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

Research output: Contribution to journalReview articlepeer-review

61 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)25-42
Number of pages18
JournalJournal of mammary gland biology and neoplasia
Issue number1
StatePublished - Mar 2013
Externally publishedYes

Bibliographical note

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


  • Epigenetics
  • Hormone therapy
  • In utero
  • Oral contraceptives
  • Pregnancy
  • Synthetic estrogens


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