Long-term outcomes of S-1 combined with low-dose docetaxel as neoadjuvant chemotherapy (N-1 study, phase II trial) in patients with operable 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/m2 orally on days 1–14) and DOC (40 mg/m2 intravenously on day 1) every 3 weeks for 4–8 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 nonpCR 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=0.0176). Specifically in triple-negative patients, the difference was significant (100% vs. 60.0%, p=0.0224). Multivariate analysis revealed that high TILs (≥2–3+) and NG 2–3 independently predicted pCR. Microarray data revealed that three 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.