Ospemifine may also help to prevent breast cancer

A tamoxifen-like drug developed by UC Davis and Finnish researchers, now in clinical testing as a treatment for vaginal atrophy, may also help to prevent breast cancer, two preliminary studies suggest.

The studies, based on research in a mouse model of human breast cancer, will be published in the November issue of the Journal of Steroid Biochemistry and Molecular Biology and the December issue of Breast Cancer Research.

"These reports indicate that prevention of breast cancer may be another benefit of the use of ospemifine," said Michael W. DeGregorio, a professor of medicine at UC Davis. "The findings are very encouraging."

DeGregorio is senior author of the November article and a contributing author of the December paper. He has spent the last 20 years developing ospemifene in collaboration with Risto Lammintausta, managing director of Hormos Medical Corp. in Turku, Finland.

Ospemifene is now being developed by QuatRx Pharmaceuticals, an Ann Arbor, Mich.-based biopharmaceutical company that recently merged with Hormos Medical Corp. The drug is expected to enter Phase 3 clinical testing in the United States early next year for the treatment of vaginal atrophy, a common condition among postmenopausal women.

Ospemifene is one of a class of drugs called selective estrogen receptor modulators. The well-known agent tamoxifen, used to prevent breast cancer in women at high risk for the disease, and raloxifen, currently used to prevent bone fractures in women with osteoporosis, belong to the same class.

In the Journal of Steroid Biochemistry and Molecular Biology, DeGregorio and his colleagues at UC Davis compared the ability of ospemifene, tamoxifen and raloxifen to inhibit breast cancer in mice exposed to a carcinogen. Ospemifene and tamoxifen both inhibited breast cancer development: Mice in the ospemifene group were 95 percent less likely than mice in the control group to develop breast cancer. Raloxifen had no such effect.

The second study, led by Jeffrey P. Gregg, an associate professor of pathology and laboratory medicine at UC Davis, reports that in a mouse model, both tamoxifen and ospemifene inhibited the growth and progression of pre-malignant breast lesions that closely resemble human ductal carcinomas in situ. Both these agents decreased the growth of the lesions by reducing the proliferation rate of the precancerous cells.

While similar, tamoxifen, raloxifen and ospemifine have variations in chemical structure that give them unique therapeutic profiles. For example, raloxifen can prevent bone fractures, but it can also cause hot flashes, insomnia and blood clots. Tamoxifen can decrease a high-risk woman's odds of developing breast cancer by half, but the drug also increases the risk of endometrial cancer and can cause the same side effects as raloxifen.

In clinical tests so far, ospemifene appears to have a unique estrogen-like effect on the vagina, yet a neutral effect on the endometrium, or lining of the uterus, and no aggravation or initiation of hot flashes. Results of the Phase 1 and Phase 2 tests, conducted in postmenopausal women in Finland, appear in the journal Menopause in September 2003 and March 2005.

"Dr. Lammintausta and I worked for many years to find a drug that would have beneficial effects in healthy, postmenopausal women but be absolutely safe," said DeGregorio. "We're gratified that this seems to be the case."

Decreased estrogen levels can lead to a thinner, less elastic and more fragile vaginal lining. Known as vaginal atrophy, the problem affects 10 to 40 percent of post-menopausal women. Symptoms may include dryness, itching, burning, irritation, a feeling of pressure, and pain or light bleeding with sex. Estrogen creams, rings, patches or oral supplements are often prescribed to treat vaginal atrophy.