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Updated: Jun 29, 2026
10:36
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Endogenous estrogens as carcinogens through metabolic activation
1Department of Environmental Health Sciences, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205, USA. jyager@jhsph.edu
Journal of the National Cancer Institute. Monographs
|August 30, 2000
Summary
Excessive estrogen exposure increases breast cancer risk by promoting cell proliferation and DNA damage through its oxidative metabolites, catechol estrogens. Genetic factors influencing estrogen metabolism may further modify this risk.
Area of Science:
- Endocrinology
- Molecular Biology
- Cancer Research
Background:
- Estrogen exposure is a known risk factor for breast cancer.
- The standard model implicates estrogen-induced cell proliferation and DNA synthesis errors.
- Emerging evidence suggests a role for estrogen's oxidative metabolites in carcinogenesis.
Purpose of the Study:
- To review evidence supporting the role of oxidative estrogen metabolites in estrogen carcinogenesis.
- To present a paradigm for how estrogens contribute to human breast cancer development.
- To discuss the implications of genetic and environmental factors on estrogen metabolism and cancer risk.
Main Methods:
- Review of cell culture and whole animal experimental studies.
- Analysis of molecular epidemiologic studies on genetic polymorphisms.
- Discussion of mechanisms involving estrogen metabolites, DNA adducts, and oxidative stress.
Main Results:
- Catechol estrogens act as signaling molecules and can form DNA adducts.
- Oxidative metabolites generate reactive oxygen species, causing DNA damage.
- Estrogens and their metabolites demonstrate carcinogenicity in animal models.
- Polymorphisms in catechol-O-methyltransferase (COMT) are linked to altered breast cancer risk, though inconsistently.
Conclusions:
- Oxidative metabolites of estrogen, particularly catechol estrogens, play a significant role in estrogen carcinogenesis.
- Genetic polymorphisms and environmental factors influencing estrogen metabolism are critical in determining individual breast cancer risk.
- Further mechanistic and molecular epidemiologic studies are needed to identify these factors and their precise impact on human cancer risk.
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