Abstract
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.
Keywords
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Article info
Publication history
Published online: March 28, 2018
Accepted:
March 27,
2018
Received in revised form:
March 25,
2018
Received:
January 28,
2018
Identification
Copyright
© 2018 Elsevier B.V. All rights reserved.
