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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, SouliĆ© P, Frenel JS, Campone M.
Ther Adv Med Oncol. 2017 May;9(5):335-346. doi : 10.1177/1758834017693195
PMID: 28529550 Free