Hormone therapy and breast cancer: emerging steroid receptor mechanisms

Abstract

Although hormone therapy is widely used by millions of women to relieve symptoms of menopause, it has been associated with several side-effects such as coronary heart disease, stroke and increased invasive breast cancer risk. These side-effects have caused many women to seek alternatives to conventional hormone therapy, including the controversial custom-compounded bioidentical hormone therapy suggested to not increase breast cancer risk. Historically estrogens and the estrogen receptor were considered the principal factors promoting breast cancer development and progression, however, a role for other members of the steroid receptor family in breast cancer pathogenesis is now evident, with emerging studies revealing an interplay between some steroid receptors. In this review, we discuss examples of hormone therapy used for the relief of menopausal symptoms, highlighting the distinction between conventional hormone therapy and custom-compounded bioidentical hormone therapy. Moreover, we highlight the fact that not all hormones have been evaluated for an association with increased breast cancer risk. We also summarize the current knowledge regarding the role of steroid receptors in mediating the carcinogenic effects of hormones used in menopausal hormone therapy, with special emphasis on the influence of the interplay or crosstalk between steroid receptors. Unraveling the intertwined nature of steroid hormone receptor signaling pathways in breast cancer biology is of utmost importance, considering that breast cancer is the most prevalent cancer among women worldwide. Moreover, understanding these mechanisms may reveal novel prevention or treatment options, and lead to the development of new hormone therapies that does not cause increased breast cancer risk.

Prognostic impact of tumor-specific insulin-like growth factor binding protein 7 (IGFBP7) levels in breast cancer: a prospective cohort study

“…MHT was weakly associated with lower serum levels of IGFBP7 in a subset of patients in the same cohort ( 35 ). The IGF/insulin and ER pathways, through which MHT mainly functions, are interconnected in breast cancer ( 13 , 36 ). A previous study based on the same breast cancer cohort reported that MHT was associated with lobular cancer and low histological grade ( 37 ).…”

Upregulation of an estrogen receptor-regulated gene by first generation progestins requires both the progesterone receptor and estrogen receptor alpha

“…Progestins often elicit biological effects that are distinct from each other and natural P 4 [reviewed in ( 2 , 44 , 45 )]. Indeed, it is known that some progestins have been linked to increased breast cancer risk, while oral micronized P 4 has not [reviewed in ( 14 , 17 )].…”

Update on hormone therapy for the management of postmenopausal women

“…Although taking CEE alone will not increase the incidence of breast cancer and HT will not increase the breast cancer mortality over time, HT should not be used for the sole purpose of reducing the risk of breast cancer risk because of complicated factors related to it (24,25). Estrogen-progestogen combinations are related to a higher risk of breast cancer compared to estrogenonly preparations, which indicates that the progestogen component is possibly the reason for the increased risk (90,91). The risk also increased with a longer duration of HT.…”