Persephone : Duration of Trastuzumab with Chemotherapy in patients with early breast cancer : Six months versus twelve

INTERVENTION: Product Name: Trastuzumab Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: recombinant humanised monoclonal antibody CAS Number: 180288‐69‐1 Other descriptive name: anti‐HER2 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 21mg/ml‐150 mg Trade Name: Herceptin (subcutaneous) Product Name: Trastuzumab Pharmaceutical Form: Solution for injection INN or Proposed INN: recombinant humanised monoclonal antibody CAS Number: 180288‐69‐1 Other descriptive name: anti‐HER2, Herceptin Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 120mg/ml‐ CONDITION: HER2 positive early breast cancer PRIMARY OUTCOME: Main Objective: Primary objective: A phase III, randomised trial comparing 6 months trastuzumab treatment with 12 months, in patients with Her 2 positive early breast cancer, in terms of disease‐free and overall survival.; ; Primary endpoint ; Disease‐free survival non‐inferiority (equivalence) of 6 months trastuzumab to 12 months in early breast cancer.; Primary end point(s): Primary end point; Disease‐free survival non‐inferiority (equivalence) of 6 months trastuzumab to 12 months in early breast cancer.; ; Secondary end point; •Overall survival non‐inferiority (equivalence) of 6 months trastuzumab to 12 months in early breast cancer.; •Health Economic Assessment (health resource use), toxicity and quality of life comparisons for 6 months and 12 months trastuzumab.; Secondary Objective: Secondary objectives (clinical); •Overall survival non‐inferiority (equivalence) of 6 months trastuzumab to 12 months in early breast cancer.; •Health Economic and quality of life superiority for 6 months trastuzumab versus 12 months.; •Cardiac function as assessed by left ventricular ejection fraction (LVEF) 3 monthly during trastuzumab therapy, and analysis of predictive factors for development of cardiac damage.; ; Secondary objectives (translational); •Assessment of tumour molecular profiling and candidate genes as prognostic and predictive markers of outcomes (disease‐free and overall survival).; •Assessment of patient genetic epidemiology and pharmacogenetics (single nucleotide polymorphism) as prognostic and predictive markers of outcomes (disease‐free and overall survival, and toxicity of trastuzumab).; ; ; INCLUSION CRITERIA: •Histological diagnosis of invasive breast cancer. •No evidence of metastatic disease. •Known hormone receptor status. •Overexpression of HER2 receptor. •Clear indication for neo‐adjuvant or adjuvant chemotherapy based on clinical and histopathological features. •Patient fit to receive neo‐adjuvant or adjuvant chemotherapy and trastuzumab in the opinion of the responsible physician. •No previous diagnosis of malignancy unless: ‐managed by surgical treatment only, and disease‐free for 10 years. ‐previous basal cell carcinoma, cervical carcinoma in situ or ductal carcinoma in situ of the breast. •Non‐pregnant and non‐lactating, with no intention of pregnancy during chemotherapy, and agrees to adopt adequate contraceptive measures if pre‐menopausal and sexually active. •No concomitant medical or psychiatric problems that might prevent completion of treatment or follow‐up. •Women or men 18 years or older. •Writte