In this multicenter, randomized phase III trial, node positive early breast cancer patients are randomly assigned to receive either 6 cycles of FEC (5-fluorouracil 600 mg/m2, epirubicin 60 mg/m2 and cyclophosphamide 600 mg/m2, on day 1, every three weeks) or 4 cycles of EP (epirubicin 90 mg/m2 and paclitaxel 175 mg/m2, on day 1, every three weeks). The primary study endpoint is overall survival (OS). Secondary endpoints include toxicity and event free survival (EFS).

At the time the Gruppo Oncologico Nord-Ovest- Mammella Intergruppo trial 5 (GONO-MIG5) was designed in 1996, paclitaxel was known to have efficacy in patients with advanced breast cancer, but its role was still to be established in the adjuvant setting. Therefore the GONO-MIG5 trial was designed to compare a standard anthracycline-containing chemotherapy regimen, i.e. 5fluorouracil, epirubicin, ciclophosphamide (FEC), given for 6 cycles to a new regimen containing both epirubicin and paclitaxel (EP), given concurrently, for 4 cycles. This latter regimen was chosen on the basis of the results obtained in metastatic breast cancer patients, where the combination of doxorubicin and paclitaxel was associated with more than 90% of objective response . Only four cycles of the new regimen were planned since the expected toxicity, particularly the cardiotoxicity, was high, and a short treatment duration was hoped to be the best strategy to obtain a favourable balance between the toxicity and the expected high efficacy.

Inclusion Criteria:

• Women with histologically confirmed breast cancer who had undergone radical mastectomy or breast-conserving surgery in addition to full ipsilateral axillary lymph node dissection
• Lymph node-positive disease with less than 10 involved axillary lymph nodes
• Surgery performed not more than 5 weeks before randomization
• ECOG performance status 0
• Absolute neutrophil count ≥ 2,000/mm³
• WBC ≥ 3,000/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 1.5 times ULN
• Postoperative regional radiotherapy limited to the remaining breast admitted for patients who received breast-conserving surgery
• Written informed consent

Exclusion Criteria:

• Prior or concurrent ipsilateral or contralateral invasive breast carcinoma within the last 10 years
• Metastatic disease, including metastasis in the ipsilateral supraclavicular lymph nodes
• Prior chemotherapy or prior cytotoxic regimens or prior hormonal therapy
• Pregnant or nursing
• Other serious medical illness requiring medication, uncontrolled infections
• Other malignancy except adequately treated, cone-biopsied in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin
• Recent myocardial infarction, congestive heart failure, or serious arrhythmia