Combination of Drugs Lowers Breast Cancer Risk and Enhances Metabolic Health in Rats

Researchers from the University of Michigan have discovered that a combination of bazedoxifene and conjugated estrogens (BZA/CE) can significantly reduce obesity-related factors and improve metabolic health in rat models. This combination shows promise as a potential alternative to tamoxifen, a widely used drug for breast cancer prevention, which is associated with undesirable side effects such as hot flashes and increased risk of type 2 diabetes, especially in women with excess weight.

In a study published in JCI Insight, scientists evaluated the effects of BZA/CE on body weight, fat distribution, and gene expression over eight weeks. The treatment led to notable reductions in body weight, fat accumulation, and fat cell size, particularly in obese rats. Additionally, treated rats exhibited lower triglyceride and cholesterol levels, improved insulin sensitivity, and higher levels of beneficial gut microbes like Faecalbaculum rodentium, which could contribute to better metabolism.

The study also identified multiple genes altered by BZA/CE treatment across lean and obese rats, suggesting complex metabolic and transcriptional changes that could underlie improved health outcomes. Importantly, these effects were more pronounced in obese rats, highlighting the potential of BZA/CE for managing obesity-related breast cancer risk, especially during menopause transition.

Current standard prevention for women at high risk involves tamoxifen, a drug that blocks estrogen receptors to inhibit tumor growth but can cause hot flashes and increase the risk of developing diabetes in overweight women. Since BZA/CE already receives FDA approval for hot flash relief and fracture prevention and is being assessed in phase 2 trials for breast cancer, this combination could become a viable alternative for women at elevated risk, particularly those struggling with obesity.

Future research aims to compare the effects of BZA/CE and other drugs at the gene level in women, to validate these findings and explore its potential as a superior option to tamoxifen for obese women entering menopause transition.

This development offers hope for safer, effective breast cancer prevention strategies that also address metabolic health, especially in populations with increased risk due to weight gain and hormonal changes.