A Three-Arm Randomized Trial to Compare Adjuvant Adriamycin and Cyclophosphamide Followed by Taxotere (AC-T); Adriamycin and Taxotere (AT); and Adriamycin, Taxotere, and Cyclophosphamide (ATC) in Breast Cancer Patients With Positive Axillary Lymph Nodes

Date de début de l'étude : 1 mars 1999

DISEASE CHARACTERISTICS: Histologically confirmed invasive adenocarcinoma of the breast Confined to the breast and ipsilateral axilla on clinical exam Stage I, II, or IIIA (cT1-3, N0-1, M0) At least one axillary lymph node with evidence of tumor on histologic exam Sentinel node biopsy allowed if followed by axillary dissection No suspicious palpable nodes in the contralateral axilla or palpable supraclavicular or infraclavicular nodes, unless proven on biopsy to not be involved with tumor No bilateral malignancy or mass in the opposite breast, unless mass is histologically proven to be benign Must have undergone either a prior total mastectomy and axillary dissection (modified radical mastectomy) OR Prior lumpectomy and axillary dissection Patients must receive radiotherapy after randomization (not before) AND after chemotherapy Margins must be clear No ipsilateral lymph nodes that are fixed to one another or to other structures (N2 disease) and/or any positive nonaxillary lymph nodes (intramammary nodes are considered axillary nodes) No histologically evident invasive tumor or ductal carcinoma in situ No diffuse tumors by mammography that would not be surgically amenable to lumpectomy No other dominant mass in the ipsilateral breast remnant unless one of the following is true: Histologically benign Surgically removed with clear margins if malignant No ulceration, erythema, infiltration of the skin or underlying chest wall (complete fixation), peau d'orange, or skin edema of any magnitude Tethering or dimpling of the skin or nipple inversion allowed No metastatic disease Skeletal pain allowed if bone scan negative for metastases Hormone receptor status: Estrogen and progesterone status determined PATIENT CHARACTERISTICS: Age: greater than or equal to 18 years Sex: Female Menopausal status: Not specified Performance status: Not specified Life expectancy: At least 10 years, excluding diagnosis of cancer Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 (may be less, if in the opinion of the investigator, this represents an ethnic or racial variation) Platelet count at least 100,000/mm^3* NOTE: *If platelet count is above the upper limit of normal (ULN), significant underlying hematologic disorders must be excluded Hepatic: Bilirubin no greater than ULN Alkaline phosphatase less than 2.5 times ULN* SGOT less than 1.5 times ULN* No nonmalignant systemic hepatic disease that would preclude study participation NOTE: *Alkaline phosphatase and SGOT cannot both be greater than ULN Renal: Creatinine no greater than normal No nonmalignant systemic renal disease that would preclude study participation Cardiovascular: No nonmalignant systemic cardiovascular disease that would preclude study participation LVEF at least lower limit of normal (LLN) by MUGA or echocardiogram No active cardiac disease that would preclude use of doxorubicin or docetaxel, including the following: Any prior myocardial infarction Angina pectoris requiring anti-anginal medication History of congestive heart failure Cardiac arrhythmia requiring medication Severe conduction abnormality Valvular disease with documented cardiac function compromise Cardiomegaly on chest x-ray or ventricular hypertrophy on EKG, unless LVEF at least LLN Poorly controlled hypertension (diastolic greater than 100 mm/Hg) Hypertension well controlled by medication allowed Other: No grade 2 or greater peripheral neuropathy No other prior malignancy within the past 5 years except: Effectively treated squamous cell or basal cell skin cancer Surgically treated carcinoma in situ of the cervix Segmentally resected lobular carcinoma in situ of the ipsilateral or contralateral breast Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception No nonmalignant systemic disease that would preclude study participation No diabetes with morning fasting blood glucose of 200 mg/dL or greater No psychiatric or addictive disorders that would preclude informed consent No contraindication to corticosteroids that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy: No prior immunotherapy for breast cancer Chemotherapy: No prior chemotherapy for breast cancer No prior anthracyclines or taxanes No other concurrent investigational chemotherapy Endocrine therapy: No prior hormonal therapy for breast cancer No concurrent hormonal birth control methods or other hormonal therapy No concurrent raloxifene, including for osteoporosis Concurrent low-dose topical estrogen in the form of conjugated estrogen ring or conjugated estrogen vaginal cream (dose no more than 0.3 mg or 1/8 of an applicator applied vaginally 3 times a week) allowed Radiotherapy: See Disease Characteristics No prior radiotherapy for this malignancy Surgery: See Disease Characteristics No more than 84 days since prior surgery for breast cancer (e.g., lumpectomy, mastectomy, sentinel node biopsy, axillary dissection, or re-excision of lumpectomy margins) Other: No prior systemic therapy for this malignancy No concurrent medications that alter cardiac conduction (e.g., digitalis, beta blockers, or calcium-channel blockers) for cardiac arrhythmia, angina, or congestive heart failure (allowed if administered for other reasons [e.g., hypertension]) Concurrent bisphosphonates allowed