A phase III study comparing anastrozole, letrozole and exemestane, upfront (for 5 years) or sequentially (for 3 years after 2 years of tamoxifen), as adjuvant treatment of postmenopausal patients with endocrine-responsive breast cancer

INTERVENTION: Trade Name: AROMASIN Pharmaceutical Form: Coated tablet INN or Proposed INN: Exemestane Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2.5‐ Trade Name: ARIMIDEX Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: Anastrozole Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 1‐ Trade Name: FEMARA Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: Letrozole Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2.5‐ Trade Name: TAMOXIFENE PHT*20CPR 20MG Pharmaceutical Form: Tablet INN or Proposed INN: Tamoxifen Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20‐ CONDITION: adjuvant hormono‐therapy in breast cancer patients ; MedDRA version: 6.1 Level: PT Classification code 10006279 PRIMARY OUTCOME: Main Objective: to compare the disease free survival (DFS) in patients treated with: ?sequential (tamoxifen 2 yrs AIs 3yrs) vs upfront (AIs 5yrs) strategy of treatment ?Anastrozole vs exemestane vs letrozole Primary end point(s): Disease‐free survival (DFS) defined as the time elapsed from randomization to the first among the following events: ?local or regional relapse ?distant metastasis ?contralateral breast cancer ?other invasive cancer different than breast ?death. Survival defined as time elapsing between the date of randomization and the date of death for any cause Safety: Clinical and laboratory toxicities will be graded according to NCI criteria CTCAE (Common Terminology Criteria for Adverse Events of National Cancer Institute v.3.0). The adverse events witch are not reported in NCI criteria will be graded as: mild (1), moderate (2), severe (3), and life threatening (4) Secondary Objective: To compare Distant‐metastasis‐free survival, cumulative incidence of contralateral breast cancer as first event, breast cancer‐free survival, overall survival, cumulative incidence and type of second non‐breast invasive cancer, toxicity INCLUSION CRITERIA: ‐Women with histological diagnosis of invasive breast cancer completely removed by surgery, any T, any N ‐Postmenopausal status ‐Primary tumor positive for ER or PgR (10% tumor cells positive by immunoistochemistry or  10 fmol/mg cytosol protein by ligand binding assay) ‐Patients with HER‐2 positive tumors are eligible provided that they receive trastuzumab according to registered schedule. ‐Signed informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range