Post-menopausal women with hormone-sensitive early breast cancer may soon benefit from another treatment option with fewer side effects than the standard drug now available.

The results of a recent study, reported this week in The Lancet (Vol. 359: 2131-2139), suggested that anastrozole, also called Arimidex, could be effective in this group of women.

Researchers from the University College London, UK, conducted an international, five-year study known as the ATAC trial (anastrozole, tamoxifen alone, or in combination). The study included 9,366 post-menopausal women from 21 countries who had undergone breast cancer surgery.

The study compared tamoxifen — standard therapy after surgery for postmenopausal women with hormone sensitive breast cancer — to anastrozole alone and to a combination of both drugs. The researchers wanted to look at the safety of the drugs and how well they worked.

Anastrozole, made by AstraZeneca, first became available in 1996. Referred to as an aromatase inhibitor, it has been shown to lower estrogen levels in post-menopausal women. Tamoxifen, or Nolvadex, also is made by AstraZeneca. It has been used to treat breast cancer for more than 20 years.

The side effects of tamoxifen include an increased risk of endometrial cancer and blood clotting, as well as hot flashes, vaginal discharge, and vaginal bleeding. Anastrozole has been linked with joint disorders.

Of the study participants, 3,125 were randomly assigned anastrozole; 3,116 were assigned tamoxifen; and 3,125 were assigned a combination of both drugs. The average follow-up was about 33 months.

The three-year, disease-free survival rate (the percentage of women with no evidence of cancer after three years) was 2% greater among women taking anastrozole (89.4%) compared with those taking tamoxifen (87.4%).

Combination therapy with both drugs showed no additional benefit compared with women given tamoxifen, and was actually worse when compared to anastrozole alone.

Anastrozole was linked with fewer cases of endometrial cancer, vaginal bleeding and discharge, stroke, blood clots, and hot flashes than was tamoxifen. However, tamoxifen was significantly better tolerated than anastrozole with regard to joint disorders and bone fractures.

"An important consideration at this time is how to treat newly diagnosed patients," said Michael Baum, MD, lead investigator of the study. "An overall assessment of the benefit versus the harm, based on current data, supports the use of anastrozole for the adjuvant treatment of early breast cancer in post-menopausal women."

Jerome Yates, MD, MPH, national vice president for research for the American Cancer Society (ACS) and a specialist in treating cancer in the elderly, said this study is an important step in finding more effective breast cancer treatments with fewer side effects.

"It [the study] is a little difficult to interpret because one would expect that if the drug really conferred an advantage, the combination would show an advantage over tamoxifen alone," Yates said. "Therefore, you have to speculate that with the combination of tamoxifen and anastrozole, tamoxifen must confer a disadvantage because it looks the same as the tamoxifen arm."

Yates also pointed out that because anastrozole does not produce the side effects associated with tamoxifen, the drug may benefit patients from a quality of life standpoint, provided that the joint problems linked with anastrozole do not prove to be a serious problem in the long run.

"The bottom line is anastrozole looks at least as active as tamoxifen, maybe more active, but longer term follow-up is going to be necessary," said Yates.

The same conclusion was reached recently by a panel of experts at the annual meeting of the American Society of Clinical Oncology (ASCO). According to the ASCO Web site, "Overall, the panel considers the results of the ATAC trial and the extensive supporting data to be very promising but insufficient to change the standard practice at this time (May 2002).

The panel also noted that there was not enough evidence to suggest that women now on tamoxifen should switch: "Outside of a clinical trial, women who are taking adjuvant tamoxifen and have not experienced significant side effects should continue tamoxifen therapy for a total of five years."

The study authors also said that longer follow-up is needed before a final benefit and risk assessment can be made, but said that "evidence from this first analysis of the ATAC trial is encouraging and these results could be as significant to breast cancer treatment as the results first seen with tamoxifen nearly 20 years ago."