USC study shows raloxifene may increase ovarian cancer growth rate

July 03, 2001

LAUSANNE, SWITZERLAND, July 3-- The drug raloxifene may increase the growth rate of ovarian cancer and its risk of recurrence, according to researchers from the Keck School of Medicine of the University of Southern California.

Speaking at the European Society of Human Reproduction and Embryology's annual meeting, David Tourgeman, M.D., assistant professor of obstetrics and gynecology at the Keck School, presented data on the effects of raloxifene both alone and in combination with estradiol on ovarian cancer cell lines in the laboratory.

Raloxifene is a selective estrogen receptor modulator (SERM) that has been approved in the United States for use in patients with osteoporosis but has also been looked at as a possible agent for women needing estrogen replacement therapy (ERT). Past research has shown that raloxifene actually has antiestrogenic effects in human breast cancer cells, making it a potentially safe ERT alternative for women who have had breast cancer. In addition, it doesn't seem to increase the risk of uterine cancer in postmenopausal women.

To date, however, not much work has been done on the drug's affects on ovarian cancer, despite the fact that ovarian cancer, too, is a hormone-driven disease, noted Tourgeman.

Along with Richard Paulson, M.D., Keck School professor of obstetrics and gynecology, and their USC colleagues, Tourgeman found that both raloxifene and estradiol stimulate cell growth in ovarian adenocarcinoma cells that carried estrogen receptors on their cell surface (ER+ cells)--and that the drugs' effects occur both when they are given independently and in combination. The cells were exposed to an amount of raloxifene equivalent to that which would be received by the usual 60 mg oral dose of the drug.

"To our knowledge, this is the first time that the effect of raloxifene on ovarian cell lines has been evaluated," said Tourgeman. He notes that there is an ongoing debate as to whether the presence of estrogen receptors on the tumor cells means that estrogen would necessarily cause an ovarian tumor to grow or reappear. Still, he says, "as up to 60 percent of epithelial ovarian cancers and a smaller percentage of anaplastic or recurrent ovarian cancers will be ER+, the most appropriate approach would be one of caution. In contrast to the clinical management of women with a history of breast cancer, raloxifene may not be a good alternative to ERT in women with ER+ ovarian cancer."

Both he and Paulson, however, stressed that this finding does not diminish the recognized benefits of ERT in general for strengthening bone, protecting the cardiovascular system and improving cognition.

That is why, Paulson says, "it would be premature to withhold all forms of ERT from patients with a history of ovarian cancer on the basis of these findings." He and Tourgeman intend to evaluate raloxifene in other cell types to see if it has similar effects. In addition, says Paulson, the hope is that this study will serve as an impetus to other researchers to undertake epidemiologic studies that would evaluate the possible association between raloxifene and ovarian cancer.
"Agonistic Effects of Raloxifene on the Growth of Ovarian Adenocarcinoma (OVCAR-3) Cells." D.E. Tourgeman, C.A. Amezcua, R. Boostanfar, F.Z. Stanczyk, J. Felix, R.J. Paulson.

University of Southern California

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