Pharmacotherapy
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The mammalian target of rapamycin (mTOR) is a signaling kinase of the phosphatidylinositol 3-kinase/protein kinase B (also known as Akt) signaling pathway that mediates cell growth and metabolism. Dysregulation of the mTOR pathway creates a favorable environment for the development and progression of many cancers, including breast cancer, and is associated with the development of resistance to endocrine therapy and to the anti-human epidermal growth factor receptor-2 (HER2) monoclonal antibody trastuzumab. Therefore, the addition of mTOR inhibitors to conventional breast cancer therapy has the potential to enhance therapeutic efficacy and/or overcome innate or acquired resistance. ⋯ Everolimus is generally well tolerated; hematologic abnormalities and stomatitis are most common adverse events when this drug is combined with cytotoxic chemotherapy. Based on these promising results, everolimus is currently under evaluation in a series of phase III Breast Cancer Trials of Oral Everolimus (BOLERO) trials of women with HER2-positive and estrogen receptor-positive breast cancer. Results of these trials will help to establish the role of everolimus in the treatment of clinically important breast cancer subtypes.