A Better Option?

By Christine Gorman

What if doctors had a pill that prevents breast cancer and nobody wanted to take it? That has pretty much been the situation with tamoxifen, an estrogen-like drug that was proved in 1998 to cut in half the chance of developing breast cancer if taken for five years by women with increased risk of the malignancy. The trouble is, tamoxifen also triggers menopausal symptoms like hot flashes and slightly increases the chances that a woman will develop blood clots and uterine cancer. As a result, women haven't been too eager to take the medication--nor have many doctors been all that enthusiastic about prescribing it.

Now comes word that another estrogen-like drug, called raloxifene, is as effective as tamoxifen at reducing the risk of breast cancer--at least in high-risk, postmenopausal women--with fewer of those side effects. According to preliminary results from the Study of Tamoxifen and Raloxifene (STAR), raloxifene triggered fewer uterine cancers, blood clots and hot flashes than tamoxifen. It also decreased the chances of developing cataracts.

There are a number of caveats to bear in mind, however. Those results are preliminary and have not yet appeared in a peer-reviewed research journal--although the National Cancer Institute has posted a lot of information on its website cancer.gov/star) Women at high risk of cardiovascular problems were not included in the study since both drugs are known to increase the risk of blood clots. In addition, raloxifene is currently approved only for the treatment and prevention of osteoporosis.

A few clinical uncertainties need to be addressed as well. Tamoxifen reduces the risk of noninvasive breast cancers (ductal carcinoma in situ and lobular carcinoma in situ), while raloxifene does not. "Expert opinion is going to be very important in interpreting this," says Dr. Len Lichtenfeld of the American Cancer Society. "We're certainly looking forward to all the information being examined and discussed."

Having said that, Lichtenfeld notes that the STAR trial is a scientifically rigorous, well-controlled study that involved nearly 20,000 women and was conducted by very reputable researchers. More data will be presented in June at the annual meeting of the American Society of Clinical Oncology. The investigators are also writing a paper to submit to a research journal, but felt it would be unethical to withhold from the group that participated in the STAR trial their overall conclusion that raloxifene was the winner. The women will now find out which drug they were taking, and those on tamoxifen will be given the choice of either staying on that drug or switching to raloxifene.

As for the rest of the population, women who are already weighing the pros and cons of raloxifene for their bone health may decide to add the STAR results to the plus side of the equation. Meanwhile, other studies are under way to determine if a different group of drugs, called the aromatase inhibitors, might be more effective at preventing breast cancer than either tamoxifen or raloxifene. Breast-cancer research is such a fast-moving field that it often seems as though something better is just over the horizon.

TAMOXIFEN VS. RALOXIFENE

o The study included 19,747 postmenopausal women who were at high risk of developing breast cancer

o The participants' risk was about twice as high as that of the average 60- to 64-year-old woman, based on family history, previous breast biopsies and the women's age at first menstruation

o On average, a month's supply of raloxifene costs $75 in the U.S., compared with $100 for tamoxifen