Onkológia 1/2015

Dual inhibition after failure of NSAI as a solution to hormone therapy resistance

Breast cancer is the most common cancer among women worldwide. Approximately 70 – 75 % of breast cancers exhibits hormone receptor positivity. Endocrine therapy plays an important role, therefore, the development of endocrine resistance is a immense problem. Effective treatments for hormone-receptor-positive (HR+) breast cancer following relapse or progression on nonsteroidal aromatase inhibitor (NSAI) therapy are urgently needed. Preclinical and clinical evidence shows that rapamycin derivative everolimus (EVE), has direct anticancer effects. Moreover, mTOR inhibition can enhance the efficacy of endocrine therapy in breast tumors. The strategy of dual inhibition with endocrine therapy and an mTOR inhibitor was investigated in the BOLERO-2 trial. Data from this trial demonstrated that everolimus and exemestane significantly prolonged progression-free survival (PFS) versus placebo plus exemestane alone. A relatively new class of drugs are inhibitors of PI3K, they allow to affect the endocrine resistance by interference with signaling cascade PI3K. The first results of the blinded randomized clinical study evaluating the role of PI3K inhibitor in patients with breast cancer were presented at SABCS 2014.

Keywords: breast cancer, endocrine resistance, non-steroidal aromatase inhibitors (NSAIs), mTOR inhibitor everolimus.