The action of estrogens and progestogens in the young female breast

Evidence from different sources sustains a pro-oncogenic role of hormones, estrogens and progestogens, on the breast. The issue is of interest for young women, who are exposed to the hormonal changes imposed by the ovarian cycle and, often, take hormones with contraceptive purposes. Experimental and clinical studies show that both estrogens and progesterone are involved in mammary development during puberty and lactation, the changes being observed across mammalian species, including humans. Estrogen receptors, and more particularly the alpha isoform, participate in molecular processes of stem cells differentiation and epithelial proliferation through paracrine actions implicating growth factors. Progesterone also contributes through paracrine mechanisms involving one member of the tumor necrosis factor (TNF) family, the receptor activator of nuclear factor κB ligand (RANKL) and its receptor (RANK). Epidemiological studies have found that the length of the exposure to endogenous hormones, as determined by an early menarche or a late menopause, is a risk factor for breast cancer. Additional evidence has derived from studies with compounds modulating the estrogen or the progesterone receptors. Selective estrogen receptor modulators (SERM), like tamoxifen, have been shown to decrease the risk of breast cancer in both pre- and post-menopausal women. Aromatase inhibitors, which drastically reduce the levels of circulating estrogens, have reproduced the findings. The selective progesterone receptor modulators (SPRM) have been less investigated and issues concerning safety have arisen. These observations have interest for young women. High-risk women may consider the use of SERMs, for example, to reduce their risk. Much more common is the case of women who take hormones for contraception. The goal of the present article is twofold: i) to summarize the actual knowledge of the mechanisms implicating estrogens and progestogens on the risk for breast cancer and ii) to provide rationality for the debate about potential cancer risk of hormonal contraceptives, frequently used by premenopausal women.