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Clinical Trial Results

Summaries of Newsworthy Clinical Trial Results
  • Posted: 06/03/2011

Five Years of Tamoxifen Continues to Benefit Women 15 Years after Treatment

Summary

In a large randomized clinical trial, women with early-stage breast cancer who received 5 years of adjuvant treatment with tamoxifen had better outcomes up to 15 years after the start of treatment than those who received 2 years of tamoxifen therapy. Risks of cancer recurrence, of cancer in the other breast, and of death from breast cancer were all lower in women who took tamoxifen for 5 years than in those who took it for 2 years.

Source

Journal of Clinical Oncology, published online March 21, 2011 (see the journal abstract).

Background

The drug tamoxifen, a type of hormone therapy, is a standard treatment for women with estrogen receptor-positive breast cancer. A 2005 meta-analysis (see the journal abstract) indicated that 5 years of tamoxifen treatment is better than 1 to 2 years of treatment at preventing breast cancer recurrence and death in women with early breast cancer. However, these studies had a mean follow-up of 5 years, and the long-term benefits or risks of 5 versus fewer years of tamoxifen have not been clear.

The Study

The Cancer Research UK “Over 50s” clinical trial enrolled 3,449 women aged 50 to 81 years with early-stage breast cancer that could be removed surgically. The study recruited participants between 1987 and 1997 from 71 hospitals in Europe and Asia. Just over half the women had already gone through menopause.

After surgery, all women received tamoxifen for 2 years. After 2 years, the researchers randomly assigned the participants to either stop tamoxifen or to continue for another 3 years, for a total of 5 years of treatment. The researchers collected data on cancer recurrences, new cancers, heart disease, and deaths from any cause through April 2010. At that time, the median follow-up was 10 years, and 25 percent of the participants had been tracked for more than 14 years.

The study was led by Allan Hackshaw, MSc, from Cancer Research UK and the University College London Cancer Trials Centre, and was funded by Cancer Research UK and the University College London Hospital Comprehensive Biomedical Research Centre.

Results

After random assignment, 1,724 women stopped tamoxifen after 2 years, and 1,725 were scheduled to continue for 5 years. Treatment compliance—the proportion of women who took tamoxifen for the entire scheduled time—was high in both arms.

Women who took tamoxifen for 5 years had a 17 percent lower risk of cancer recurrence and a 9 percent lower risk of death from breast cancer than women who took tamoxifen for only 2 years. They also had a 30 percent lower risk of developing cancer in the contralateral (other) breast.

The researchers calculated that for every 100 women who received tamoxifen for 5 instead of 2 years, almost 5 fewer recurrences would be seen 10 years after treatment. Fifteen years after treatment, almost 6 fewer recurrences would be seen.

Differences in both overall survival and deaths from breast cancer also favored the longer duration of tamoxifen treatment for up to 12 years after treatment. The benefits of 5 years of tamoxifen were seen in both premenopausal and postmenopausal women.

In an unplanned analysis by age, the authors found that women aged 50 to 59 who took tamoxifen for 5 years had a 35 percent lower risk of cardiovascular events, such as heart attack, and a 59 percent lower risk of death from cardiovascular events than women in the same age group who took tamoxifen for 2 years.

Limitations

Since the analyses of cardiovascular events and related deaths were not planned at the start of the trial, those results “should therefore be regarded with some caution,” stated Kathleen Pritchard, M.D., and Berta Sousa, M.D., from the Sunnybrook Odette Cancer Center in Toronto, Canada, in an accompanying editorial.

However, explained Leslie Ford, M.D., of NCI’s Division of Cancer Prevention, researchers have known for a long time that tamoxifen lowers blood cholesterol levels. “Obviously no one would take tamoxifen just to prevent heart disease, but I would say that these data on cardiovascular effects are reassuring for women. At best, you might have some decrease in cardiovascular disease, and at worst you might see no effect either way,” she explained.

Since the study began back in the 1980s, whether or not all tumors expressed the estrogen receptor was not measured at most centers. Since women with tumors that do not express the estrogen receptor (called estrogen receptor negative tumors) do not benefit from tamoxifen, including some of these women in the trial would have decreased the observed overall benefit.

Comments

Several recent clinical trials have shown that another class of hormone therapy drugs, called aromatase inhibitors, is more effective than tamoxifen at decreasing the risk of recurrence and risk of death from breast cancer. However, aromatase inhibitors are not effective in premenopausal women and so are used exclusively in postmenopausal women.

Aromatase inhibitors also have a different set of side effects than tamoxifen, explained Dr. Ford. “It’s good for women to know that even if they start on an aromatase inhibitor and have to stop because of side effects, there is another alternative—tamoxifen—that still gives tremendous benefits,” she said.

Tamoxifen is also available as a generic drug, added Dr. Ford, and therefore affordable in the developing world.

The message for women from this long-term follow-up study is “To take your pills for as long as they’re prescribed,” concluded Dr. Ford. “Five years of therapy confers benefits for up to 15 years—the benefits last far beyond the last pill.”

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