Researchers at Washington University School of Medicine in St Louis, US, are evaluating osteoporosis drug denosumab in a Phase II clinical trial to prevent breast cancer in women.

The National Cancer Institute (NCI) at the National Institutes of Health (NIH) has granted $3m to support the five-year trial, which will investigate the drug’s ability to reduce breast density.

Women with dense breasts are at a four to six times greater risk of developing breast cancer compared to those with a lower breast density.

In 2010, denosumab received US Food and Drug Administration (FDA) approval to treat osteoporosis. The new trial will assess the drug’s potential to lower breast density in premenopausal women with the aim of preventing breast cancer in the future.

Washington University School of Medicine in St Louis division of public health sciences surgery associate professor Adetunji Toriola said: “About 25% of breast cancers are diagnosed in premenopausal women, but we have only one preventive therapy that has been approved for this group, tamoxifen, a chemotherapy drug that has undesirable side effects, including early menopause.

“While severe side effects are rare, tamoxifen increases a woman’s risk of developing endometrial cancer, blood clots and stroke.”

Researchers aim to develop preventive therapies that can offer an alternative to tamoxifen.

For the Phase II trial, the team will enrol 210 volunteers receiving annual screening mammography at Siteman Cancer Center. Participants must be aged 40 and above, cancer-free, premenopausal, and have dense breasts.

Denosumab is designed to inhibit a molecular signalling pathway called RANK, which is linked to bone remodelling regulation, the development of fibrous mammary gland structures, and breast cancer in experimental models.

Toriola added: “The safety and effectiveness of this drug is well established in its use as an FDA-approved therapy to prevent osteoporosis and bone fractures in older women.

“So we hope that denosumab will provide an additional prevention option for women with dense breasts who are at high risk of developing breast cancer.”

The drug comes with side effects such as low calcium levels, muscle pain and degeneration of the jaw bone, which is said to be resolved after discontinuing the drug.