IBCSG 15-95 - Randomised trial of high-dose epirubicin and cyclophosphamide x 3 supported by peripheral blood progenitor cells versus anthracycline and cyclophosphamide x 4 followed by cyclophosphamide, methotrexate, and 5-fluoruracil x 3 as adjuvant treatment for high risk operable stage II and stage III breast cancer in premenopausal and young postmenopausal (<=65 yrs) patients

INTERVENTION: Arm B: Filgrastim (10ug/kg subcutaneously daily) for 6 days with leukapheresis on days 5‐7. This is followed by 3 cycles (cycle =21 days) Epirubicin (200mg/m^2 iv over 12 hours on day 1), cyclophosphamide (4gm/m^2 iv as 4 divided doses – day 2), MESNA (7.2gm/m^2 – days 2 & 3), Peripheral Blood Progenitor Cell (PBPC) infusion (day 5) and Filgrastim (5ug/kg daily subcutaneously – from day 6 until White Blood Cells>10 x 10^9/l). Tamoxifen (20mg orally daily) then follows for 5 years. CONDITION: Breast Cancer PRIMARY OUTCOME: Duration quality‐adjusted time without symptoms and toxicity (TWiST and Q‐TWiST) Overall survival SECONDARY OUTCOME: Toxicity Cost‐effectiveness Disease‐free survival and Systemic disease‐free survival duration. Quality of life INCLUSION CRITERIA: • Histologically proven breast cancer• Primary tumour must be classified as T1a,b,c, T2 or T3, N1 or N2, M0• Patients must be categorized as at least one of the following:a) >/= 10 involved axillary nodesb) >/= 5 involved axillary nodes and primary tumour that is ER‐negativec) >/= 5 involved axillary nodes and T3 tumour who had breast cancer surgical procedure (irrespective of ER status)• Attempts should be made to determine estrogen receptor status of tumour• Patients must have had:a) Either total mastectomy or breast‐conserving procedure (lumpectomy or quadrantectomy) for T1, T2 or T3 tumours.b) Primary breast cancer surgical procedure must be within six weeks prior to randomization• Tumour must be confined to breast and axillary lymph nodes. All nodes must be examined by pathologist• Left ventricular ejection fraction greater than 50% by resting MUGA radionuclide scan• Adequate marrow function (WBC >/= 4.0 x 10^9/l and platelet count >/= 100 x 10^9/l)• Adequate r