Androgens and the breast

Constantine Dimitrakakis,Carolyn Bondy

doi:10.1186/bcr2413

Abstract

Androgens have important physiological effects in women while at the same time they may be implicated in breast cancer pathologies. However, data on the effects of androgens on mammary epithelial proliferation and/or breast cancer incidence are not in full agreement. We performed a literature review evaluating current clinical, genetic and epidemiological data regarding the role of androgens in mammary growth and neoplasia. Epidemiological studies appear to have significant methodological limitations and thus provide inconclusive results. The study of molecular defects involving androgenic pathways in breast cancer is still in its infancy. Clinical and nonhuman primate studies suggest that androgens inhibit mammary epithelial proliferation and breast growth while conventional estrogen treatment suppresses endogenous androgens. Abundant clinical evidence suggests that androgens normally inhibit mammary epithelial proliferation and breast growth. Suppression of androgens using conventional estrogen treatment may thus enhance estrogenic breast stimulation and possibly breast cancer risk. Addition of testosterone to the usual hormone therapy regimen may diminish the estrogen/progestin increase in breast cancer risk but the impact of this combined use on mammary gland homeostasis still needs evaluation.

Highlights

Treatment of women with physiological testosterone supplementation to remedy hypoactive sexual desire disorder is an area of great interest at present [1]
Experimental data suggest that conventional estrogen treatment regimens, both as oral contraceptives (OCs) and hormone therapy (HT) [3], upset the normal estrogen/ androgen balance and promote ‘unopposed’ estrogenic stimulation of mammary epithelial proliferation and, potentially breast cancer risk
Breast cancer patients (n = 194) with high testosterone had significantly lower event-free survival than those with low testosterone (P = 0.004) and a significantly higher risk of breast cancer events with an adjusted hazard ratio of 1.77

Summary

Introduction

Treatment of women with physiological testosterone supplementation to remedy hypoactive sexual desire disorder is an area of great interest at present [1]. None of these studies manage, to disconnect the risk associated with increased estradiol levels from the androgen component, and since androgens are the obligate precursors for estradiol synthesis, this is a major confounding factor in assessing the role of androgen independently of the known cancer-promoting estrogen effect In line with these observations, a recent study [35] concluded that increased breast cancer risk with increasing body mass index among postmenopausal women is largely the result of the associated increase in estrogens. Epidemiological studies on the association between androgens and breast cancer risk

Conclusion

Schover LR

Lobo RA

Findings

Labrie F