Ask an Expert: Tamoxifen vs. Arimidex?

Q: What can you tell me about Arimidex vs. tamoxifen? Should a person on tamoxifen switch to Arimidex? And is there any benefit to taking Arimidex after five years on tamoxifen?

Answer from the expert staff of breast cancer research at the Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center:

In December 2001, early results from the ATAC (Arimidex or Tamoxifen Alone or in Combination) trial were presented at the San Antonio Breast Cancer Symposium. The ATAC study involved over 9,000 postmenopausal early breast cancer patients who were treated with tamoxifen (Nolvadex), anastrozole (Arimidex) or both for five years. After three years of follow-up, Arimidex treatment alone demonstrated superiority to tamoxifen or the combination.

In December 2002, updated results from the ATAC study were presented. Data from an additional year of follow-up showed that the improved outcomes offered by Arimidex are only increasing over time.

Both Arimidex and tamoxifen work by exerting an effect on estrogen, which feeds the majority of breast cancers and helps them grow. Arimidex belongs to a class of drugs called aromatase inhibitors, which limit the amount of estrogen the body produces in postmenopausal women. Arimidex works by preventing the conversion of steroids made by the adrenal gland into estrogen.

In a woman who has gone through menopause, the adrenal gland is the largest source of estrogen. Arimidex doesn't work in women who are premenopausal because their ovaries make most of their estrogen.

Tamoxifen belongs to a class of drugs called selective estrogen receptor modulators (SERMs), which work by blocking estrogen from binding to its receptors in the breast. This drug works as well in both premenopausal and postmenopausal women.

With an average of four years of treatment on the ATAC study, hormone receptor-positive participants taking Arimidex were 22 percent more likely to be cancer-free than those taking tamoxifen (304 patients on Arimidex vs. 363 patients on tamoxifen experienced recurrence). In addition, the absolute reduction of risk among those taking Arimidex compared to those taking tamoxifen increased from 1.7 percent at three years of follow-up to 2.9 percent at four years of follow-up. These are small but important differences, and the most significant result is that the gap is increasing over time.

As more study results become available, the curves will probably continue to diverge, and we expect that over another five or ten years, we’ll see an even greater difference between the effectiveness of the two drugs. We also expect that Arimidex will improve overall survival rates, because we’re seeing fewer recurrences in distant organs among women taking Arimidex.

There haven’t been many breast cancer-related deaths so far among study participants, so we haven’t yet observed a difference in survival. The ATAC study also indicated that Arimidex is better tolerated than tamoxifen.

Both drugs cause hot flashes, but unlike tamoxifen, Arimidex does not cause blood clots or increase the risk of uterine cancer. However, there is a down side to being on Arimidex. Women taking this drug have more problems with bone fractures. Tamoxifen blocks estrogen in the breast, but it acts like a weak estrogen outside the breast, so it stimulates bone and keeps it from getting thin. Arimidex, on the other hand, works by preventing the production of estrogen. It doesn’t have any estrogen-like effects, so women taking this drug have more bone thinning and fractures.

This side effect shouldn’t be taken lightly, as bone fractures can lead to serious complications, especially in older women. If a woman has a history of osteoporosis, Arimidex may still be the best choice for her. I think that all women should have a bone density test before they start on Arimidex. If a woman’s bone density is low, or if it drops while she is taking Arimidex, she should consider taking calcium supplements or prescription drugs, like Zometa or Fosamax, that prevent bone loss.

Another down side to Arimidex is that it’s twice as expensive as tamoxifen, and this may be an issue for women who don’t have prescription coverage. I recommend Arimidex to most of my postmenopausal patients who have not yet started either drug. Arimidex offers a small but real improvement over tamoxifen, and in general, side effects are minimal.

A woman who is choosing between Arimidex and tamoxifen should discuss the benefits and risks of each with her physician, including a review of her bone density history. If a postmenopausal woman has been on tamoxifen for just a couple of months, she could consider switching to Arimidex. However, if she has been on tamoxifen for a year or more I wouldn’t necessarily recommend switching.

Although a recent study suggested there may be some benefit to switching, more research is needed. We don’t know much yet about the benefits of switching, and we know for certain that it is beneficial to be on tamoxifen for five years. Talk with your doctor about whether switching from tamoxifen to Arimidex might be right for you.

If a woman completes five years of tamoxifen therapy and is interested in Arimidex, she could consider participating in a clinical study addressing the issue of additional treatment with drugs like Arimidex.

Last updated: December 2003

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