mTOR inhibitors in the management of hormone receptor-positive breast cancer: the latest evidence and future directions

There is an unmet therapeutic need in endocrine-resistant, hormone receptor (HR)-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (BC). Preclinical studies support the hypothesis that the mammalian target of rapamycin (mTOR) inhibition could potentially overcome resistance to endocrine therapy. A literature review regarding BC and mTOR inhibitors was undertaken. The reference lists from retrieved manuscripts were reviewed to identify further studies. Phase II studies have reported that the combination of mTOR inhibitors with endocrine therapy shows efficacy in patients with advanced disease that progressed after treatment with aromatase inhibitors. The recent findings of the phase III BOLERO-2 confirmed that everolimus in combination with exemestane significantly improved progression-free survival and response rate, with a manageable safety profile. The addition of everolimus to exemestane for women with HR-positive metastatic BC is now considered a new therapeutic strategy. However, a word of caution should be added regarding toxic effects, which might limit practical use and compliance. It is essential that clinicians are educated about key recommendations for toxicity management and specific guideline dose modifications. Additional research efforts with the addition of these compounds in the early-stage setting is greatly needed to improve the survival of patients with HR-positive BC.