Bevacizumab + Endocrine Treatment vs Endocrine Treatment as First Line in Postmenopausal Women

Inclusion Criteria

• Before starting the specific protocol procedures, the written informed consent must be obtained and documented.
• Women ≥ 18 years.
• Capacity to comply with all the protocol requirements.
• Functional Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
• Life expectancy ≥ 24 weeks.
• 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 Nuclear magnetic resonance (NMR) if there is any doubt after a single bone scan.
• Patients with HER2-negative disease evaluated by Immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH)/Chromogenic in situ hybridisation (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 amplifications) cannot be chosen either, regardless of the IHC findings.
• Positive hormone receptors (estrogen receptor [ER] and/or progesterone receptor [PgR]) evaluated by a local or central laboratory, according to the criteria of the participating institution.
• Patients who are candidates for receiving first-line treatment with letrozole.
• Patients may have received (neo)adjuvant chemotherapy, provided that the last dose of the latter was received at least 12 months before randomization. Patients must be recovered from toxicity.
• The patients are allowed to have received adjuvant radiotherapy, provided that it was completed at least 6 weeks before randomization and the patient has recovered from the reversible acute effects of the radiation. The previous administration of radiotherapy to palliate the pain of bone metastases is authorized, provided that:
• Not more than 30% of bone marrow has been irradiated.
• The patient has recovered from the reversible acute effects of the radiation.
• The patient has at least one metastatic location which has not been irradiated and which may be evaluated for progression, or a clear progression of the bone disease has been objectified after the end of the palliative radiotherapy.
• The patients may have received any kind of previous (neo)adjuvant hormone therapy provided that they are considered to be candidates for first-line hormonotherapy with either letrozole or fulvestrant.
• The treatment with bisphosphonates is allowed and recommended for patients with bone metastases. Whenever it is possible, the treatment should be started before or within the 4 weeks of starting the study therapy. The patients starting treatment with bisphosphonates must be carefully evaluated so that they do not mask the progression of the disease.
• In the patients with heart failure risk (e.g. previously treated with > 360mg/m2 of doxorubicin or equivalent doses of other anthracyclines), the Left Ventricular Ejection Fraction (LVEF) must be determined by means of an echocardiogram or radionuclide ventriculography (MUGA), and it must t be > the lower limit of normal.

Exclusion Criteria

• Evolutionary disease requiring an immediate treatment with cytotoxic chemotherapy according to the investigator's judgment.
• Patients with locally advanced breast cancer who are expected to undergo surgery or curative radiotherapy.
• Previous chemotherapy or hormonotherapy for the metastatic disease. Patients may have received neoadjuvant chemotherapy or neoadjuvant hormonotherapy with curative intention as a part or as an alternative to an adjuvant treatment. For the previous neoadjuvant hormonotherapy the same premises than for the adjuvant hormonotherapy are valid.
• Previous therapy with anti-vascular endothelial growth factor (VEGF) or VEGF Receptor (VEGFR) tyrosine-kinase inhibitors.
• History of another patholo