microarray was used to compare the microRNA profiles of the pCR and non-pCR groups using core needle biopsy specimens. Results: With a median follow-up duration of 99.0 (range, 9.0-129.0) months, the 5 -year DFS and OS rates were 80.7% and 90.9%, respectively. The 5 -year OS rate of the pCR group was significantly better than that of the nonpCR group (100% vs. 86.2%, p = .0176). Specifically, in triple -negative patients, the difference was significant (100% vs. 60.0%, p = .0224). Multivariate analysis revealed that high TILs ( >= 2-3 + ) and NG 2-3 independently predicted pCR. Microarray data revealed that 3 miRNAs (miR-215-5p, miR-196a-5p, and miR-196b-5p) were significantly upregulated in the pCR group. Conclusion: Our NAC regimen achieved favorable long-term outcomes and significantly improved OS in the pCR group. High TILs, NG 2-3, and some miRNAs may be predictors of pCR.