One in eight American women will develop breast cancer during her lifetime. After breast cancer treatment, a woman’s risk for breast cancer recurrence remains elevated.

Because most breast cancers depend on estrogen to grow, decreasing estrogen levels can help protect women from recurrence. Many post-menopausal women take a hormone therapy called tamoxifen (Nolvadex) for five years after breast cancer treatment. Tamoxifen competes with estrogen for receptors that are found on most breast cancers, thereby cutting off the supply of estrogen to the cancer. But studies have found that, while tamoxifen can reduce the recurrence rate in the first five years, it loses its benefit thereafter, and may even become harmful.

Aromatase inhibitors, such as letrozole (Femara), are another class of hormone therapy used to prevent the recurrence of breast cancer. Rather than blocking estrogen from interacting with breast cancer cells, these drugs work by blocking the production of estrogen.

A study in the November 6, 2003 issue of the New England Journal of Medicine found that, after five years of tamoxifen therapy, 2.4 years of letrozole therapy significantly extended the disease-free survival rates of postmenopausal women who’ve had breast cancer. The study was set to go for five years, but was stopped early because the data and safety monitoring committee determined that all the subjects in the study should be immediately offered letrozole.

About the Study

This study included 5,187 postmenopausal breast cancer survivors who had completed five years of tamoxifen therapy. The women were randomly assigned to receive letrozole or a placebo pill daily.

The women had regular evaluations to detect recurrent breast cancers, bone fractures , osteoporosis , heart disease , and adverse effects of letrozole.

The researchers compared the effects of letrozole to placebo on the women’s disease-free survival (living without cancer recurrence or new breast cancer) and overall survival (living with or without cancer recurrence).

The Findings

At the mid-study evaluation, which occurred after 2.4 years, 2.9% of the women in the letrozole group and 5.1% of the women in the placebo group had developed new or recurrent breast cancer. Letrozole decreased the risk of developing a new or recurrent breast cancer by 43%.

The women in the letrozole group had a slightly greater chance of overall survival than the women in the placebo group (96% versus 94%, respectively), but this difference was not statistically significant.

Hot flashes, arthritis , joint pain, and muscle pain were more common in the letrozole group than in the placebo group. Vaginal bleeding was more common in the placebo group. There was a trend, although not significant, toward an increased risk of osteoporosis in the letrozole group.

How Does This Affect You?

Does this study mean all breast cancer survivors should take letrozole after five years of tamoxifen? Not necessarily. Since this study was stopped early, some questions still remain unanswered.

Although there was a trend toward an increase in overall survival in the letrozole group, the study did not go on long enough to determine if letrozole would help the women live longer. It also could not provide information on the optimal duration of letrozole therapy. Future studies will be necessary to assess the long-term effects of letrozole and determine when and how long it should be used.

These findings do, however, suggest that letrozole improves disease-free survival in breast cancer survivors. If you are postmenopausal and have had breast cancer, particularly if it’s being treated with tamoxifen, be sure to contact your doctor. Based on this study, many breast cancer experts will be interested in discussing the benefits and drawbacks of letrozole therapy with their patients.