By Christine Haran

For many years, the estrogen-blocking drug tamoxifen has been the standard of care for most women with breast cancer. Now, a recently published study, and new guidelines from a leading organization of cancer specialists, indicate that tamoxifen may not always be the best option.

The study, published December 8 in the British journal The Lancet, suggests that another hormonal drug, called an aromatase inhibitor, is more effective than tamoxifen in preventing the recurrence of breast cancer in postmenopausal women with early-stage breast cancer that is fueled by estrogen. Known as the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial, the study followed more than 9,000 women for five years and looked at tamoxifen alone vs. an aromatase inhibitor called Arimidex (anastrozole) alone vs. the combination of those drugs. The combination was found to be no more effective than tamoxifen alone, and the recently published analysis involved about 1,600 women who were treated for more than five years with either tamoxifen or Arimidex. AstraZeneca, the maker of Arimidex, funded the trial.

The researchers found that women on Arimidex were less likely to have a recurrence, develop cancer in the opposite breast, or to have cancer spread to other parts of their body, than women on tamoxifen. Side effects, such as blood clots, hot flashes and endometrial cancer, were less common with Arimidex, though women who received Arimidex had a higher rate of bone fractures and joint pain than women who took tamoxifen.

The study authors conclude that Arimidex "should be the preferred initial treatment" for postmenopausal women with early-stage hormone-sensitive breast cancer. But the American Society of Clinical Oncology guidelines on aromatase inhibitors released in November do not state that Arimidex should always replace tamoxifen. Instead, the panel wrote that treatment for these women should include an aromatase inhibitor either as the initial therapy—or after tamoxifen.

The guideline authors say that the new study findings do not change their recommendation.

"The ATAC trial shows a small benefit in terms of preventing recurrence but not evidence of the impact on survival," said Eric P. Winer, MD, the director of the breast oncology center at the Dana-Farber Cancer Center and the chair of the ASCO panel that wrote the guidelines. "What is still unclear is whether the best approach is to start with an aromatase inhibitor and continue it for five years or to start with tamoxifen and then follow it with an aromatase inhibitor."

According to Dr. Winer, other studies indicate that taking tamoxifen for two to three years and then switching to an aromatase inhibitor might be better than taking only an aromatase inhibitor.

Both tamoxifen and aromatase inhibitors are hormonal drugs, but they work in different ways. While tamoxifen blocks estrogen receptors on breast cancer cells, aromatase inhibitors suppress aromatase, which is an enzyme that helps produce estrogen in postmenopausal women. Aromatase inhibitors are not thought to be effective in younger women, whose ovaries produce estrogen.

For now, women and their doctors should consider tumor characteristics and side effects when figuring out when to use an aromatase inhibitor, Dr. Winer said. For example, Arimidex might not be the best option for a woman with osteoporosis. Likewise, a woman with a blood clot might not be a candidate for tamoxifen.

"Even though we want a simple answer, with breast cancer...it's unlikely that one size will fit all," Dr. Winer said.