title: 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).
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/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.
authors: Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minami-umemoto-machi, Matsuyama, Ehime, 791-0280, Japan. kaogi@shikoku-cc.go.jp
authors: Kenjiro
authors: K
authors: Aogi
authors: Toshiaki
authors: T
authors: Saeki
authors: Seigo
authors: S
authors: Nakamura
authors: Masahiro
authors: M
authors: Kashiwaba
authors: Nobuaki
authors: N
authors: Sato
authors: Norikazu
authors: N
authors: Masuda
authors: Yoshiaki
authors: Y
authors: Rai
authors: Shinji
authors: S
authors: Ohno
authors: Katsumasa
authors: K
authors: Kuroi
authors: Reiki
authors: R
authors: Nishimura
authors: Keiko
authors: K
authors: Miyakoda
authors: Futoshi
authors: F
authors: Akiyama
authors: Masafumi
authors: M
authors: Kurosumi
authors: Tadashi
authors: T
authors: Ikeda
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003520:Cyclophosphamide; D000077143:Docetaxel; D015251:Epirubicin; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human