MULTICENTER, RANDOMIZED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF BEVACIZUMAB IN COMBINATION WITH ENDOCRINE TREATMENT COMPARED TO ENDOCRINE TREATMENT ALONE, IN POSTMENOPAUSAL WOMEN WITH ADVANCED OR METASTATIC CANCER WITH INDICATION OF HORMONOTHERAPY AS FIRST-LINE TREATMENT

INTERVENTION: Trade Name: Avastin Product Name: Bevacizumab Product Code: RO4876646 Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: Bevacizumab CAS Number: 216974‐75‐3 Other descriptive name: rhuMAb‐VEGF, anti‐VEGF, RO4876646 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 25‐ Trade Name: Femara Product Name: FEMARA Pharmaceutical Form: Tablet INN or Proposed INN: LETROZOLE CAS Number: 112809515 Trade Name: Faslodex Product Name: Faslodex Product Code: ZD9238 Pharmaceutical Form: Solution for injection CONDITION: Postmenopausal women with advanced or metastatic cancer with indication of hormonotherapy as first‐line treatment. ; MedDRA version: 14.0 Level: LLT Classification code 10006275 Term: Breast metastases System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) ; MedDRA version: 14.0 Level: LLT Classification code 10006212 Term: Breast carcinoma recurrent System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) PRIMARY OUTCOME: Main Objective: To compare the progression‐free survival (PFS) between both treatment arms. Primary end point(s): The patients will receive the study treatment until:; 1. The progression of the disease; 2. Occurrence of unacceptable toxicity; 3. Until the investigators decision to stop study treatment; 4. Until the patient refuses to continue the proposed treatment; Secondary Objective: To compare the following parameters between both treatment arms:; • Overall survival (OS); • Time to treatment failure (TTF); • Better response to treatment (RR); • Response duration (RD); • Clinical benefit proportion (CBP = CR + PR + SD > 6 months); • Safety and tolerance; INCLUSION CRITERIA: 1 Before starting the specific protocol procedures, the written informed consent must be obtained and documented. 2. Women = 18 years. 3. Capacity to comply with all the protocol requirements. 4. Functional ECOG status of 0 or 1. 5. Life expectancy = 24 weeks. 6. Postmenopausal women with histologically confirmed breast adenocarcinoma, with measurable or non‐measurable, locally advanced or metastatic (stage IV) disease. In the event that the patient only has locally advanced disease, she will not be able to undergo curative local treatment. Patients with metastasis confined to the bone can be chosen, but the disease must be confirmed by radiology, CT scan or NMR if there is any doubt after a single bone scan. 7. Patients with HER2‐negative disease evaluated by IHC and FISH/CISH (IHC 0 or 1+, or 2+ and negative FISH). Patients with 3+ by IHC cannot be chosen regardless of the FISH/CISH status and those with positive FISH/CISH (> 2 amplification