Combination Chemotherapy in Treating Women With Stage II or Stage IIIA Breast Cancer That Has Spread to the Lymph Nodes

OBJECTIVES:

• Compare the disease-free survival and overall survival in patients with node-positive or high-risk node-negative operable stage II or IIIA breast cancer treated with docetaxel or paclitaxel after doxorubicin and cyclophosphamide.
• Determine whether the weekly administration of paclitaxel or docetaxel for 12 weeks improves disease-free survival and overall survival when compared with the conventional schedule of every 3 weeks for 4 courses after doxorubicin and cyclophosphamide in this patient population.
• Compare the toxic effects of docetaxel and paclitaxel when administered weekly for 12 weeks versus every 3 weeks for 4 courses in these patients.
• Compare the toxicity of paclitaxel administered every 3 weeks for 4 courses or weekly for 12 weeks to that of docetaxel administered on the same schedules in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to estrogen receptor status (positive vs negative vs unknown), nodal status (0 positive nodes vs 1-3 positive nodes vs 4-9 positive nodes vs at least 10 positive nodes), tumor size (no more than 5 cm vs more than 5 cm vs unknown), and type of prior surgery (mastectomy vs breast conservation surgery). Patients are randomized to one of four treatment arms.

• Arm I: Patients receive doxorubicin IV and cyclophosphamide IV every 3 weeks for 4 courses (weeks 1-12). Beginning at week 13, patients receive paclitaxel IV over 3 hours every 3 weeks for 4 courses.
• Arm II: Patients receive doxorubicin and cyclophosphamide as in arm I. Beginning at week 13, patients receive paclitaxel IV over 1 hour weekly for 12 weeks.
• Arm III: Patients receive doxorubicin and cyclophosphamide as in arm I. Beginning at week 13, patients receive docetaxel IV over 1 hour every 3 weeks for 4 courses.
• Arm IV: Patients receive doxorubicin and cyclophosphamide as in arm I. Beginning at week 13, patients receive docetaxel IV over 1 hour weekly for 12 weeks.

Within 4 weeks after completion of chemotherapy, patients with estrogen and/or progesterone receptor positive tumors receive oral tamoxifen daily for 5 years.

After completion of all chemotherapy, patients with prior segmental mastectomy receive radiotherapy once daily 5 days per week for 5-6 weeks. Patients with prior modified radical mastectomy may receive radiotherapy after chemotherapy completion at the investigator's discretion.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 5,000 patients will be accrued for this study within 1.27 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed operable stage IIA, IIB, or IIIA adenocarcinoma of the breast with histologically involved lymph nodes (T1, 2, or 3; N1 or 2; M0) OR high-risk node-negative disease (T2 or 3; N0)

• Primary tumor at least 2.1 cm in diameter for node-negative disease
• Bilateral breast disease allowed if at least 1 primary tumor meets the criteria above
• Must have had at least 6 axillary lymph nodes removed at dissection and at least one node positive for metastasis OR
• Sentinel node biopsy negative for metastasis (sentinel node biopsy positive allowed if enrolled on American College of Surgery Trial Z0011 and have beenrandomized to receive no axillary dissection)

• Additional axillary nodes may be obtained provided they are also negative for metastasis
• Complete tumor removal by either a modified radical mastectomy or local excision plus axillary lymph node dissection (i.e., breast conservation therapy) or sentinel node biopsy

• Tumor-free margins at least 1 mm for both invasive and noninvasive carcinoma except for lobular carcinoma in situ (less than 1 mm allowed)
• Concurrent enrollment on American College of Surgery Trial Z0010, Z0011, or NSABP B-32 allowed
• Hormone receptor status:

• Estrogen receptor status positive, negative, or unknown

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT no greater than 2 times upper limit of normal

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No history of myocardial infarction
• No congestive heart failure
• No significant ischemic or valvular heart disease

Other:

• No other prior invasive malignancies within the past 5 years except curatively treated basal or squamous cell skin cancer or carcinoma in situ of the cervix
• No hypersensitivity to paclitaxel or docetaxel or other similarly formulated drugs (with Cremophor or polysorbate)
• Not pregnant or nursing
• Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for breast cancer

Endocrine therapy:

• Prior tamoxifen of no more than 4 weeks duration for breast cancer allowed
• Prior tamoxifen or other selective estrogen receptor modulator (SERM) for chemoprevention (e.g., Breast Cancer Prevention Trial) or for other indications (e.g., osteoporosis) allowed
• No concurrent tamoxifen or other SERMs

Radiotherapy:

• No prior radiotherapy for this malignancy
• At least 2 weeks since prior radiotherapy to the breast for ductal carcinoma in situ

Surgery:

• See Disease Characteristics
• Less than 84 days since prior surgical procedure to adequately treat primary tumor