Women are using estrogens for many purposes, such as to prevent pregnancy or miscarriage, or to treat menopausal symptoms. Estrogens also have been used to treat breast cancer which seems puzzling, since there is convincing evidence to support a link between high lifetime estrogen exposure and increased breast cancer risk. In this review, we discuss the findings that maternal exposure to the synthetic estrogen diethylstilbestrol during pregnancy increases breast cancer risk in both exposed mothers and their daughters. In addition, we review data regarding the use of estrogens in oral contraceptives and as postmenopausal hormone therapy and discuss the opposing effects on breast cancer risk based upon timing of exposure. We place particular emphasis on studies investigating how maternal estrogenic exposures during pregnancy increase breast cancer risk among daughters. New data suggest that these exposures induce epigenetic modifications in the mammary gland and germ cells, thereby causing an inheritable increase in breast cancer risk for multiple generations.
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breast imaging reporting and data system
bone morphogenic protein 4
clear cell adenocarcinoma
- CEE :
conjugated equine estrogens
european prospective investigation into cancer and nutrition
- ERα :
estrogen receptor α
estrogen receptor β
enhancer of zeste-2
fibroblast growth factors
human embryonic stem cells
insulin-like growth factor
national surgical adjuvant breast and bowel project
parathyroid hormone-related protein
parathyroid hormone 1 receptor
- PcTG :
polycomb target genes
random periareolar fine-needle aspiration
study of tamoxifen and raloxifene
terminal ductal lobular unit
terminal end buds
tumor suppressor gene
women’s health initiative
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L. Hilakivi-Clarke has served as an expert witness in a case concerning breast cancer risk in daughters of DES-exposed mothers on behalf of the plaintiffs
This study was supported by the National Cancer Institute (R01 CA164384-01A1, U54 CA100970, U54CA149147, and P30 CA051668)
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Hilakivi-Clarke, L., de Assis, S. & Warri, A. Exposures to Synthetic Estrogens at Different Times During the Life, and Their Effect on Breast Cancer Risk. J Mammary Gland Biol Neoplasia 18, 25–42 (2013). https://doi.org/10.1007/s10911-013-9274-8
- Synthetic estrogens
- In utero
- Oral contraceptives
- Hormone therapy