Lactogens and estrogens in breast cancer chemoresistance

Abstract

Tumor resistance to chemotherapy in advanced breast cancer is a major impediment to treatment success. Resistance can be induced by the drugs themselves or result from the action of internal factors. The role of hormones in chemoresistance has received little attention. This article focuses on two classes of hormones: lactogens and estrogens. Lactogens include prolactin, growth hormone and placental lactogen, all of which can activate the prolactin receptor. Estrogens include endogenous steroids and nonsteroidal compounds from the environment termed endocrine disruptors, all of which can activate ‘classical’ estrogen receptors (ERα and ERβ), as well as other types of receptors. Both lactogens and estrogens antagonize cytotoxicity of multiple chemotherapeutic agents through complementary mechanisms. The implications of chemoresistance by these hormones to patients with breast cancer, and the potential benefits of developing combinatorial anti-lactogen/anti-estrogen treatment regimens, are discussed.

Keywords::

• bisphenol A
• breast cancer
• chemoresistance
• cisplatin
• endocrine disruptors
• endogenous estrogens
• growth hormone
• placental lactogen
• prolactin
• prolactin receptor

Financial & competing interests disclosure

This work was supported by NIH grants ES012212 and CA096613, DOD BC05725, Susan G Komen BCRT87406, and a grant from the Elsa U Pardee foundation (to Nira Ben-Jonathan), and the NIH Center for Environmental Genetics P30 ES06096 (to Eric M Jacobson). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.