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Strategies to overcome endocrine therapy resistance in hormone receptor-positive advanced breast cancer

Rowan T Chlebowski

Use of endocrine therapies has made hormone receptor-positive breast cancer a manageable disease if diagnosed at an early stage. However, endocrine therapy resistance is a persistent problem in patients with advanced breast cancer. Ongoing research has identified a number of mechanisms that may mediate resistance, including estrogenindependent activation of the estrogen receptor; increased signaling through the RAS/MAPK, NF-kB, or PI3K/Akt/mTOR pathway; and maintenance of cyclin D1 expression. Based on such findings, various strategies to overcome endocrine resistance have been developed. Although some therapies are in early development, others are available in the clinic. The novel treatment strategies under evaluation in clinical trials for managing patients with endocrine-resistant advanced breast cancer will be reviewed in combination with endocrine therapy.