Exposures to Synthetic Estrogens at Different Times During the Life, and Their Effect on Breast Cancer Risk

  • Leena Hilakivi-Clarke
  • Sonia de Assis
  • Anni Warri


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.


Synthetic estrogens Pregnancy In utero Oral contraceptives Hormone therapy Epigenetics 



breast imaging reporting and data system


bone morphogenic protein 4


clear cell adenocarcinoma


conjugated equine estrogens






DNA methyltransferase


17-β estradiol


ethinyl estradiol


european prospective investigation into cancer and nutrition


estrogen receptor α


estrogen receptor β


enhancer of zeste-2


fibroblast growth factors


high fat


histone deacetylase


hormone therapy


human embryonic stem cells


insulin-like growth factor




national surgical adjuvant breast and bowel project


medroxyprogesterone acetate




oral contraceptives


parathyroid hormone-related protein


parathyroid hormone 1 receptor


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



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

Funding support

This study was supported by the National Cancer Institute (R01 CA164384-01A1, U54 CA100970, U54CA149147, and P30 CA051668)


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Leena Hilakivi-Clarke
    • 1
    • 3
  • Sonia de Assis
    • 1
  • Anni Warri
    • 1
    • 2
  1. 1.Department of OncologyGeorgetown UniversityWashingtonUSA
  2. 2.Institute of BiomedicineUniversity of Turku Medical FacultyTurkuFinland
  3. 3.Georgetown University Medical CenterWashingtonUSA

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