Fifty patients with stage IIIB and IV breast cancer entered a prospective study receiving combination chemotherapy consisting of mitoxantrone (8 mg/m2) on day 1, methotrexate (30 mg/m2) on day 1, vincristine (1 mg/m2) on day 2, and carboplatine (250 mg/m2) on day 2 (MIMOC), plus cyclical hormonotherapy with tamoxifen (20 mg daily, days 1-10) and megestrol acetate (160 mg daily, days 11-21). The regimen was repeated every 3 weeks. None had received chemotherapy for advanced disease, although 17 patients had previously received adjuvant chemotherapy and 21 had received adjuvant hormonotherapy with tamoxifen. Twenty-seven patients had positive estrogen receptor (ER+) status, and 23 negative estrogen receptor (ER-) status. Response was observed in 31 (62%) of the 50 analyzed patients (95% CI: 48.5-75.4%), with 5 complete responses (10%). A significantly better response rate was observed in ER+ patients (p = 0.03). The median duration of response was 16 months, and the median time to disease progression was 18 months. The median overall survival was 19 months (27 for responders and 7 for nonresponders). ER+ patients had a higher probability of survival (p = 0.02). Toxicity was moderate. Nausea/vomiting and myelotoxicity were the main side effects. In conclusion, MIMOC plus cyclical hormonotherapy represents a well-tolerated and effective first-line treatment for advanced breast cancer. The observed difference in response and survival in favor of ER+ patients warrants further investigation.