A Multicenter, Phase II Study of Epirubicin/cyclophosphamide Followed by Docetaxel and Concurrent Trastuzumab As Primary Systemic Therapy for HER-2 Positive Advanced Breast Cancer (the HER2NAT Study)

Background: The outcome in patients with human epidermal growth factor receptor-2 (HER-2)-positive locally advanced breast cancer may be improved by integrating trastuzumab with primary systemic therapy (PST).

Methods: The efficacy and safety of PST comprising EC (epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2), four cycles every 3 weeks) followed by docetaxel (75 mg/m(2), four cycles every 3 weeks) and concurrent trastuzumab (loading dose 4 mg/kg followed by 2 mg/kg, 12 cycles every week) was investigated in a multicenter, prospective, phase II study in patients with HER-2-positive stage IIIB/IIIC/IV breast cancer. The primary endpoint was pathologic complete response (pCR) including the tumor intraductal component confirmed by central pathologic review.

Results: In total, 38 patients were enrolled (stage IIIB, 63.2 %; IIIC, 23.7 %; IV, 13.2 %; estrogen receptor- and/or progesterone receptor-positive, 47.4 %). The pCR rate was 16.2 % in the primary tumor (six of 37 patients in the Full Analysis Set) and 56.8 % (21/37) in the ipsilateral axillary lymph nodes. Treatment was given according to protocol in 28 of 37 patients; six of 28 in the Per-Protocol Set achieved pCR (21.4 %). The clinical response rate was 67.6 % (25/37 patients; complete response, 13.5 %; partial response, 54.1 %). No patients developed congestive heart failure; however, three patients had a non-symptomatic decrease of >10 % of left ventricular ejection fraction.

Conclusions: PST including concurrent use of trastuzumab combined with docetaxel is effective and well-tolerated in HER-2-positive advanced breast cancer patients, including those patients requiring mastectomy for local control.