Abstract P5-16-04: A randomized phase II neoadjuvant study comparing docetaxel and cyclophosphamide (TC) with 5-fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel (FEC-D) for hormone receptor-negative breast cancer: The Kanagawa breast oncology group (KBOG) 1101 study

Purpose: This study aimed to evaluate response to neoadjuvant chemotherapy (NAC) for patients with hormone receptor-negative (HR-negative) breast cancer (BC) to identify subtypes that require anthracycline treatment. Methods: In total, 103 patients with operable HR-negative BC were registered. They were randomely assigned to administration of 6 cycles of docetaxel (75mg/m2) and cyclophosphamide (600 mg/m2) (TC6) or 3 cycles of 5-fluorouracil (500 mg/m2), epirubicin (100mg/m2), and cyclophosphamide (500mg/m2) followed by 3 cycles of docetaxel (100mg/m2) (FEC-D). Cytokeratin (CK) 5/6 and EGFR expression were used to identify basal and non-basal triple-negative (TN) BC. The primary endpoint was pathological complete response (pCR); secondary endpoints were safety, breast-conserving surgery, disease-free survival, and overall survival. Predictive factors of pCR for each regimen were also evaluated. Results: The pCR rate was 36% for FEC-D and 25.5% for TC6, which did not differ significantly (P=0.265). When TN BC was subdivided into basal and non-basal subtypes, the pCR rate in the basal subtype was significantly lower for TC6 (13.6%) than for FEC-D (42.9%) (P=0.033), but did not significantly differ in the non-basal (TC6, 36.4%; FEC-D, 25.0%) and HER2-positive (TC6, 41.7%; FEC-D, 35.7%) cases. The relative dose intensities of epirubicin and docetaxel in FEC-D and docetaxel in TC6 were 96.3±13.0%, 93.5±14.6%, and 93.9±16.3% (mean±SD), respectively. Occurrence of grade ≥2 adverse events was significant in FEC-D-treated patients. Poor appetite (P The rates of breast-conserving surgery were 68.0 and 72.3% for FEC-D and TC6, respectively (P=0.641). Patients achieved pCR had better DFS (log rank test, P = 0.287) and OS (log rank test, P = 0.069), though not significant. Patients treated with FEC-D had better DFS (log rank test, P = 0.107) and OS (log rank test, P = 0.159), though not significant. Among patients with TN BC, those treated with FEC-D had significantly better DFS (log rank test, P = 0.016) and OS (log rank test, P = 0.034) than treated with TC6. Low ALDH1 expression and high topo IIα protein expression were strongly correlated with pCR in FEC-D, with odds ratios (ORs) of 4.33 [95% CI, 1.02–18.38] and 4.08 [0.97–17.2], respectively. ALDH1 was also associated with pCR in TC, OR=3.50 [0.84–14.6]. Other factors, including age, tumor size, nodal status, tumor grade, Ki67, p53, and TOP2A status were not associated with pCR in either regimen. Conclusions:We found that TC6 was less effective than FEC-D for treating HR-negative BC because it was insufficient for TNBC, particularly for basal BC. This suggests that anthracycline is more important than taxane for basal BC. Additionally, ALDH1 could be a marker for resistance to conventional chemotherapy. Citation Format: Narui K, Ishikawa T, Shimizu D, Tanabe M, Sasaki T, Oba MS, Morita S, Nawata S, Kida K, Mogaki M, Doi T, Tsugawa K, Ogata H, Ota T, Kosaka Y, Sengoku N, Kuranami M, Saito Y, Suzuki Y, Suto A, Arioka H, Chishima T, Ichikawa Y, Endo I, Tokuda Y. A randomized phase II neoadjuvant study comparing docetaxel and cyclophosphamide (TC) with 5-fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel (FEC-D) for hormone receptor-negative breast cancer: The Kanagawa breast oncology group (KBOG) 1101 study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-04.