Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer

SUMMARY: The mechanism of resistance to hormonal therapy in breast cancer is thought to be related to the activation of mTOR pathway, independent of ER (estrogen receptor) signalling pathway. To test this hypothesis, the authors in this study (BOLERO-2) decided to combine mTOR inhibition with estrogen deprivation. In a phase III trial, patients with ER positive, advanced breast cancer, who had recurred or progressed on prior therapy with nonsteroidal aromatase inhibitors (anastrozole or letrazole), were randomized in a 2:1 ratio to either receive everolimus (mTOR inhibitor) and exemestane (steroidal aromatase inhibitor) or exemestane and placebo. The primary end point of Progression Free Survival was significant with 10.6 months for mTOR inhibitor plus exemestane vs 4.1 months for exemestane plus placebo, according to central review (hazard ratio, 0.36; P<0.001). This new paradigm of adding everolimus to hormonal therapy should change the way we manage patients with advanced breast cancer, who are resistant to hormonal therapy alone. Baselga J, Campone M, Piccart M, et al. N Engl J Med 2012; 366:520-529