José Baselga, MD, PhD, a professor in the Department of Medicine at Harvard Medical School and chief of Hematology/Oncology at Massachusetts General Hospital, discusses the clinical basis behind the success of the BOLERO-2 trial, which combined everolimus and exemestane in postmenopausal women with hormone receptor-positive breast cancer.

Baselga describes that data from multiple studies suggest that the mTOR pathway, which is downstream from PI3K and part of the PI3K/Akt/mTOR pathway, might play an important role in the formation of endocrine therapy resistance.

The mTOR pathway activates estrogen receptor (ER) transcription using the ribosomal protein S6. This type of activation can take place even in the ligand independent environment created by aromatase inhibitors (AIs). The ability to commence transcription without ligands results in AI resistance.

An initial neoadjuvant pilot study showed promising data suggesting that mTOR inhibition in combination with AIs could help stop resistance and proliferation. This information eventually led to the BOLERO-2 trial, which combined everolimus, an mTOR inhibitor, and exemestane, an AI.

Read more >>> Exemestane Plus Everolimus New Standard of Care for Postmenopausal Hormone Receptor-Positive Advanced Breast Cancer