Therapeutic Use of Estrogen Receptor β Agonists in Prevention and Treatment of Endocrine Therapy Resistant Breast Cancers: Observations From Preclinical Models

Abstract Breast cancer is one of the most common cancers in the world. The majority of breast cancers express estrogen receptor (ER)α, and endocrine therapy is the primary therapeutic approach to treat ER positive breast cancers. However, developing resistance and side effects are common events of these therapeutic strategies. Recent studies have evaluated the role of ERs sub types and demonstrated that ERα is a tumorigenic and ERβ functions as a tumor suppressor. In recent years, preclinical studies focused on the use of natural and synthetic ERβ agonists to treat wide varieties of cancers, including breast cancer. Successful studies conducted so far, have established that ERβ agonists are effective both alone and in combination with chemotherapeutic agents. These data have suggested that use of ERβ agonists in combination with endocrine therapy may be an effective treatment strategy in hormone receptor positive breast cancers. The present review focuses on the tumor suppressive role of ERβ, and the efficacy and mechanisms of several natural and synthetic ERβ agonists against breast cancer.