OBJECTIVES:
Primary
* Compare the pathologic complete response rates in women with stage I-III primary breast cancer treated with neoadjuvant epirubicin hydrochloride, cyclophosphamide, and docetaxel with versus without capecitabine followed by surgery .
* Compare the pathologic complete response rates in women with HER-2/neu-positive tumors receiving trastuzumab (Herceptin®) simultaneously with neoadjuvant epirubicin hydrochloride, cyclophosphamide, and docetaxel to women with HER-2/neu-negative tumors receiving neoadjuvant chemotherapy only.
Secondary
* Determine the toxicity of these regimens in these patients.
* Determine the disease-free (loco-regional and distant) survival and overall survival of patients treated with these regimens.
* Determine the disease-free (loco-regional and distant) survival and overall survival of patients treated with or without trastuzumab.
* Determine the breast conservation rate in patients treated with these regimens.
* Determine the frequency of the use of sentinel node biopsy for selecting patients for neoadjuvant chemotherapy.
* Compare the frequency of sentinel node biopsies at surgery after neoadjuvant chemotherapy in each arm.
* Determine the pathologic complete response rates to each regimen in the subgroup of patients with locally advanced (T4a-d, N0-3, M0) breast cancer.
* Determine the response rate (complete response, partial response, or no change) at surgery (by imaging methods and by histopathological exam) in patient subgroups according to their response after four treatments with epirubicin hydrochloride and cyclophosphamide.
* Determine the intention for the use of neoadjuvant chemotherapy, in terms of freedom from disease, avoiding mastectomy, improving breast conservation, and gaining information about efficacy.
OUTLINE: This is a randomized, controlled, open-label, multicenter study. Patients are stratified according to participating site, clinical response after 4 courses of epirubicin hydrochloride and cyclophosphamide (complete response vs partial response vs no change), HER-2/neu-status (negative vs 3+ by immunohistochemistry \[IHC\] or positive by fluorescence in situ hybridization \[FISH\]), estrogen receptor (ER)/progesterone receptor (PR) status (ER or PR positive vs ER and PR negative), and extent of disease (T4 or N3 vs T1-3 and N0-2).
All patients receive epirubicin hydrochloride IV over 30-60 minutes and cyclophosphamide IV over 60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients are then randomized to 1 of 3 treatment arms.
* Arm I: Patients receive docetaxel IV over 60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive docetaxel as in arm I. Patients also receive oral capecitabine twice daily on days 1-14. Treatment with docetaxel and capecitabine repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
* Arm III: Patients receive docetaxel as in arm I. Patients then receive oral capecitabine twice daily on days 1-14. Treatment with capecitabine repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients with HER-2/neu-positive tumors also receive trastuzumab (Herceptin®) IV over 90 minutes on day 1 of each course of chemotherapy (during treatment with epirubicin hydrochloride and cyclophosphamide AND during randomized treatment).
Within 2 weeks after completion of chemotherapy, all patients undergo surgery. Within 2 weeks after surgery, patients with HER-2/neu-positive tumors resume trastuzumab treatment for up to 1 year.
After completion of study treatment, patients are followed periodically for at least 5 years.
PROJECTED ACCRUAL: A total of 1,500 patients will be accrued for this study.
