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Metformin and Chemoprevention: Potential for Heart-Healthy Targeting of Biologically Aggressive Breast Cancer
Veronica C Jones1, Eric C Dietze1, Tijana Jovanovic-Talisman1
1City of Hope Comprehensive Cancer Center, Duarte, CA, United States.
Abstract:
Currently, tamoxifen is the only drug approved for reduction of breast cancer risk in premenopausal women. The significant cardiovascular side effects of tamoxifen, coupled with lack of a survival benefit, potential for genotoxicity, and failure to provide a significant risk-reduction for estrogen receptor-negative breast cancer, all contribute to the low acceptance of tamoxifen chemoprevention in premenopausal women at high-risk for breast cancer. While other prevention options exist for postmenopausal women, there is a search for well-tolerated prevention agents that can simultaneously reduce risk of breast cancers, cardiovascular disease, and type-2 diabetes. Metformin is a well-tolerated oral biguanide hypoglycemic agent that is prescribed worldwide to over 120 million individuals with type-2 diabetes. Metformin is inexpensive, safe during pregnancy, and the combination of metformin, healthy lifestyle, and exercise has been shown to be effective in preventing diabetes. There is a growing awareness that prevention drugs and interventions should make the "whole woman healthy." To this end, current efforts have focused on finding low toxicity alternatives, particularly repurposed drugs for chemoprevention of breast cancer, including metformin. Metformin's mechanisms of actions are complex but clearly involve secondary lowering of circulating insulin. Signaling pathways activated by insulin also drive biologically aggressive breast cancer and predict poor survival in women with breast cancer. The mechanistic rationale for metformin chemoprevention is well-supported by the scientific literature. Metformin is cheap, safe during pregnancy, and has the potential to provide heart-healthy breast cancer prevention. On-going primary and secondary prevention trials will provide evidence whether metformin is effective in preventing breast cancer.
Insights
Metformin, a diabetes drug, shows promise for breast cancer prevention in premenopausal women due to its low toxicity and potential to reduce cardiovascular disease and type-2 diabetes risk.
Area of Science:
- Oncology
- Pharmacology
- Preventive Medicine
Background:
- Tamoxifen is the sole breast cancer risk reduction drug for premenopausal women, but has significant cardiovascular side effects and limited efficacy for certain breast cancer subtypes.
- There is a need for well-tolerated breast cancer prevention agents that also address cardiovascular disease and type-2 diabetes risk.
- Metformin, a widely used diabetes medication, is being investigated as a repurposed drug for breast cancer chemoprevention due to its safety profile and potential benefits.
Purpose of the Study:
- To explore the potential of metformin as a chemopreventive agent for breast cancer in premenopausal women.
- To evaluate metformin's safety and efficacy in reducing breast cancer risk, alongside its impact on cardiovascular health and type-2 diabetes.
- To assess the mechanistic rationale for using metformin in breast cancer prevention, focusing on its effect on insulin signaling pathways.
Main Methods:
- Review of existing scientific literature on metformin's mechanisms of action and its effects on insulin signaling.
- Analysis of metformin's pharmacological properties, including its safety, tolerability, and cost-effectiveness.
- Consideration of ongoing clinical trials investigating metformin for primary and secondary breast cancer prevention.
Main Results:
- Metformin's complex mechanisms include lowering circulating insulin, which is implicated in aggressive breast cancer growth and poor survival.
- Metformin is inexpensive, safe during pregnancy, and has demonstrated effectiveness in preventing diabetes.
- The drug presents a potential for simultaneous breast cancer and cardiovascular disease risk reduction.
Conclusions:
- Metformin is a promising candidate for breast cancer chemoprevention, particularly for premenopausal women seeking a low-toxicity alternative to tamoxifen.
- Its potential to improve overall health by addressing breast cancer, cardiovascular disease, and type-2 diabetes aligns with the "whole woman healthy" approach.
- Further evidence from ongoing primary and secondary prevention trials is crucial to confirm metformin's efficacy in preventing breast cancer.
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