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Updated: Jul 15, 2026
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Translational approaches for the prevention of estrogen receptor-negative breast cancer
1Departments of Medicine and Molecular and Cellular Biology, Breast Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Abstract:
Breast cancer prevention has focused heavily on endocrine interventions using selective estrogen receptor modulators and aromatase inhibitors. Tamoxifen, the stereotypical selective estrogen receptor modulator, significantly reduces the breast cancer incidence in high-risk women. Selective estrogen receptor modulators and aromatase inhibitors, however, only prevent the development of estrogen receptor-positive breast cancer and have no effect in reducing the risk of estrogen receptor-negative breast cancer, which has poor prognosis. Thus, preventive therapies for estrogen receptor-negative breast cancer are clearly needed. Recently, a number of novel chemopreventive agents targeting nonendocrine pathways have been developed and shown to prevent estrogen receptor-negative mammary tumorigenesis in animal models. These agents include rexinoids, selective cyclooxygenase-2 inhibitors, tyrosine kinase inhibitors, and others. In this review, we discuss the effects of selective estrogen receptor modulators and aromatase inhibitors, as well as novel agents targeting nonendocrine pathways. We also discuss the promise of combining these agents for the effective prevention of all forms of breast cancer.
Insights
Current breast cancer prevention targets estrogen-driven tumors. Novel therapies are needed for estrogen-receptor-negative breast cancer, prompting research into nonendocrine agents and combination strategies for comprehensive prevention.
Area of Science:
- Oncology
- Pharmacology
Background:
- Endocrine therapies like tamoxifen (selective estrogen receptor modulator) are effective for estrogen receptor-positive breast cancer.
- Estrogen receptor-negative breast cancer lacks effective prevention and has a poor prognosis.
Purpose of the Study:
- To review current endocrine therapies for breast cancer prevention.
- To explore novel chemopreventive agents targeting nonendocrine pathways for estrogen receptor-negative breast cancer.
- To discuss the potential of combining therapies for broad breast cancer prevention.
Main Methods:
- Review of existing literature on selective estrogen receptor modulators and aromatase inhibitors.
- Examination of preclinical data for novel agents targeting nonendocrine pathways (e.g., rexinoids, COX-2 inhibitors, tyrosine kinase inhibitors).
- Analysis of strategies for combining endocrine and nonendocrine therapies.
Main Results:
- Selective estrogen receptor modulators and aromatase inhibitors are ineffective against estrogen receptor-negative breast cancer.
- Emerging nonendocrine agents show promise in preventing estrogen receptor-negative mammary tumors in animal models.
- Combination therapies may offer a synergistic approach to prevent all breast cancer subtypes.
Conclusions:
- There is a critical need for preventive strategies against estrogen receptor-negative breast cancer.
- Novel nonendocrine agents represent a promising avenue for preventing this aggressive subtype.
- Combining endocrine and nonendocrine therapies holds potential for comprehensive breast cancer prevention.
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