Tamoxifen has been used for so long to treat breast cancer that most of us assumed we knew everything that we needed to know about it—including how long women should take it. But yesterday at the San Antonio Breast Cancer Symposium we all learned something new when researchers presented results from the ATLAS trial (Adjuvant Tamoxifen: Longer Against Shorter).
This large international trial included 6,846 women with early stage hormone-sensitive breast cancer who already had taken tamoxifen for five years. Half of the women took tamoxifen for five more years; the other half took a placebo. The results: After following the women for 10 years, the study found that the women who stayed on tamoxifen the additional five years were less likely to have a recurrence or die of breast cancer than were the women who had been on the placebo. Specifically, there were 617 recurrences and 331 deaths that occurred among the 3,428 women who stayed on tamoxifen compared to 711 recurrences and 397 deaths among the 3,418 women who were on the placebo.
This is not what most of us would have predicted—which again shows why clinical trials are so important. It also means we are now confronted with new questions about how best to use tamoxifen, and the aromatase inhibitors, to treat early-stage breast cancer.
The NSABP B-14 study told us that five years of tamoxifen was better than ten, which is what gave us our current standard of care: five years. Subsequently, when the aromatase inhibitors were compared against tamoxifen in clinical trials for early stage breast cancer in postmenopausal women, both drugs were given for five years. It wasn’t that we knew five years of an AI was best. We based what we did on what we had learned about tamoxifen. In these studies, the AI came out slightly ahead. So we changed the standard of care, recommending that postmenopausal women take an AI instead of tamoxifen. But then we learned that taking tamoxifen for two to three years and then an AI for the next two to three years was better than five years of an AI. And that became a new recommendation for postmenopausal women.
Throughout, for premenopausal women (who can’t take an AI because it’s only effective in postmenopausal women) the standard of care never changed: tamoxifen for five years. Now, it will.
For postmenopausal women there will also be new things to consider:
For postmenopausal women, is ten years of tamoxifen better than five years of tamoxifen and then five years of an AI? More studies will be needed to answer this question.
Should postmenopausal women go back on tamoxifen for five years after finishing their AI? Maybe. An AI keeps testosterone from being converted into estrogen, so it decreases estrogen throughout the body. But tamoxifen works in a different way. It blocks the estrogen receptor on cancer cells, but acts like an estrogen in the bone, liver and uterus. So, it would be easier to stay on longer.
What about other risks and benefits? Tamoxifen decreases cholesterol, and improves bone density, which is good for both pre- and postmenopausal women. The biggest risk is uterine cancer. This is less of a concern for premenopausal women—their risk of developing the disease is low to begin with—and this study did not find that tamoxifen increased their risk. However, the risk did increase in postmenopausal women. It’s not a huge risk, but it's real.
What should you do? It all depends on whether you are premenopausal or postmenopausal. If you are premenopausal and do not go into menopause during your five years on tamoxifen, then it makes sense to stay on it another five years. If you are postmenopausal, it depends on what you can tolerate. If the side effects of the AI are too much, it makes sense to go back on tamoxifen.