title: Phase II study of preoperative systemic treatment with the combination of docetaxel and trastuzumab in patients with locally advanced HER-2-overexpressing breast cancer.
abstract: We conducted a phase II study using docetaxel and trastuzumab as preoperative systemic treatment for locally advanced HER-2-overexpressing breast cancer (stage IIIB or IIIC) to evaluate the efficacy and safety, and to perform a subset analysis based on tumor biomarkers. Patients received 4 mg/kg trastuzumab on day 1, followed by weekly treatments of 2mg/kg, in addition to 75 mg/m(2) docetaxel every 3 weeks for 4 cycles before surgery. The primary end point was clinical response rate measured by MRI or CT. Twenty-five patients were enrolled. The median age was 54 years and median tumor size was 63 mm. The overall clinical response rate was 68% [95% CI: 47-85%] and the pCR rate was 22% [95% CI: 8-44%]. The clinical response and the pCR rates of patients with ER- and PgR- tumors were 79% and 31%, respectively, while they were 55% and 10%, respectively, in the patients with ER+ and/or PgR+ tumors (p=0.34, p=0.34, respectively). Cardiac toxicity was well tolerated; there was no evidence of clinical cardiac events in any patient. The combination of docetaxel and trastuzumab produced highly favorable clinical and pathological responses for locally advanced HER-2-overexpressing breast cancer. Subgroup analysis suggests that ER/PgR negative tumors might be associated with pathological response in locally advanced breast cancer.
authors.affiliation: Tokai Breast Cancer Clinical Research Group, Department of Breast and Endocrine Surgery, Nagoya University School of Medicine, Aichi, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Sawaki
authors.forename: Hiroji
authors.initials: H
authors.lastname: Iwata
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sato
authors.forename: Masaki
authors.initials: M
authors.lastname: Wada
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Toyama
authors.forename: Eiichi
authors.initials: E
authors.lastname: Sasaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Imai
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human