The role of mammalian target of rapamycin (mTOR) inhibition in the treatment of advanced breast cancer.

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.