Phase II clinical trial of S-1 and paclitaxel in combination followed by 5-fluorouracil/epirubicin/cyclophosphamide (FEC) as neoadjuvant treatment for HER2-negative, stage II/III breast cancer: 10-year follow-up results.

e12605 Background: The sequential combination of anthracyclines and taxanes is a standard in the neoadjuvant and adjuvant settings for breast cancer. Preclinical studies demonstrate synergy between 5-FU and taxanes, with survival benefits in metastatic breast cancer. S-1, an oral fluoropyrimidine derivative, inhibits dihydropyrimidine dehydrogenase, reducing gastrointestinal toxicity. This study evaluated the efficacy and safety of neoadjuvant S-1/paclitaxel followed by FEC in HER2-negative, Stage II/III breast cancer. Methods: This was an open-label, single-arm, phase II, single-center, clinical study conducted at Teikyo University Hospital, Japan. The study was conducted in accordance with the Declaration of Helsinki, and the study protocol was approved by the Institutional Review Board of Teikyo University School of Medicine. Patients provided written informed consent before entering the study. Patients with HER2-negative Stage II/III breast cancer received 4 cycles of S-1 (80 mg/m²/day, days 1–14) and paclitaxel (60 mg/m², days 1, 8, and 15 every 4 weeks), followed by 4 cycles of FEC (5-FU 500 mg/m², epirubicin 90 mg/m², cyclophosphamide 500 mg/m² on day 1 every 3 weeks). The primary endpoint was the pathological complete response (pCR), while secondary endpoints included histological treatment effect, safety evaluation, and clinical tumor response. Results: Between November 2006 and December 2014, 38 patients were enrolled. The median age was 50.8 years (range: 29–69), and the median tumor size was 3.0 cm (range: 0.9–10 cm). A total of 27 patients (71.1%) were clinically node-positive, and 30 patients (78.9%) were hormone receptor (HR)-positive. The overall clinical response rate was 84.2%, with 12 complete responses and 20 partial responses. The clinical complete response (cCR) rate was 20.0% in HR-positive tumors and 25.0% in HR-negative tumors. No patients experienced clinical progression during therapy. The pCR rate was 21.1% (8/38), with higher rates in HR-negative tumors compared to HR-positive tumors (25.0% vs. 20.0%; p > 0.05). Breast conservation was achieved in 30 patients (78.9%). After a median follow-up of 98 months, 10 patients experienced recurrence. Disease-free survival was estimated at 73.7%, and overall survival at 84.2%. Grade 3/4 febrile neutropenia occurred in 5.3% of patients, with no grade 3/4 non-hematologic adverse events reported. The most common non-hematologic adverse drug reaction was alopecia (97.4%), followed by peripheral neuropathy (73.7%). Median relative dose intensities were 0.984 for FEC, 0.983 for paclitaxel, and 0.987 for S-1. Conclusions: The combination of S-1/paclitaxel followed by FEC is a well-tolerated and effective neoadjuvant therapy for HER2-negative, HR-positive Stage II/III breast cancer.