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In patients with HER2-negative metastatic breast cancer who are not candidates for endocrine therapy, several regimens are approved, but there is no consensus on which should be preferred. The impressive gains in progression-free survival achieved by combining two cytotoxic drugs or chemotherapy plus bevacizumab have not consistently translated into overall survival benefits. Survival in this population depends on a wide range of biological and clinical factors, some of which remain unclear. International guidelines recommend that combination regimens should be limited to clinically aggressive situations. However, an evidence-based definition that could help guide treatment decisions and trial design has not been established for so-called ‘poor-prognosis’ or ‘aggressive’ tumors. In this article, we summarize the current literature regarding prognosis and treatment of patients with no endocrine options for HER2-negative metastatic breast cancer. The choice of optimal systemic therapy should be based on robust prognostic factors, the biologic characteristics of the tumor, and the type and severity of comorbidities. Furthermore, we suggest that combination regimens (chemotherapy doublets or bevacizumab-based regimens) may be considered appropriate options for patients with well-defined criteria representing poor-prognosis disease.
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