Patient case: 56-year-old female with breast cancer; genetic feature: ERBB2

Clinical trial: 6xFU/Epirubicin/Cyclophosphamide (FEC) Compared to 3xFEC-3xDocetaxel in High-risk Node-negative Breast Cancer Patients

Summary: In low-risk node-negative breast cancer patients adjuvant chemotherapy should be spared. The identification of this subgroup can be based either on clinical and pathological or on tumour-biological criteria. Due to their high prognostic impact, the tumour-biological invasion markers uPA/PAI-1 (urokinase-type plasminogen activator and its inhibitor PAI-1) are potential candidates to effectively assess the risk of relapse in node-negative breast cancer. This study is aimed to compare the risk assessment by the traditional clinico-pathological factors and by tumour-biological factors. The second study question refers to the comparison between an adjuvant combination treatment with FE100C*6 and a sequential treatment with FE100C*3 and Docetaxel*3.

Detailed description: 1. To compare FEC*6 with FEC*3 followed by DOC*3 with regard to:
  -  the primary endpoint of the study: Disease-Free Survival (DFS)
  -  the secondary endpoints: Overall Survival (OS), compliance, and toxicity of chemotherapy in each patient group
  2. To compare patients with low risk according to clinico-pathological versus those according to biological risk criteria with regard to:
  -  the proportion of low risk versus high risk patients
  -  DFS
  -  OS (secondary endpoint)

Eligibility: Inclusion Criteria:
  -  Histological proven primary breast cancer
  -  Tumour size >0.5 cm and <5 cm (pT1b-pT2, pN0, M0)
  -  Axillary lymph nodes tumour free (node-negative disease)
  -  Adequate surgical procedure: R0-resection and axillary dissection with more than 10 lymph nodes examined or adequate sentinel procedure in a qualified centre
  -  Frozen tumour tissue available (for analysis of biological markers and microarrays, centres with biological risk assessment only). The material has to be stored in liquid nitrogen immediately after excision.
  -  Paraffin blocks or (at least) pathology slides of primary tumour (stained and unstained) and axillary nodes (stained) available for central review.
  -  HER-2/neu determination by immunohistochemistry. Patients will be stratified to be HER-2/neu-negative or HER-2/neu-positive (HER-2/neu Score 3+, or HER-2/neu Score 2+ and FISH positive).
  -  No distant metastasis
  -  Age >18 years, <70 years
  -  Performance status ECOG <2 (WHO Performance Status 0-1)
  -  Adequate cardiac function (echocardiographically measured left ventricular ejection fraction (LVEF) or shortening fraction (SF) within the normal limits, i.e. ≥55%)
  -  Adequate bone function (neutrophil count >1.5 x109 /l and platelet count >100 x109 /l)
  -  Adequate renal function (serum creatinine <120 µmol/l or 1.35 mg/dl) and hepatic function (serum bilirubin <1 x UNL, ASAT or ALAT (SGOT or SGPT) <2,5 x UNL)
  -  Before patient registration/randomization, written informed consent must be obtained according to ICH/EU GCP, and national/local regulations
  Exclusion Criteria:
  -  Chemotherapy contraindicated
  -  Inflammatory breast cancer, tumour infiltrated axillary lymph nodes including the sentinel node.
  -  Other concomitant pathology compromising survival (at entry), or preventing the administration of chemotherapy with either FEC or Docetaxel
  -  Other serious illness or medical condition that may interfere with the understanding and giving of informed consent and the conduct of the study
  -  Estimated life-expectancy <10 years (irrespective of breast cancer diagnosis)
  -  Patient not accessible for treatment and follow up
  -  Endocrine treatment not according to the latest standard recommendations of the AGO Kommission "Mamma"
  -  Pregnancy, lactation (sufficient non-hormonal contraception in fertile women required)
  -  Surgery more than six weeks ago at the start of chemotherapy
  -  Pre-existing polyneuropathy
  -  Previous or concomitant other malignancy (including contralateral breast cancer) except adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix
  -  Prior chemotherapy or radiotherapy or endocrine therapy

Relevance to patient case: definitely relevant