Tamoxifen Alternative a Two-Edged Sword

A European study pushes a new kind of drug closer to replacing the old standard, tamoxifen, in preventing the return of breast cancer after surgery.

However, experts say there are important questions still to be answered about the medication.

Anastrozole Could Take Center Stage

The drug is anastrozole, which is a member of an emerging family of breast cancer drugs called aromatase inhibitors. Like tamoxifen, it is used against the great majority of breast cancers whose growth depends on the sex hormone estrogen. Tamoxifen blocks cell receptors for estrogen, while anastrozole inhibits the activity of aromatase, an enzyme involved in the production of estrogen.

Tamoxifen has been a staple of breast cancer treatment for years; one expert estimated recently that it has saved the lives of 400,000 women. However, its side effects—most notably an increased risk of endometrial cancer—have spurred a search for alternative drugs that would be as effective but have fewer side effects.

Comparing Side Effects

A report on the European study, appearing in The Lancet, says a trial involving nearly 10,000 women who underwent breast cancer surgery shows that anastrozole appears to be at least as effective as tamoxifen and avoids most of its side effects. However, anastrozole, sold under the brand name Arimidex, has side effects of its own.

In a follow-up period averaging just shy of three years, anastrozole was slightly more effective in preventing recurrence of breast cancers. In all, 87.4 percent of the women given tamoxifen were alive and disease-free after that time, compared to 89.4 percent of those given anastrozole. Disease-free survival for a third group of women who got both drugs was identical to those for tamoxifen alone.

Anastrozole treatment significantly reduced the side effects associated with tamoxifen—endometrial cancer, vaginal bleeding, hot flushes, heart disease, and stroke. However, anastrozole was associated with a higher incidence of fractures and musculoskeletal problems.

Long-Term Follow Up Is Needed

"Longer follow-up is required before a final benefit-risk association can be made," the journal report says, and Dr. Clifford A. Hudis, chief of the breast cancer medical service of Memorial Sloan-Kettering Cancer Center in New York City, agrees.

The two aromatase inhibitors now available—the other one is letrozole—"have largely replaced tamoxifen as first-line therapy in the United States," Hudis says, meaning they are given when surgery alone is not effective. And as adjuvant therapy, to prevent recurrence, "this trial suggests the possibility that anastrozole may be superior," he says.

However, the follow-up period in the European trial was not long enough to clinch the case for anastrozole, Hudis says. "This will be a moving target over the next few years," he says. We may find more of a benefit, and we have to find out more about long-term toxicities."

Tamoxifen Remains the Appropriate Treatment

At the moment, he says, "tamoxifen remains the appropriate treatment, but there are places and situations where one might consider an aromatase inhibitor."

One thing that concerns Hudis is that some women might not take tamoxifen because of a fear of endometrial cancer. In the European study, 13 of the 3,094 women taking tamoxifen developed endometrial cancer, compared to three of the 3,092 taking anastrozole and 10 of the 3,097 taking both drugs. "It would be tragic if someone does not take tamoxifen for that reason," Hudis says.

Jan Platner, director of programs at the National Breast Cancer Coalition, who served on the technical assessment committee of the European study, says, "We are very concerned about long-term follow-up."

One of her concerns is the bone loss and fractures associated with anastrozole. "Even if it occurs in just a small percentage of cases, it is a very serious side effect," she says. "Also, we don't know what the long-term effect will be of shutting down estrogen production in terms of cognitive function. And we don't know how long a woman has to stay on anastrozole. There are so many questions this study raised, rather than answering."

The hope is that several studies now under way will give the answers, she says.

Always consult your physician for more information.