Onkológia 2/2021

Treatment of HR+, HER2- advanced/metastatic breast cancer according to ESO-ESMO recommendations ABC 5

Advanced breast cancer (ABC) include inoperable locally advanced breast cancer (LABC) and metastatic breast cancer (MBC) which is disseminating mainly to bones, lungs and liver. More than two thirds of breast cancers express estrogen receptors (ER) and progesterone receptors (PR) while not expressing the human epithelial growth factor receptor 2 (HER-2). In this molecular subtype, endocrine therapy is preferred treatment choice. Despite having several treatment options ABC has been considered incurable with median survival 2-3 years. Recently, in pursuit of delaying or bridging the endocrine resistance responsible for disease progression, several types of targeted therapies have been established in clinical practice: the mammalian target inhibitor rapamycin mTOR – everolimus, selective inhibitors of cyclin- dependent kinases 4 and 6 (CDK4/ 6) – palbociclib, ribociclib and abemaciclib, and the phosphatidylinositol 3- kinase (PI3K) inhibitor – alpesilib. To date, randomized clinical trials have shown the most significant benefit of a combination of endocrine therapy (aromatase inhibitors or fulvestrant) and selective CDK4/ 6 inhibitors in HR +, HER-2 - ABC patients, in first and second line of treatment, except in cases of life- threatening rapidly progressing disease or visceral crisis. Optimal timing and sequence of targeted therapies as well as selection of particular molecule, are yet to be answered.

Keywords: advanced breast cancer, endocrine therapy, systemic therapy, CDK4/6 inhibitors, ABC 5