The Role of Mammalian Target of Rapamycin (mTOR) Inhibition in the Treatment of Advanced Breast Cancer

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Abstract
Endocrine therapy (ET) with aromatase inhibitors (AIs) has become the standard of care for postmenopausal women with hormone-receptor-positive (HR(+)) advanced breast cancer (ABC); however, progression following initial treatment remains a major clinical challenge given the large patient population, many of whom develop progressive disease. There is an unmet need for treatment strategies that can overcome endocrine resistance. Growth factor-mediated signaling pathways, such as the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway, contribute to estrogen-independent growth that may lead to endocrine resistance. Preclinical studies have demonstrated that the use of mTOR inhibitors, such as everolimus and temsirolimus, is a promising strategy to potentially enhance endocrine sensitivity in ABC. This review will focus on the current ET options for women with HR(+) ABC who have progressed on prior AI therapy, the role of mTOR-mediated signaling in breast cancer, and the clinical evidence supporting the use of mTOR inhibitors.

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