Anthracycline-free Taxane Based Chemotherapy in Patients With HER2/Neu Negative Early Breast Cancer (planB)

Inclusion Criteria(Screening):

• Female patients, age at diagnosis 18 - 75 years
• Histological confirmed unilateral primary invasive carcinoma of the breast
• Adequate surgical treatment with complete resection of the tumor (R0) and resection of > or = 10 axillary nodes or SLN in clinically N0 patients
• T1 - T4 (if operable, inflammatory breast cancer is excluded)
• Her-2 non-over expressing tumor confirmed by IHC/FISH
• Estrogen and/or progesterone receptor analysis performed on the primary tumor prior to randomization. Results must be known at the time of randomization
• Node positive disease or node negative disease with at least one other risk factor (tumor size > or = 2 cm, grade > or = 2, ER and PR negative, high uPA//PAI-1 levels)
• No evidence for distant metastasis (M0) after conventional staging
• Performance Status ECOG < or = 1 or KI > or = 80 %
• The patient must be accessible for treatment and follow-up
• Written informed consent for central pathology review and evaluation of Recurrence Score (HR positive) and participation in the planB trial prior to beginning specific protocol procedures

HR positive patients:

• Patient willingness to participate in adjuvant chemotherapy planB trial if RS > 11
• Indication for chemotherapy given provided either > 4 involved lymph nodes or RS > 11 in 1-3 lymph nodes or N0 disease

Additional Inclusion Criteria (Randomisation to chemotherapy):

• Laboratory requirements (within 21 days prior to randomization):

  • Leucocytes > or = 3.5 109/L
  • platelets > or = 100 109/L
  • haemoglobin > or = 10 g/dL
  • total bilirubin < or = 1 ULN
  • ASAT (SGOT) and ALAT (SGPT) < or = 2.5 UNL
  • creatinine < 175 ymol/L (2 mg/dL)
• Negative pregnancy test (urine or serum) within 7 days prior to randomization in premenopausal patients
• LVEF within normal limits of each institution measured by echocardiography or MUGA scan and

Exclusion Criteria(Screening):

• HER2 over expression confirmed by IHC/FISH/CISH
• Known hypersensitivity reaction to the compounds or incorporated substances
• Known polyneuropathy > or = grade 2
• Severe and relevant comorbidity that would interact with the application of cytotoxic agents or the participation in the study including acute cystitis and ischuria and chronic kidney disease.
• Prior malignancy with a disease-free survival of < 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri or ipsilateral ductal carcinoma in-situ (DCISpTis of the breast)
• Non-operable breast cancer including inflammatory breast cancer
• Previous or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor
• Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry
• Male breast cancer
• Concurrent pregnancy; patients of childbearing potential must implement a highly effective (less then 1% failure rate) non-hormonal contraceptive measures during the study treatment
• Breast feeding woman
• Sequential breast cancer
• Lack of patient compliance

Additional Exclusion Criteria (Randomisation):

• Inadequate organ function including:

  • Leucocytes < 3,5 G/l
  • platelets < 100 G/l
  • creatinine or bilirubin above normal limits
  • alkaline phosphatise > 5 UNL
  • ASAT and/or ALAT associated with AP > 2.5 UNL
  • uncompensated cardiac function
• Time since axillary dissection > 42 days