Enzyme fighter works as well as tamoxifen.

A drug that physicians usually prescribe for breast cancer only after the front-line tumor fighter tamoxifen has lost its punch works just as well as that better-known drug, a study of postmenopausal women shows.

The drug, anastrozole, even surpasses tamoxifen in fighting certain kinds of breast cancers--those with estrogen-dependent tumor cells--and causes fewer side effects overall, researchers report in the Nov. 1 CANCER.

Many studies have implicated the female hormone estrogen in breast cancer. Anastrozole disables an enzyme called aromatase, which the body needs to manufacture estrogen, whereas tamoxifen fights cancer by blocking tumor cells from responding to the hormone.

Researchers compared the drugs' effects in two 18-month studies of breast cancer patients in Europe and North America and then combined the data. Overall, the scientists had assigned 511 women with advanced breast cancer to receive daily doses of anastrozole and designated another 510 to get tamoxifen.

During the study, the two oral drugs forestalled cancer's growth for about the same period--an average of 8.5 months in the anastrozole patients and 7 months in the tamoxifen group--before it began to worsen again.

However, anastrozole worked better against hormone-dependent cancers, says study coauthor Aman U. Buzdar, a physician at the University of Texas M.D. Anderson Cancer Center in Houston. In such cancers, tumor cells take up estrogen and progesterone, another female hormone. Estrogen activates genes that encode proteins conducive to cell replication, including that of cancer. Progesterone also seems to boost cancer growth, but its mechanism of action is less well understood.

In up to 60 percent of postmenopausal breast cancer cases, tumor cells display estrogen receptors on their surfaces, an indication that they at least in part depend on estrogen, Buzdar says.

In women who had tumors that tested positive for estrogen or progesterone receptors, anastrozole stalled the cancer for 10.7 months on average, whereas tamoxifen delayed cancer progression for 6.4 months, Buzdar says.

Both drugs can cause side effects, such as nausea, diarrhea, and hot flashes. In this study, anastrozole produced about half as many blood clots--a rare but serious complication--as tamoxifen did.

Another recent study suggests that letrozole, a drug that also disables the aromatase enzyme, also thwarts breast cancer.

"There's a significant advantage to having these aromatase inhibitors instead of tamoxifen," says William R. Miller, an experimental oncologist at the Western General Hospital in Edinburgh. "In the past, we regarded tamoxifen as being the gold standard of [hormonal] therapy. It does look as if these newer agents are superior." About one in eight women in the United States will develop breast cancer.

Because anastrozole and tamoxifen work by different biological mechanisms, some scientists believe patients might benefit from taking both simultaneously. In a trial still under way, an international team of scientists is monitoring patients getting tamoxifen, anastrozole, or a combination of the two. That study will also analyze the drugs' effects on patients with earlier stages of breast cancer than those of the women covered by the new report. Some preliminary results are expected later this year.

AstraZeneca, based in Wilmington, Del., markets anastrozole under the trade name Arimidex and also makes tamoxifen. Physicians have used tamoxifen against breast cancer since the 1970s. The U.S. Food and Drug Administration approved anastrozole and letrozole as cancer treatments in 1996 and in 1997, respectively.