ATLAS: When Research Changes Practice

February 27, 2013 at 10:50 pm Leave a comment


ATLAS put ten years of Tamoxifen to the test.

Each year before the San Antonio Breast Cancer Symposium begins, there is always a buzz about what the big news will be. There is little doubt that in 2012 the findings that garnered the most attention were from the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial , which showed that taking the hormone therapy tamoxifen for 10 years was more effective than taking it for five, the currently recommended treatment.

To understand why this was significant, we need go back to 1995. That’s when the NSABP B-14 study, a U.S. trial comparing 10 years of tamoxifen to five years of the drug, was stopped early because the trial data suggested that not only was 10 years not better— it might even be worse. (More recurrences were seen among the women taking tamoxifen longer.) From that point on, there was no question, at least in the U.S., that tamoxifen should be taken for five years—and no longer.

Outside the U.S., however, questions remained. And in 1996, convinced that the issue was not settled, the Clinical Trial Service Unit (CTSU) at the University of Oxford launched ATLAS, an international trial that enrolled 6,846 women with ER-positive breast cancer who had already taken tamoxifen for five years. Half of the women were randomly assigned to take tamoxifen for five more years. The other half stopped treatment.

As the ATLAS trial group reported at San Antonio and in the Lancet, after about eight years of follow-up, 1,328 breast cancer recurrences and 728 deaths had occurred among all the women in the study. In years five to nine after diagnosis, the number of recurrences and deaths didn’t really differ between the two groups. But that changed once the women were about 10 years out from their diagnosis. At that point, the women who had stayed on tamoxifen were 25 percent less likely to have their cancer recur and 29 percent less likely to die of breast cancer than were the women who had stopped at five. In sum: The risk of dying from breast cancer five to 14 years after diagnosis was 12.2 percent among those who continued on tamoxifen compared with 15 percent among those who stopped — an absolute gain of 2.8 percent, with the greatest benefit 10-14 years after diagnosis.


Dr. Richard Gray

To learn more about the ATLAS trial, BCT spoke with Dr. Richard Gray, the professor of medical statistics at the University of Oxford who presented the findings at San Antonio on behalf of the ATLAS group.

Q: Why did the ATLAS group think that it might be beneficial for women to stay on tamoxifen longer?

A: We didn’t believe there was convincing evidence that taking tamoxifen for longer than five years was worse. The NSABP study did report worse outcome, but that was based on small numbers (1000 patients), and the difference was not extreme, so there was the possibility it could be a chance finding. There is also the complication that if women take tamoxifen for five years and then stop, it will continue to reduce recurrences over the next five years. So if you are comparing 10 years with 5 years, you don’t expect to see benefit for the first few years because of that carryover effect.

Q:  And after 10 years, tamoxifen did?

Yes.  What we found is that you can’t beat that carryover effect for the first five years. [Years five through nine after diagnosis.] But after that you do start seeing the benefit.

Q: Was it difficult to enroll women in the ATLAS trial?

A: It was no harder than recruiting for any trial. The eligibility for ATLAS was women who had taken five years of tamoxifen and who were not sure if they should carry on or not. If you can’t decide, then taking part in a study and having the study make the decision for you can be an attractive option, especially if you are worried that you will make the wrong decision. We didn’t know if carrying on was better than stopping, so we had half continue on and half stop. It is thanks to all these women who took part in ATLAS that we now know that carrying on is best.

Q: What are the implications of your findings for how long a woman should stay on an aromatase inhibitor (AI)?

A: We will need to look at findings from the AI trials now underway to determine if 10 years of an AI is better than five.

Q: Who will benefit most from your findings?

A: About 20 percent of breast cancer is in premenopausal women for whom AIs are not an option. Also some women don’t tolerate the AIs, due to the side effects. So, a lot of women switch to tamoxifen. And there are many countries that prefer to use tamoxifen because it is less expensive. For all of these women we now have evidence that 10 years is better than five.

Entry filed under: Breast Cancer Treatment, Research Results, Tamoxifen.

ATLAS: In Practice From the Director

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