The present study aimed at evaluating whether a weekly cisplatin, epirubicin, and paclitaxel (PET) regimen could increase the pathological complete response (pCR) rate in comparison with a tri-weekly epirubicin and paclitaxel administration in locally advanced breast cancer (LABC) patients. Patients with stage IIIB disease were randomised to receive either 12 weekly cycles of cisplatin 30 mg m(-2), epirubicin 50 mg m(-2), and paclitaxel 120 mg m(-2) (PET) plus granulocyte-colony stimulating factor support, or four cycles of epirubicin 90 mg m(-2)+paclitaxel 175 mg m(-2) (ET) every 3 weeks. Overall, 200 patients (PET/ET=100/100) were included in this study. A pCR in both breast and axilla occurred in 16 (16%) PET patients and in six (6%) ET patients (P=0.02). The higher activity of PET was evident only in ER negative (27.5 vs 5.4%; P=0.026), and in HER/neu positive (31 vs 5%; P=0.037) tumours. The two arms yielded similar pCR rate in ER positive (PET/ET=7.5/7.1%) and HER/neu negative (PET/ET=10/6%) patients. At a 39 months median follow-up, 70 patients showed a progression or relapses (PET, 32 vs ET, 38). Anaemia, mucositis, peripheral neuropathy, and gastrointestinal toxicity were substantially more frequent in the PET arm. The PET weekly regimen is superior to ET in terms of pCR rate in LABC patients with ER negative and/or HER2 positive tumours Mature data in terms of disease-free and overall survival are needed to ascertain whether this approach could improve the prognosis of these subsets of LABC patients.