A new study finds that postmenopausal women with early stage breast cancer seem to do better if they take the aromatase inhibitor anastrozole (sold as Arimidex) after surgery instead of tamoxifen. The benefits are so striking that the researchers have recommended that doctors consider Arimidex as the first-line drug prescribed to these women, rather than tamoxifen.

In the Dec. 8 online edition of the Lancet, researchers reported results from the Arimidex, Tamoxifen, Alone or in Combination trial, known as ATAC. This study compared 5 years of tamoxifen with 5 years of Arimidex in 9,366 postmenopausal women with early stage disease. Preliminary results suggested Arimidex outperformed tamoxifen, and these results, after 68 months of follow-up, confirm those findings.

Arimidex did a much better job than tamoxifen in reducing the number of cancer recurrences during the study. And if the cancer did return, it was after a longer period of time in women who took the aromatase inhibitor than in those who took tamoxifen. Women with hormone-receptor positive tumors, the most common type of breast cancer, had especially good results.

In addition, cancers that did return were less likely to appear in a part of the body other than the breast in women who took Arimidex; these women were also less likely to develop cancer in the opposite breast.

"It is crucial for women to reduce their risk of recurrence during the time that their disease is most likely to recur," said Aman Buzdar, MD, deputy chairman of the department of breast medical oncology at M.D. Anderson Cancer Center and vice chairman of the steering committee for the trial. "For all women with breast cancer, the first 5 years following diagnosis presents the time frame in which their risk of recurrence is greater."

Arimidex also caused fewer side effects than tamoxifen. Women on the drug had fewer cases of endometrial cancer, blood clots, stroke, vaginal bleeding, hot flashes, and vaginal discharge. However, they did experience more joint pain and broken bones. Although those side effects can be serious, the researchers said women on Arimidex can take drugs called bisphosphonates to help strengthen their bones.

The researchers did not find significant differences in overall survival between the 2 groups. They noted, though, that the women enrolled in the study had a very good prognosis when they began the study, so it might take longer than 5 years to see a survival benefit.

Because of these good results, the researchers recommend that Arimidex replace tamoxifen as a first-choice treatment for postmenopausal women with hormone-positive breast cancer. (Aromatase inhibitors have not been tested in younger women.)

Len Lichtenfeld, MD, deputy chief medical officer for the American Cancer Society, agreed that Arimidex may be a good first choice drug for many women.

"The results of this trial are clearly impressive," he said. "The data up until this point were suggestive that anastrozole was better than tamoxifen, but the trial was not far along enough to make that conclusion. These results do lead me to believe that anastrozole is better than tamoxifen."

But that doesn't necessarily mean all women on tamoxifen should switch to Arimidex, he cautioned.

"Any individual decision has to be based on a discussion between a woman and her family and her oncologist," he said.

As recently as last month, an expert panel from the American Society for Clinical Oncology (ASCO) updated its recommendations on using aromatase inhibitors to prevent breast cancer recurrence. The panel recommended that all postmenopausal women with hormone-receptor positive breast cancer should receive an aromatase inhibitor at some point – either as initial therapy or after 2 to 5 years of treatment with tamoxifen.

There are still some questions to be answered about the performance of aromatase inhibitors. For instance, the study only looked at anastrozole, one of 3 aromatase inhibitors now available. It is not known if the other 2 drugs, exemestane and letrozole, would show the same type of benefits under these circumstances.

Other studies have compared women who take 5 years of tamoxifen with women who switch to an aromatase inhibitor after either 2 or 3 years or after 5 years of tamoxifen. In those studies, the women who switched to an aromatase inhibitor did better. The researchers say those findings, combined with their own, suggest women shouldn't wait to start on an aromatase inhibitor.

But there have not yet been any studies comparing 5 years of therapy with an aromatase inhibitor to therapy with both tamoxifen and an aromatase inhibitor. Nor is it clear how women would fare if they took an aromatase inhibitor first for some period of time, and then took tamoxifen.

Lichtenfeld said input from other breast cancer experts will also be important to deciding the best treatment course for women.

"There always has to be a certain amount of caution interpreting results of a new study until other experts have had a chance to analyze the data and make their conclusions of what the study means from a practical standpoint," he said.

Arimidex, made by AstraZeneca, is a tablet women take once a day. A 30-day supply costs around $200. Tamoxifen, also made by AstraZeneca, is now available generically. A 30-day supply costs about $40.