When compared to tamoxifen, the benefits of anastrozole remain after women with hormone-sensitive breast cancer complete therapy, study shows
By Janine E. Guglielmino, LBBC Staff; reviewed by: Nancy U. Lin, MD
JF Forbes, et al. ATAC: 100 month median follow-up (FU) shows continued superior efficacy and no excess fracture risk for anastrozole (A) compared with tamoxifen (T) after treatment completion. Lancet Oncology 2008; Vol. 9: 45-53.
Anastrozole continues to work better than tamoxifen at preventing recurrences of hormone receptor-positive, early-stage breast cancer, even after postmenopausal women stop treatment, updated results of a clinical trial show.
After 100 months of follow-up, anastrozole (brand name: Arimidex) provided a 4.8 percent benefit over tamoxifen at protecting from recurrences overall and a 1.7 percent benefit over tamoxifen at preventing new cancers in the opposite breast. Women who took anastrozole had a higher risk of bone fractures during treatment than those who took tamoxifen, but the two groups had similar numbers once treatment was completed, regardless of type of hormonal therapy.
The updated data, presented at the 30th Annual San Antonio Breast Cancer Symposium in December 2007, comes from a long-term follow-up study of the Arimidex, Tamoxifen, Alone or in Combination, or ATAC, trial.
About the ATAC Trial
ATAC was a large international clinical trial that compared the effectiveness and safety of the aromatase inhibitor anastrozole to tamoxifen.
More than 9,000 postmenopausal women with early-stage, hormone receptor-positive breast cancer enrolled between 1996 and 2001. They were randomly assigned to receive one of three treatments for five years after finishing initial (adjuvant) treatment: anastrozole alone, tamoxifen alone or a combination of anastrozole and tamoxifen. The combination arm was discontinued early when preliminary results showed the two medicines together to be no more effective than tamoxifen alone.
After an average of nearly six years of follow-up, anastrozole worked better than tamoxifen at reducing the risk of breast cancer recurrence, researchers reported in January 2005 in the Lancet. Compared to participants who took tamoxifen, those on anastrozole also had fewer distant metastases and contralateral breast cancers (cancers in the opposite, or healthy, breast). Women taking anastrozole had fewer endometrial (uterine) cancers, a rare side effect of tamoxifen, but more bone fractures.
Based on ATAC and other large clinical studies, the American Society of Clinical Oncology recommended in late 2004 that aromatase inhibitors become the standard of care for postmenopausal women after treatment for estrogen receptor-positive, early-stage breast cancer, either in place of tamoxifen or after two to five years of tamoxifen.
Purpose of the Follow-Up Study
Some clinical trials are designed to follow participants for months, or even years, after researchers initially report findings. By allowing data to "mature," researchers learn more about the effectiveness of the study treatment over time, as well as its impact on side effects and quality of life after treatment ends.
In the follow-up study to ATAC, researchers continued monitoring participants after they completed five years of treatment with anastrozole and tamoxifen. They hoped to learn whether the benefits of anastrozole persisted after women stopped therapy. Also, researchers monitored side effects in both groups to see whether the incidence of bone fractures and endometrial cancer changed after treatment ended.
ATAC Study Results
After an average of 100 months, or eight and one-third years, women with ER positive cancers who took anastrozole were 4.8 percent less likely than those on tamoxifen to have had a recurrence, reported investigator John F. Forbes, MD, of the University of Newcastle in Australia. In the initial ATAC analysis, conducted after five years, the difference between the groups had been 2.8 percent in favor of anastrozole, suggesting the benefits of anastrozole grow over time.
The effectiveness of anastrozole versus tamoxifen at preventing breast cancer in the opposite breast also grew over time, from a negligible difference at 60 months to a 1.7 percent benefit in favor of anastrozole at 100 months.
Of the 6,241 women in this analysis, 624 who took tamoxifen passed away versus 629 on anastrozole. That means the two groups had similar rates of overall survival.
Anastrozole’s impact on bone health decreased between years five and eight. At year five, women who took anastrozole had 30 percent more bone fractures than those on tamoxifen. The 100-month analysis showed little difference between the groups, meaning the bones are most vulnerable to anastrozole’s effects during treatment.
Women who took tamoxifen continued to have higher rates of endometrial cancer than those on anastrozole, although the risk of endometrial cancer was low in both groups (.7 percent in the tamoxifen group versus .16 percent in the anastrozole group). The researchers discovered no new significant post-treatment side effects.
What the Findings Mean for You
If you take or plan to take aromatase inhibitors, these findings should help you feel confident that anastrozole will continue to provide superior protection against recurrences for several years after you finish treatment.
The findings reinforce the importance of protecting your bones during treatment. Talk with your doctor about lifestyle changes or medications that can help you sustain and build bone strength.
Read the abstract of the ATAC study of Arimidex and tamoxifen.