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hormonoresistance in breast cancer
Saturday 27 May 2017
Endocrine therapy is the mainstay of treatment of estrogen-receptor-positive (ER+) breast cancer with an overall survival benefit. However, some adaptive mechanisms in the tumor emerge leading to the development of a resistance to this therapy.
Mechanisms of resistance to hormone therapy / hormonoresistance result in activation of transduction signal pathways, including the cell cycle regulation with cyclin D/CDK4/6/Rb pathway.
The strategy of combined hormone therapy with targeted agents has shown an improvement of progression-free survival (PFS) in several phase II or III trials, including three different classes of drugs: mTOR inhibitors, PI3K and CDK4/6 inhibitors.
A recent phase III trial has shown that fulvestrant combined with a CDK 4/6 inhibitor doubles PFS in aromatase inhibitor-pretreated postmenopausal ER+ breast cancer.
Other combinations are ongoing to disrupt the interaction between PI3K/AKT/mTOR and cyclin D/CDK4/6/Rb pathways.
Open references
Hormonoresistance in advanced breast cancer: a new revolution in endocrine therapy. Augereau P, Patsouris A, Bourbouloux E, Gourmelon C, Abadie Lacourtoisie S, Berton Rigaud D, Soulié P, Frenel JS, Campone M.
Ther Adv Med Oncol. 2017 May;9(5):335-346. doi : 10.1177/1758834017693195
PMID: 28529550 Free