Arimidex After Two Years of Tamoxifen Reduces Recurrence in Post-Menopausal Women
Reviewed study: "Arimidex After Two Years of Tamoxifen Reduces Recurrence in Post-Menopausal Women" by R. Jakesz et al., The Lancet, August 6, 2005
Is this for me? If you're a post-menopausal woman with hormone-receptor-positive, early-stage breast cancer and have been taking tamoxifen for one to three years, you might want to read this article.
Background and importance of the study: What's the best hormonal therapy for you if you're a post-menopausal woman with early-stage, hormone-receptor-positive breast cancer? Should you take tamoxifen or an aromatase inhibitor from the start? Or should you take tamoxifen first, and then switch to an aromatase inhibitor later on?
Here is what studies so far have shown. After other forms of therapy (surgery, chemotherapy, and radiation), an aromatase inhibitor is recommended as the first hormonal therapy because it has more benefits and fewer serious side effects than tamoxifen. The American Society of Clinical Oncologists (ASCO) made these recommendations based on results after five years from the ATAC Study of Arimidex (chemical name: anastrozole) and results after two years from the BIG-98 study of Femara (chemical name: letrozole).
But many women were already in the midst of their five-year course of tamoxifen when ASCO issued this recommendation. What should they do—stay on tamoxifen, or switch over to an aromatase inhibitor? If they should switch, when should the switch be made?
A few studies have already looked at these questions. One large study switched women over to Aromasin (chemical name: exemestane). The researchers concluded that switching to Aromasin after 2 to 3 years of tamoxifen significantly improved disease-free survival compared to the standard 5 years of tamoxifen for postmenopausal women with early-stage, hormone-receptor-positive breast cancer. Results from two studies after two years of follow-up showed a benefit from switching to Arimidex after two to three years of tamoxifen rather than taking tamoxifen for five years.
The research reviewed here gives longer follow-up results from these two studies on switching from tamoxifen to Arimidex.
Study design: Two studies, the ABCSG Trial 8 and the ARNO 95 Trial, included 3,224 post-menopausal women in Germany and Austria with hormone-receptor-positive, early-stage breast cancer. The women had mastectomy or breast-conserving surgery and lymph node biopsy. (Some of the women also had radiation therapy, but the researchers did not report how many.)
The women all had been taking tamoxifen for two years. They were randomly divided into two groups:
- In one group, the women switched to Arimidex, which they took for three years.
- In the other group, the women continued to take tamoxifen for three more years, for a total of five years.
The studies were funded by the German Adjuvant Breast Cancer Group and AstraZeneca. AstraZeneca is the maker of Arimidex and Nolvadex (the brand-name form of tamoxifen).
Results: After two and a half years of follow-up, the researchers compared the women who had switched to Arimidex after two years of tamoxifen to the women who remained on tamoxifen for five years. The women who switched:
- had a 40% reduced risk of the cancer coming back in the area that was initially involved, and
- had a 40% reduced risk of developing a new cancer in the other breast. These reduced risks were significant, meaning that they were most likely due to Arimidex and not just to chance.
The chance of living free of disease ("disease-free survival") was about 96% in the group of women who switched, compared to about 93% in the group who didn't. That 3% difference, the "absolute risk reduction," represents a 40% improvement, the "relative risk reduction." (Visit our risk reduction page for more information.)
The researchers also found that the benefits of switching from tamoxifen to Arimidex were not affected by the cancer's hormone-receptor status. This means that it didn't matter whether or not the cancer was estrogen-receptor-positive or progesterone-receptor-positive. Arimidex seemed to have the MOST benefit in women with estrogen-receptor-positive, progesterone-receptor negative cancer, but this finding was not statistically significant.
Women who switched to Arimidex reported twice as many fractures as those who continued to take tamoxifen (34 compared to 16). This difference was significant, meaning that it was most likely due to Arimidex and not just to chance. Women who switched to Arimidex also had fewer blocked blood vessels (2 compared to 9) and endometrial cancers (1 compared to 7). But women who switched to Arimidex had more nausea and bone and joint pain. These differences were also significant.
No difference in overall survival between the two groups was noted in the combined studies. That's most likely because it's too soon to tell. Much longer follow-up is required before survival can be reliably measured.
Conclusions: In post-menopausal women with early-stage, hormone-receptor-positive breast cancer, women who switched to Arimidex for three years after taking tamoxifen for two years did better than those taking tamoxifen for five years. Switching reduced the risk of recurrence and the risk of developing a new cancer in the other breast.
Women who switched to Arimidex had fewer of the uncommon but serious side effects associated with tamoxifen: endometrial cancer, blood clots, and strokes. But women taking Arimidex had more joint aches and pains and bone fractures.
The researchers concluded that five years of tamoxifen is not the best treatment for post-menopausal women with early-stage, hormone-receptor-positive breast cancer. They recommended that women on tamoxifen be switched to Arimidex after two years of tamoxifen treatment.
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Arimidex After Two Years of Tamoxifen Reduces Recurrence in Post-Menopausal Women
This study showed an advantage for the women who switched to Arimidex for three years after taking tamoxifen for two years (for a treatment course of five years total), compared to women who stayed on tamoxifen for five years. The risk of recurrence and the risk of a new breast cancer were significantly less in the women who switched. So was the risk of serious side effects. The follow-up on this study, however, is still relatively short: two and a half years. With longer follow-up, we'll have more insights to share with women trying to make the best decisions.Here are some things to consider when deciding which hormonal therapy to take:
- Arimidex tends to cause fewer serious side effects than tamoxifen, including fewer cases of cancer in the uterus and fewer blood clots. It also causes fewer hot flashes. But much less is known about the long-term side effects of Arimidex compared to tamoxifen.
- Arimidex tends to cause more bone loss and more bone fractures than tamoxifen, at least for the first few years of treatment. Bone health is important in all women. Whether you decide to stay on tamoxifen or switch to an aromatase inhibitor, you should be careful about taking enough daily calcium and vitamin D, doing weight-bearing exercise, limiting alcoholic beverages, and staying away from tobacco use. If you decide to switch to Arimidex, you need to be even more mindful of your bone health. A DEXA scan (to test for bone density) before switching to an aromatase inhibitor can be quite helpful. If osteopenia or osteoporosis is detected, talk to your doctor about lifestyle changes, medications, and supplements that can build bone strength or prevent further bone loss.
- Tamoxifen is a generic drug and costs much less than the aromatase inhibitors, all of which are relatively new brands on the market. Aromatase inhibitors may cost between $200 and $300 a month, compared to $40 to $100 per month for tamoxifen. If you have serious financial concerns, or do not have insurance that will pay for an aromatase inhibitor, you can apply for financial assistance. Your local hospital may know about available funds. Or you can ask your doctor to submit a medication funding request to the pharmaceutical company that makes the aromatse inhibitor you're taking. If you'd like to contact the company directly, AstraZeneca's support center is called the Cancer Support Network, and the phone number is 866-992-9276. Pfizer's support center is called FirstRESOURCE, and the phone number is 877-744-5675. If funds are unavailable, staying on tamoxifen therapy is still a good option.
After a breast cancer diagnosis, it's a challenge to stay on top of all the decisions involved in your medical care. Which medicine is considered best today can change tomorrow. The treatment you started on should be re-evaluated over time in case a new and better treatment becomes available. Of course, it's important to think very carefully before changing treatments. Talk to your doctor about the best anti-estrogen medicine for YOU at this time. After you start treatment, you'll see your doctor regularly. At each visit you can go over what you like and don't like about your current treatment plan. Together, you can decide if you are going to stick to the current plan or consider switching to other options that might work better for you.