Combination Chemotherapy With or Without Trastuzumab in Treating Patients With Stage II or Stage III Breast Cancer

OBJECTIVES:

Primary

• Compare 2 neoadjuvant chemotherapy regimens (docetaxel, doxorubicin hydrochloride, and cyclophosphamide [TAC] vs doxorubicin and cyclophosphamide followed by paclitaxel and carboplatin [ACAC]), in terms of toxicities and effectiveness as defined by the pathological complete remission rate, in patients with non HER2/neu overexpressing stage II or III breast cancer.
• Evaluate the probability of achieving a pathological complete remission when adding trastuzumab (Herceptin®) to ACAC in the subset of patients with HER2/neu overexpressing stage II or III breast cancer.

Secondary

• Identify prognostic and predictive markers of outcome, recurrence, and targets of therapy.

OUTLINE: This is a randomized study. Patients with non HER2/neu overexpressing tumors are randomized to 1 of 2 treatment arms. Patients with HER2/neu overexpressing tumors are assigned to arm III.

• Arm I: Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and docetaxel IV on day 1. Treatment repeats every 21 days for 6 courses.
• Arm II: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; treatment repeats every 2 weeks for 4 courses. Patients then receive carboplatin IV on day 1 and paclitaxel IV on days 1, 8, and 15; treatment with carboplatin and paclitaxel repeats every 4 weeks for 3 courses.
• Arm III: Patients receive chemotherapy as in arm II. They also receive trastuzumab (Herceptin®) IV weekly, beginning with the first doses of paclitaxel and carboplatin.

Within 4 weeks after completion of chemotherapy with or without trastuzumab (Herceptin®), all patients undergo surgery.

PROJECTED ACCRUAL: A total of 105 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically proven infiltrating ductal or lobular breast carcinoma

• Stage II or III disease
• Inflammatory breast cancer allowed
• Hormone-receptor status not specified

PATIENT CHARACTERISTICS:

• ECOG performance status < 2
• Male or female
• Menopausal status not specified (for female patients)
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin normal (except for patient's with Gilbert's disease)
• Creatinine ≤ 1.2 mg/dL
• Creatinine clearance ≥ 70 mL/min
• Ejection fraction ≥ 50% on MUGA
• No neuropathy ≥ grade 1
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective nonhormonal contraception
• No prior malignant disease within the past 5 years, excluding:

• Squamous cell or basal cell skin carcinoma
• Stage I or in situ cervical carcinoma
• No noninvasive (in situ) breast carcinoma within the past 5 years

PRIOR CONCURRENT THERAPY:

• At least 5 years since prior antiestrogen treatment for any indication other than breast cancer prevention (tamoxifen, raloxifene, or an aromatase inhibitor)
• No prior radiotherapy to the chest wall