Randomized Phase II Study of Primary Systemic Chemotherapy and Trastuzumab for Operable HER2 Positive Breast Cancer

Abstract

Background In primary systemic therapy in patients with human epidermal growth factor receptor 2 positive (HER2 +) breast cancer, improvements in pathologic complete response (pCR) rate have been achieved by administering trastuzumab. Patients and Methods Patients with stage II or IIIA HER2 + operable breast cancer were randomly assigned to receive four 3-weekly cycles of FEC (5-fluorouracil 500 mg/m 2, epirubicin 100 mg/m 2, cyclophosphamide 500 mg/m 2) followed by 4 cycles of 3-weekly trastuzumab (8 mg/kg week 1 and then 6 mg/kg) with either 12 weekly doses of paclitaxel 80 mg/m 2 (FEC-PH) or 4 cycles of 3-weekly docetaxel 75 mg/m 2 (FEC-DH). Results Between March 2007 and June 2008, 102 patients were enrolled. Forty-nine patients receiving FEC-PH and 47 receiving FEC-DH were assessable for efficacy and safety. Eighty-four patients completed treatment and underwent surgery. There was no significant difference in the pCR rate between the 2 groups (46.9% [95% CI, 33.7%-60.6%] with FEC-PH vs. 42.6% [95% CI, 29.5%-56.8%] with FEC-DH; P = .67). Analysis by hormone receptor (HR) status showed pCR rates of 54.2% (32/59) in HR − tumors and 29.7% (11/37) in HR + tumors ( P = .02). Among HR − tumors, the pCR rates were 65.4% and 45.5% in patients treated with FEC-PH and FEC-DH, respectively ( P = .13). Conclusions There was no significant difference in pCR rate between FEC-PH and FEC-DH. Both regimens achieved higher pCR rates in HR − than HR + breast cancer, and there was a trend toward higher pCR in HR − tumors with FEC-PH compared with FEC-DH. Further investigation is warranted to explore the relationship between efficacy and HR status.