Protective Effects of Human Chorionic Gonadotropin Against Breast Cancer: How Can We Use This Information to Prevent/Treat the Disease?

Breast cancers (BCs) are the most common malignancies among women worldwide. Giving birth to a first child before 24 years of age decreases the BC risk by about half, when women reach menopausal years. The scientific evidence suggests that the actions of human chorionic gonadotropin (hCG) are responsible for this decrease. Human BC cells and tissues contain hCG/luteinizing hormone receptors. The activation of the receptors results in an increase in cell differentiation and apoptosis. Conversely, it decreases the cell proliferation, invasion, and survival. The hCG actions are primarily cyclic adenosine monophosphate/protein kinase A mediated, require the presence of receptors, and involve blocking the activation and nuclear translocation of the transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The women with a higher hCG levels during pregnancy tend to have a lower BC incidence and those with the receptor-positive tumors have a longer metastasis-free survival. The long-term benefits of pregnancy/hCG seem to come from permanent signature genomic imprinting and expression changes, which are characterized by low cell proliferation, increased efficiency of DNA repair mechanisms, cell differentiation, and cells resistance to carcinogenesis. These findings could provide clinical opportunities to use hCG for the prevention of BC in this modern era of increasing number of young women in our societies waiting longer than ever to have their first child. In addition, hCG may be useful to reduce and/or eliminate cellular targets of carcinogenic changes during an active ongoing disease.