Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer

Inclusion Criteria

• The patient must consent to participate in the study and must have signed an approved consent form conforming with federal and institutional guidelines.
• The patient must have a life expectancy of at least 10 years and a Zubrod performance status of 0 or 1. (Comorbid conditions but not the diagnosis of breast cancer should be taken into consideration when determining life expectancy.)
• The interval between the last surgery for breast cancer staging or treatment and randomization must be no more than 84 days.
• The tumor must be invasive carcinoma of the breast on histologic examination.
• All of the following staging criteria must be met:
• By clinical and pathologic evaluation, primary tumor must be T1-3;
• By clinical evaluation, ipsilateral nodes must be cN0, cN1, or cN2a;
• By pathologic evaluation, ipsilateral nodes must be pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN3a, or pN3b (only if due to microscopic involvement of internal mammary node detected by sentinel lymph node dissection and with more than 3 positive axillary lymph nodes).
• Patients must have an estrogen receptor (ER) analysis performed on the primary tumor prior to randomization. If ER analysis is negative, then progesterone receptor (PgR) analysis must be performed. If ER analysis is positive, PgR analysis is desired, but not mandatory. ("Marginal" or "borderline" results [i.e., those not definitely negative] will be considered positive regardless of the methodology used.)
• Patients must have had either a lumpectomy or a total mastectomy. Patients must have completed one of the following procedures for evaluation of pathologic nodal status.
• Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes (This approach is strongly recommended.)
• Sentinel lymphadenectomy alone if one of the following criteria is met:
• Pathologic nodal staging based on sentinel lymphadenectomy is pN1mi or pN1b
• Surgeon elects not to remove additional non-sentinel nodes (This approach is strongly discouraged, but will not preclude participation in B-38.)
• Axillary lymphadenectomy without sentinel node isolation procedure.
• Patients must have no clinical or radiologic evidence of metastatic disease.
• Patients with either skeletal pain or alkaline phosphatase that is greater than ULN but less than or equal to 2.5 x ULN are eligible for inclusion in the study if bone scans fail to demonstrate metastatic disease. Suspicious findings on bone scan must be confirmed as benign by x-ray, MRI, or biopsy.
• Patients with aspartate transaminase (AST) or alkaline phosphatase greater than ULN are eligible for inclusion in the study if liver imaging fails to demonstrate metastatic disease and the following requirements are met at the time of randomization.
• Postoperative absolute granulocyte count (AGC) must be greater than or equal to 1200/mm3.
• Postoperative platelet count must be greater than or equal to 100,000/mm3.
• The following criteria for postoperative evidence of adequate hepatic function must be met:
• total bilirubin must be less than or equal to ULN for the lab unless the patient has a grade 1 bilirubin elevation (greater than ULN to 1.5 x ULN) due to Gilbert's disease or similar syndrome due to slow conjugation of bilirubin; and
• alkaline phosphatase must be less than or equal to 2.5 x ULN for the lab; and
• the AST must be less than or equal to 1.5 x ULN for the lab; and
• alkaline phosphatase and AST cannot both be greater than ULN.
• Postoperative serum creatinine must be less than or equal to ULN.
• At the time of randomization, the patient must have had the following: history and physical exam, EKG, and imaging of the chest within the past 3 months and bilateral mammogram within the past 6 months.
• Within 3 months prior to entry, the patient must have a baseline left ventricular ejection fraction (LVEF), measured by Multiple Gated Acquisition (MUGA) scan or echocardiogram, greater than or equal to lower limit of no