• Objective response rate after completion of neoadjuvant therapy (4 courses) [ Designated as safety issue: No ]
  
• Toxicity after completion of neoadjuvant and adjuvant therapies [ Designated as safety issue: Yes ]
  

• Disease-free survival at 1, 2, and 5 years [ Designated as safety issue: No ]
  
• Overall survival at 1, 2, and 5 years [ Designated as safety issue: No ]
  

OBJECTIVES:

• Compare the objective response rate of women with locally advanced breast cancer treated with neoadjuvant docetaxel and carboplatin with vs without trastuzumab (Herceptin®).
• Compare the toxic effects of these regimens in these patients.
• Compare disease-free and overall survival in patients treated with these regimens.
• Determine the molecular characteristics of tumors that are responsible for drug susceptibility and drug interactions in patients treated with these regimens.
• Provide additional prognostic information about these patients for conventional pathology studies.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age, initial tumor size, tumor type (T_2 vs T_3 vs T_4), presence of clinically positive lymph nodes (yes vs no), and mother's family history (positive vs negative).

• Neoadjuvant therapy: All patients receive docetaxel IV over 1 hour and carboplatin IV over 30-60 minutes on day 1 or 2. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients who are HER2/neu positive are randomized to 1 of 2 concurrent trastuzumab (Herceptin®) treatment arms.

  • Arm I: Patients receive trastuzumab (concurrently with chemotherapy) IV over 30-90 minutes on days 1, 8, and 15. Trastuzumab repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients do not receive concurrent trastuzumab. Patients receive neoadjuvant chemotherapy only.
• Surgery: Within 3 weeks after completion of course 4 of neoadjuvant therapy, patients with responding disease undergo definitive surgery.
• Adjuvant therapy: Within 4-6 weeks after surgery, patients with responding disease receive 4 additional courses of docetaxel and carboplatin as during neoadjuvant chemotherapy. All HER2/neu positive patients also receive trastuzumab IV once weekly for 12 weeks and then every 3 weeks for 40 weeks (total of 52 weeks of trastuzumab therapy).

Within 6 weeks after adjuvant chemotherapy, patients undergo radiotherapy.

Estrogen-receptor positive patients receive oral tamoxifen once daily for 5 years.

Patients are followed annually for 5 years.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study within 4 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed infiltrating adenocarcinoma of the breast

  • Primary disease greater than 2 cm (T_2, T_3) OR skin and chest wall involvement (T_4)
  • Any N
  • No evidence of metastasis (M0)
  • Diagnosed within the past 3 months
• HER2/neu status determined by fluorescent in situ hybridization

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 to 80

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• At least 1 year

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic

• Bilirubin ≤ upper limit of normal (ULN)
• SGOT and SGPT ≤ 1.5 times ULN
• Alkaline phosphatase ≤ 1.5 times ULN

Renal

• Creatinine no greater than 2.0 mg/dL

Cardiovascular

• LVEF normal by MUGA or echocardiogram

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergy to polysorbate or castor oil
• No ongoing active infection
• No concurrent life-limiting disease
• No other malignancy within the past 5 years that could affect the diagnosis or assessment of breast cancer, except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix
• No grade 2 or greater pre-existing peripheral neuropathy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior trastuzumab (Herceptin®)
• No other prior or concurrent immunotherapy
• No prior or concurrent gene therapy

Chemotherapy

• No prior docetaxel
• No prior carboplatin
• No other prior or concurrent chemotherapy

Endocrine therapy

• No prior or concurrent antitumor hormonal therapy

Radiotherapy

• No prior radiotherapy to the involved breast
• No concurrent radiotherapy to an indicator lesion

Surgery

• Not specified

Other

• More than 5 years since any prior drug therapy for breast cancer
• No other concurrent experimental drugs
• No other concurrent anticancer treatment