New drug combination protects women from breast cancer and diabetes without side effects

Women in midlife face a difficult trade-off. Many in their 40s to 60s face a high risk of breast cancer, especially during the transition into menopause. Doctors often prescribe tamoxifen to reduce this risk. The drug works well against cancer, but it often causes severe hot flashes and, in women who are overweight, increases the risk for type 2 diabetes.

This side effect alone pushes many to avoid the drug altogether. That means about one in four women in this age group may go without protection simply because the treatment feels worse than the disease. Researchers may now have a better answer.

A team from the University of Michigan studying a drug combination known as bazedoxifene and conjugated estrogens (BZA/CE) found it could offer similar cancer protection without triggering the same side effects. In fact, their results suggest it may actually help improve body weight, fat metabolism, and gut health—especially in those with obesity.

Tamoxifen prevents breast cancer by blocking estrogen from reaching receptors on cells, which slows or stops tumor growth. But blocking estrogen affects other systems in the body. It leads to hot flashes and can increase insulin resistance, especially in women with higher body weight. That raises the risk of developing type 2 diabetes.

Erin Giles, associate professor of kinesiology, explained the problem clearly. “Although it can reduce their cancer risk, tamoxifen also increases hot flashes and, in women who are overweight, it may increase their risk for type 2 diabetes, which discourages many women from taking it.”

This is where BZA/CE comes in. Already approved by the FDA to treat hot flashes and prevent bone fractures, this combination may offer dual benefits. Not only does it reduce hot flashes, it may also help with weight control and lower breast cancer risk. “We wanted to see whether BZA/CE could work as an alternative to tamoxifen for those who are overweight,” Giles said.

To test the drug combo, scientists used older female rats that had not undergone ovary removal. These rats were given a cancer-causing agent to raise their breast cancer risk. Then, the rats were split into two groups—lean and obese—based on how much fat they carried.

Each group received either BZA/CE or a control treatment for eight weeks. During this time, researchers tracked changes in weight, fat levels, insulin response, and even gut bacteria.

The results were striking. Treated rats weighed less and had lower body fat than untreated rats. In the obese group, the treated animals weighed about 19% less than those given no treatment. Breast tissue in these rats also had fewer and smaller fat cells.

Triglyceride and cholesterol levels fell in the BZA/CE group. Their bodies showed improved insulin sensitivity, suggesting a lower risk for type 2 diabetes. Giles noted, “The levels of triglycerides and cholesterol were also lower, and the treated rats had lower insulin resistance.”

The benefits didn’t stop at fat loss. Researchers found that BZA/CE shifted the makeup of bacteria in the gut toward more beneficial species. Treated rats had more Faecalbaculum rodentium and Odoribacter laneus—microbes linked to better metabolic function.

These microbes can help process food in a way that leads to better glucose control and healthier fat storage. The result may be less inflammation, better hormone balance, and improved energy use by cells.

The drug combination also reversed harmful gene activity patterns linked to cancer in the mammary glands. In obese rats, pathways tied to cell growth were toned down, which suggests a lowered risk of developing tumors.

“Although we didn’t test each drug alone, our results demonstrate that BZA/CE could be superior to tamoxifen for those with obesity who are also undergoing a transition into menopause,” Giles said.

The team now plans to study how the drug combination affects gene expression in women, not just in rats. If similar patterns appear, BZA/CE could soon become a strong option for women at high risk of breast cancer who want protection without the trade-off.

The treatment’s promise lies in its broad effects. Unlike tamoxifen, which focuses only on blocking cancer signals, BZA/CE works across several systems. It reduces hot flashes, lowers body fat, improves gut health, and corrects harmful changes linked to obesity—all while reducing the likelihood of tumor growth.

Right now, BZA/CE is being tested in a phase 2 clinical trial for breast cancer risk reduction. If the results hold up in humans, many more women may finally have an option that helps them feel better, not worse, while protecting against a deadly disease.

Breast cancer remains one of the most common cancers among women, and finding safe, effective prevention strategies is urgent. Nearly 25% of U.S. women between 45 and 60 should consider a prevention drug based on their risk. But many say no to tamoxifen because of how it makes them feel.

This research suggests the future may hold a better option. By addressing not only cancer risk but also common symptoms and metabolic health, BZA/CE could open new doors for preventive care.

Researchers still have more to learn. But for now, they have taken a big step toward giving women more choices—and more comfort—when it comes to staying healthy.

Research findings are available online in the journal JCI Insight.

Note: The article above provided above by The Brighter Side of News.

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