• Complete pathological response after 4 courses [ Designated as safety issue: No ]
  

• Survival [ Designated as safety issue: No ]
  
• Disease-free survival [ Designated as safety issue: No ]
  
• Effect of prognostic factors [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Compare the complete pathological response rate in women with poor-risk early breast cancer treated with neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel with vs without gemcitabine.

Secondary

• Compare the disease-free and overall survival of patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare the effect of these regimens on prognostic factors in these patients.
• Correlate molecular profiles, specific gene mutations, and genomic and gene expression changes with clinical outcome in these patients.
• Compare the quality of life of patients treated with these regimens.
• Determine the health economics associated with this study.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to estrogen-receptor status (negative vs greater than 10% positive cells), HER-2 status (positive vs negative), tumor size (30-50 mm vs greater than 50 mm), and clinical involvement of axillary nodes (yes vs no). Patients are randomized to 1 of 4 treatment arms.

• Neoadjuvant sequential chemotherapy:

  • Arm I: Patients receive epirubicin IV and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients then receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for 4 courses.
  • Arm II: Patients receive paclitaxel as in arm I followed by epirubicin and cyclophosphamide as in arm I.
  • Arm III: Patients receive epirubicin and cyclophosphamide as in arm I followed by paclitaxel as in arm I and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 4 courses.
  • Arm IV: Patients receive paclitaxel as in arm I and gemcitabine as in arm III followed by epirubicin and cyclophosphamide as in arm I.
• Surgery: After completion of neoadjuvant chemotherapy, patients in all arms undergo definitive surgery.

Tumor tissue is removed from a subset of patients during serial biopsies. Molecular and genetic profiling, mutation analysis, and comparative genomic analysis is performed on the tissue samples.

Quality of life is assessed at baseline, after 4 courses of chemotherapy, after the completion of chemotherapy, after surgery, and then every 6 months for 2 years.

Patients are followed every 2 months for 2 years and then every 3 months for 3 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 800 patients (200 per treatment arm) will be accrued for this study.