Trial Exploring Feasibility of Densification and Optimal Sequencing of Postoperative Adjuvant Fluorouracil, Epirubicin Plus Cyclophosphamide (FEC) and Docetaxel Chemotherapy in Patients With High Risk Primary Operable Breast Cancer

Inclusion Criteria:

• Histologically proven early breast cancer requiring adjuvant chemotherapy (lymph node positive or other features of high risk according to St-Gallen criteria)
• Margins of resection histologically free of invasive carcinoma and ductal carcinoma in situ.
• Radiotherapy performed according to center's policy and always follows completion of adjuvant chemotherapy
• Performance status 0 to 1 on the ECOG scale (Appendix A)
• The determination of ER and PgR is mandatory (immunohistochemical methods required; ER and/or PgR positivity is defined as > 1% of positive cells). Also determination of Her2neu is mandatory, either by immunohistochemistry or by FISH
• Age > 18 years and age <70 years (upper age limit based on the lack of safety data for this population).
• Normal cardiac function (assessment of LVEF by MUGA scan or echocardiography above the lower limit of normal for the institution).
• Adequate organ function (as defined by neutrophils > 1.5 x109/L, Platelets > 100 x 109/L, Hemoglobin > 10 g/dl, total bilirubin > 1 UNL, ASAT (SGOT) and ALAT (SGPT) > 1.5 UNL, alkaline phosphatase > 2.5 UNL, creatinine > 1.5 mg/dl (150 µmol/L)
• Complete staging work-up within 2 months prior to registration. All patients will have bilateral mammography, chest X-ray (PA and lateral) and/or CT-scan, abdominal ultrasound and/or CT scan, bone scan. In case of positive bone scan suspicious for metastases, bone X-ray (or bone CT-scan on spinal hot spots) is mandatory to rule out the possibility of metastatic disease. Other tests may be performed as clinically indicated.
• Negative pregnancy test (urine or serum) within 7 days prior to registration for all women of childbearing potential. Patients of childbearing potential must implement adequate non-hormonal measures to avoid pregnancy during study treatment (chemotherapy, radiotherapy and endocrine therapy). No pregnant or lactating patients are allowed.
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
• Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion criteria:

• Metastatic disease (M1) or inoperable residual axillary disease
• Prior systemic anticancer therapy for breast cancer (chemotherapy, hormone therapy of immunotherapy)
• Prior radiation therapy for breast cancer.
• Pre-existing motor or sensory neurotoxicity of a severity > grade 2 by NCI criteria.
• Pregnant or lactating patients
• Other serious illness or medical condition:
• Congestive heart failure or unstable angina pectoris, previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or high-risk uncontrolled arrhythmias.
• History of significant neurological or psychiatric disorders that would prohibit the understanding and giving of informed consent.
• Active uncontrolled infection
• Active peptic ulcer, unstable diabetes mellitus.
• Past or current history of other neoplasm except for curatively treated basal cell skin cancer or in situ carcinoma of the cervix.
• Chronic treatment with steroids unless initiated > 6 months prior to study entry and at low dose (< 20 mg methylprednisolone or equivalent)
• Concurrent treatment with hormonal replacement therapy: this treatment should be stopped at least 15 days before study entry.
• Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry