Signs that bone drug may block breast tumors

The same mechanism that makes Amgen's new bone drug denosumab an effective treatment for osteoporosis may also mean it could help prevent breast cancer, scientists said on Wednesday.

In a study in the journal Nature, an international team of researchers led by scientists in Austria said that a key mechanism in regulating bone strength is also one that allows the synthetic sex hormones found in hormone replacement therapy (HRT) and contraceptive pills to directly affect mammary cells.

The finding suggests that hormone-induced breast cancer could be blocked by denosumab, the first in a new class of drugs that inhibit a protein that activates bone-destroying cells.

"Further studies will be needed to prove the principle of our findings," said Daniel Schramek, who worked on the research with Josef Penninger at the Institute of Molecular Biotechnology in Vienna.

"But we hope that medical trials using denosumab can be started in the near future to test whether the mouse studies can be directly translated to human breast cancer."

The new findings build on earlier studies by Penninger, who previously uncovered genetic evidence that a protein called RANKL is the master regulator of healthy bones.

Finding exactly the same molecule in breast tissues led the scientists to a new link between sex hormones and breast cancer.

Breast cancer is the most common cancer in women and affects up to one in eight women in Europe and the United States during their lives. It kills about 519,000 people a year.

MOLECULAR LINK

Large studies such as the Women's Health Initiative in 2002 and the Million Women Study found that synthetic sex hormones called progestins used in HRT and in contraceptives can increase the risk of breast cancer.

"Since our results show that the RANKL system is an important molecular link between a synthetic sex hormone and breast tumors, one day women may be able to reduce their risk by taking blocking medicines in advance to prevent breast cancer," Penninger said in statement.

The research team found that a synthetic female sex hormone used in HRT and contraceptive pills can trigger RANKL in breast cells of mice. These mammary cells then start to divide and multiply and fail to die when they should, and stem cells in the breast renew themselves, ultimately leading to breast cancer.

In a second study in Nature, also using mice, scientists at the U.S. biotech giant Amgen found that blocking the mechanism with a drug significantly delayed the formation of mammary tumors, leading to fewer breast cancers.

Blocking the RANKL mechanism not only reduced breast tumor formation but also decreased the spread of cancers to the lungs.

Denosumab is sold as Prolia for osteoporosis and is widely considered the most important growth driver in Amgen's pipeline. It won approval from European regulators in May and from U.S. regulators in June for treatment of the brittle bone disease.