Adjuvant Trastuzumab vs Observation in Locally Advanced Breast Cancer Treated With Neoadjuvant Trastuzumab

OBJECTIVES: Primary * To determine the percentage of pathological responses in patients with stage II or III breast cancer treated with neoadjuvant therapy comprising fluorouracil, doxorubicin hydrochloride, and cyclophosphamide followed by trastuzumab (Herceptin®) and paclitaxel. * To compare the disease-free survival of patients treated with adjuvant therapy comprising trastuzumab versus observation. Secondary * To measure the overall survival at 3 years in these patients. * To measure the cardiac safety profile of these regimens in these patients. * To measure the percentage of patients that become negative on the fluorescence in situ hybridization (FISH) test at the end of neoadjuvant therapy. OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms. * Arm I : * Neoadjuvant therapy: Patients receive fluorouracil IV, doxorubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive trastuzumab (Herceptin®) IV over 30-90 minutes and paclitaxel IV over 1 hour once a week for 12 weeks. After completion of neoadjuvant therapy, patients proceed to surgery. * Surgery: Patients undergo definitive surgery. Some patients may also undergo radiotherapy\*. NOTE: \*Patients with initial tumor > 5 cm, inflammatory breast cancer, or with a skin condition or final pathological evaluation of metastasis to > 4 nodes or 1-3 nodes with capsular ruptures or extension to fatty tissues receive adjuvant radiotherapy. * Adjuvant therapy: Beginning 4 weeks after surgery, patients receive trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for 13 courses. * Arm II: * Neoadjuvant therapy: Patients receive neoadjuvant therapy as in arm I. * Surgery: Patients undergo definitive surgery. Some patients may also undergo radiotherapy if clinically indicated. * Observation: Beginning 4 weeks after surgery, patients undergo observation. In both arms, patients with estrogen receptor- and/or progesterone receptor-positive disease also receive anastrozole daily for 5 years. Premenopausal patients with remaining ovarian function (as confirmed by follicle-stimulating hormone \[FSH\] and estradiol) after completion of anastrozole undergo chemical or surgical ovarian ablation. After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then once a year thereafter. PROJECTED ACCRUAL: A total of 160 patients (80 per treatment arm) will be accrued for this study.