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Tamoxifen slashes serum cholesterol ... but shows link to 'bad' uterine cancers.

Tamoxifen is the most widely used and effective drug for preventing the recurrence of breast cancer (SN:2/22/92, p.124). In 1990, researchers at the University of Wisconsin-Madison showed that it can also yield a "durable" (two-year) 12 percent average decrease in cholesterol. But the researchers didn't know how quickly cholesterol concentrations in blood serum fall once tamoxifen treatment begins. Now, in the Aug. 18 JOURNAL OF THE NATIONAL CANCER INSTITUTE, Richard R. Love and his co-workers at Wisconsin show that serum cholesterol plummets immediately after treatment starts. It took only two weeks for total cholesterol levels to drop an average of 32 milligrams per deciliter of blood -- roughly 12 percent -- in the seven cancer survivors studied.

Many women starting tamoxifen therapy complain about the onset on exaggeration of menopausal side effects -- chiefly hot flashes and vaginal dryness. Such symptoms can prove disturbing enough for some women to discontinue treatment. But if doctors could point to a reduction in a major risk factor for heart disease, Love says, they might convince women to stick with the drug a little longer. And that may be all that's needed. In the April 21 JOURNAL OF THE NATIONAL CANCER INSTITUTE, Love's team reported finding that the severity of hot flashes peaks at about six monts and then wanes.

A potent hormone-like drug, tamoxifen poses some risks of its own. The leading one: development of endometrial cancer, a malignancy of the uterine lining. However, many researchers have all but brushed off the importance of tamoxifen-induced uterine cancers, charging that because they seldom kill, "it's no big deal" (SIN: 4/25/92, p.266). A pair of new studies now forcefully challenges that assessmenyt.

Elvio G. Silva, a pathologist at the University of Texas M.D. Anderson Cancer Center in Houston, examined tissues from 71 breast cancer survivors who later developed uterine cancer. He says his unpublished analysis indicates that, compared with the 56 women who did not take tamoxifen, the 15 who did were 4.7 times more likely to develop serous carcinoma, almost twice as likely to develop mixed mullerian tumors, and 50 percent more likely to develop clear-well carcinoma. the prognosis for any of these three uterine cancers is poor. The tamoxifen users also proved three times as likely to exhibit additional precancerous polyps in the uterus.

"I don't want to scare everybody with this," Silva told SCIENCE NEWS, notingg that the development of uterine cancer among tamoxifen users remains a fairly rare ocurrence. However, he adds, the data now indicate that once a tamoxifen user does develop a uterine cancer, there is a strong likelihood it will be "bad" -- that is, likely to spread and kill.

That's also the conclusion of a study of uterine malignancies in 53 breast cancer survivors, conducted at Yale University School of Medicine. Again, 15 were tamoxifen users.

Estrogen can foster endometrial cancer. But when it does, says Yale pathologist Maria Luisa Carcangiu, such hormone-induced malignancies tend to be low-grade -- that is, unlikely to spread and therefore "curable" through surgery. As a result, she says, "everybody used to say that since tamoxifen acts like an estrogen, any endometrial cancers [it causes] will be low-grade." Her data now refute that.

The interval between the diagnosis of breast and endometrial cancers averaged 12 years in women who had not been treated with tamoxifen, but was only five years for those who had. Moreover, 67 percent of tumors in tamoxifen users were high-grade, compared with 24 percent in the other women. Because the cells of uterine tumors in tamoxifen users also proved uncharacteristic of estrogen-linked malignancies, they may trace to "a different mechanism wof action of tamoxifen on endometrial cells," Carcangiu's group concluded in the March JOURNAL OF CLINICAL ONCOLOGY.

She hopes these new data convince physicians that in tamoxifen patients, "endometrial cancers can kill. In our experience, they did so frequently."
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Title Annotation:drug used to prevent breast cancer recurrence
Publication:Science News
Date:Sep 25, 1993
Words:645
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