Estrogen carcinogenesis in breast cancer.

  title={Estrogen carcinogenesis in breast cancer.},
  author={James D. Yager and Nancy E Davidson},
  journal={The New England journal of medicine},
  volume={354 3},
  • J. YagerN. Davidson
  • Published 19 January 2006
  • Medicine, Biology
  • The New England journal of medicine
n this article, we review recent findings related to estrogen exposure and the risk of breast cancer, the mechanisms that may be involved, and the clinical implications of these findings. The weight of evidence indicates that exposure to estrogen is an important determinant of the risk of breast cancer. The mechanisms of carcinogenesis in the breast caused by estrogen include the metabolism of estrogen to genotoxic, mutagenic metabolites and the stimulation of tissue growth. Together, these… 

Figures and Tables from this paper

Estrogen carcinogenesis in breast cancer.

  • D. Germain
  • Biology, Medicine
    Endocrinology and metabolism clinics of North America
  • 2011

Mechanistic Effects of Estrogens on Breast Cancer

This article reviews studies that address estrogen-mediated breast cancer development, the prevalence of occult tumors at autopsy, and the natural history of breast cancer as predicted by a newly developed tumor kinetic model.

Current research on breast carcinogenesis

Insight into the mechanisms of the causation of cancer by estrogen will be identifed determinants of susceptibility to breast cancer and new targets for prevention and therapeutic intervention.

The role of estrogen receptor in melanoma

The potential role of ER as a surrogate marker for predicting melanoma progression, response to therapy, and patient survival is investigated and its potential role in carcinogenesis and progression of cutaneous melanoma is reviewed.

Estrogens and breast cancer: Mechanisms involved in obesity-related development, growth and progression

Hormone-Responsive Cancers

Dissecting the prevention of estrogen-dependent breast carcinogenesis through Nrf2-dependent and independent mechanisms

The use of specific phytochemicals and dietary supplements can inhibit the risk of breast cancer not only by the modulation of several estrogen-activating enzymes but also through the induction of various cytoprotective enzymes that reestablish the homeostatic balance of estrogen metabolism via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent and independent mechanisms.

Genomic-Epidemiologic Evidence That Estrogens Promote Breast Cancer Development

It is argued that the fraction of driver genes regulated by E2-ESR1 is lower in malignancies not associated with estrogens, e.g., acute myeloid leukemia (AML), while mutations in unregulated genes are more likely to be associated with AML.



Molecular mechanisms of estrogen carcinogenesis.

  • J. YagerJ. Liehr
  • Biology, Medicine
    Annual review of pharmacology and toxicology
  • 1996
The examples demonstrate that the parent compounds and their metabolites cause both nongenotoxic cell proliferative effects as well as direct and indirect genotoxic effects, which illustrates the complex nature of estrogen carcinogenesis.

Molecular Mechanisms of Estrogen Carcinogenesis

The examples demonstrate that the parent compounds and their metabolites cause both nongenotoxic cell proliferative effects as well as direct and indirect genotoxic effects, which illustrates the complex nature of estrogen carcinogenesis.

Estrogen and the risk of breast cancer.

Experimental data strongly suggest that estrogens have a role in the development and growth of breast cancer and the alkylation of cellular molecules and the generation of new breast cancer cells.

Polymorphisms of estrogen synthesizing and metabolizing genes and breast cancer risk in Japanese women.

  • Y. MiyoshiS. Noguchi
  • Biology, Medicine
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
  • 2003

Genotoxic metabolites of estradiol in breast: potential mechanism of estradiol induced carcinogenesis

Tissue-specific synthesis and oxidative metabolism of estrogens.

Evidence in support of the role of P4501B1 as the 4-hydroxylase expressed in human breast tissue is reviewed and the hypothesis that sufficient E2 may be present in tissue for formation of catechol metabolites that are estrogenic and which form genotoxic species at levels that may contribute to estrogen carcinogenesis is questioned.

Endogenous estrogens as carcinogens through metabolic activation.

  • J. Yager
  • Biology
    Journal of the National Cancer Institute. Monographs
  • 2000
It is concluded that factors will have to be identified through additional mechanistic studies and that, as they are identified, they can be incorporated into future molecular epidemiologic studies designed to determine their actual impact on cancer risk in human populations.

Chapter 3: Endogenous Estrogens as Carcinogens Through Metabolic Activation

Evidence shows that the catechols themselves are signaling molecules that work through the estrogen receptor that give rise to reactive quinones capable of forming direct adducts with glutathione and purines in DNA and of redox cycling to generate reactive oxygen species that can cause oxidative damage.

Relative imbalances in estrogen metabolism and conjugation in breast tissue of women with carcinoma: potential biomarkers of susceptibility to cancer.

The level of catechol estrogen quinone conjugates in cases was three times that in controls, suggesting in the cases a higher probability for the quinones to react with DNA and generate mutations that may initiate cancer.

Crosstalk between estrogen receptor and growth factor receptor pathways as a cause for endocrine therapy resistance in breast cancer.

Although estrogen deprivation therapy is often effective in ER-positive breast cancer, de novo and acquired resistance are still problematic, as trials of aromatase inhibitors show superior results compared with tamoxifen, especially in tumors overexpressing HER2.