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

Inclusion Criteria

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