Abstract
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/m2 and cyclophosphamide 600 mg/m2, four cycles every 3 weeks) followed by docetaxel (75 mg/m2, 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.
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Acknowledgments
The authors would like to thank the Translational Research Informatics Center (Director Masanori Fukushima, MD, PhD), Takako Jyono, Yasuyo Kusunoki, and Kotone Matsuyama for their excellent technical support. Trastuzumab to be used preoperatively in combination with chemotherapy was supplied by Chugai Pharmaceutical Co., Ltd. HER2NAT was sponsored by Chugai Pharmaceutical. Chugai Pharmaceutical also funded medical writing support provided by Tim Kelly.
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The authors declare no conflicts of interest.
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Aogi, K., Saeki, T., Nakamura, S. et al. 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). Int J Clin Oncol 18, 598–606 (2013). https://doi.org/10.1007/s10147-012-0437-1
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DOI: https://doi.org/10.1007/s10147-012-0437-1