A new study is challenging the practice of giving breast cancer survivors 5 years of tamoxifen therapy to prevent a recurrence of the disease. In a report appearing in the New England Journal of Medicine (Vol. 350, No. 11: 1081-1092), women who switched to the drug exemestane after 2 or 3 years of tamoxifen were less likely to see their cancer return than women who stayed on tamoxifen the full 5 years.

The lead researcher of the trial, R. Charles Coombes, MD, PhD, of Imperial College and Charing Cross Hospital, London, said doctors should consider switching their patients to exemestane after a few years of tamoxifen because of these results.

But other experts said it's still too early to know for sure whether exemestane and drugs like it are a better choice for some breast cancer survivors.

"We cannot make a firm recommendation as to what women should do as a result of this study," said Len Lichtenfeld, MD, Deputy Chief Medical Officer of the American Cancer Society. "There must be more follow-up of the women on this study to answer the many questions that remain about this treatment option."

Most breast cancers grow in response to estrogen. Tamoxifen blocks estrogen receptors on breast cancer cells (although it does not affect overall estrogen levels). Studies have shown that giving tamoxifen after initial breast cancer treatment such as surgery reduces the chance the cancer will return. For many years, doctors have advised most women to take tamoxifen for 5 years after initial treatment.

Exemestane (Aromasin), on the other hand, belongs to a class of drugs called aromatase inhibitors, which work in a slightly different way – they prevent the body from producing estrogen. Because of the way these drugs work, they're only effective in postmenopausal women.

Previous studies of other aromatase inhibitors for breast cancer survivors have suggested they may be at least as good, if not better, at preventing cancer recurrences. Last October, a trial of the aromatase inhibitor letrozole (Femara) found it cut recurrences so dramatically that the trial was stopped early so that all the women involved could be given the drug. Women in that study, though, had already completed 5 years of tamoxifen therapy. Another trial is comparing the aromatase inhibitor anastrozole (Arimidex) directly against tamoxifen therapy. Early results of this study showed a slight advantage in terms of recurrence and survival in the women taking anastrozole.

The latest study involved more than 4,700 postmenopausal breast cancer survivors who had been taking tamoxifen for 2 or 3 years. Half the women continued to take tamoxifen for the full 5 years, while the rest switched to exemestane and took that drug for the remainder of the therapy period.

Three years after the switch, 91.5% of the women on exemestane were still cancer-free, compared to 86.8% of the women still on tamoxifen. Moreover, fewer women on exemestane developed cancer in the opposite breast or other parts of the body. Overall survival was the same between the two groups, but the researchers said it may simply be too soon to see a survival advantage of one drug over the other.

Coombes and his colleagues speculate that switching to exemestane may help women because many become resistant to tamoxifen after a few years.

In the study, women on exemestane had more joint pain and diarrhea than women on tamoxifen, but fewer gynecological symptoms like vaginal bleeding and cramps. Exemestane caused more cases of osteoporosis (bone loss), while tamoxifen caused more blood clots.

But this and previous studies had follow-up periods of only a few years; Lichtenfeld and other experts cautioned that little is known about the long-term effects of aromatase inhibitors. An editorial accompanying the study noted that long-term estrogen deprivation may have negative effects on bone and heart health, as well as sexual and mental function.

"Many more years will be required to fine-tune the risk-benefit assessment of adjuvant aromatase inhibitors," wrote editorialist Martine J. Piccart-Gebhart, MD, PhD, of the Jules Bordet Institute in Belgium.

Doctors who discuss aromatase inhibitors with their patients should be sure to tell them what is not known about the drugs, along with what is, she added.

Piccart-Gebhart said women at high risk of recurrence may well be good candidates for treatment with an aromatase inhibitor after primary therapy. Women at low risk of recurrence, on the other hand, might be better off with the standard 5 years of tamoxifen since more is known about its long-term effects.

Lichtenfeld agreed with that assessment, and stressed that women must consult their doctors before deciding to switch drugs. "We must emphasize that women should be informed of the potential benefits and risks of making such a change in treatment," he said.