Anastrozole Prevents Relapse in Early Breast Cancer: Results of the ATAC TrialKey Words
Breast cancer, anastrozole (Arimidex®), tamoxifen (Nolvadex®), relapse, aromatase inhibitors, ATAC trial. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Summary
Anastrozole (Arimidex) was significantly better than tamoxifen (Nolvadex) - or the combination of tamoxifen and anastrozole - at preventing a recurrence of breast cancer in postmenopausal women whose early-stage tumors were hormone-sensitive, according to the final results of ATAC, a large international clinical trial. Patients on anastrozole also experienced fewer side effects. Anastrozole is now considered a standard adjuvant (additional) treatment option for this group of patients.
Source
The Lancet, January 1, 2005 (see the journal abstract).
Background
Postmenopausal women who have been treated for early breast cancer and whose tumors are “hormone sensitive” (that is, the tumors grow in response to the hormones estrogen and progesterone) have been advised to take the anti-estrogen drug tamoxifen for five years. Such
adjuvant treatment has been shown to help prevent a relapse and has been considered the standard of care for this group of patients.
However, women taking tamoxifen are at an increased risk for endometrial cancer and blood clot disorders. Other studies have suggested that a different class of drugs called aromatase inhibitors (AIs) might prove a better alternative.
Like tamoxifen, AIs interfere with cancer cells’ use of hormones but in a different way. Tamoxifen interferes directly with the cancer cells’ ability to use estrogen for fuel, while AIs block the action of a substance called aromatase, which helps the body produce estrogen. Anastrozole is an aromatase inhibitor.
Studies of various AIs have been promising, but the drugs’ long-term effects are unknown. In November 2004, the American Society of Clinical Oncology recommended that postmenopausal women with hormone-sensitive breast cancer consider one of two adjuvant treatment options:
- begin treatment with tamoxifen for two-to-five years, then switch to an AI for another two-to-five years, or
- forego tamoxifen entirely and begin adjuvant treatment with an AI for five years.
The final, five-year results from the Arimidex, Tamoxifen Alone or in Combination (ATAC) study, described here, are the first long-term results about an AI used as an adjuvant treatment for early breast cancer.
The Study
The ATAC study is a double-blinded phase III clinical trial. The study enrolled 9,366 postmenopausal women with localized breast cancer (that is, the cancer hadn’t spread or metastasized). The women were randomly assigned to receive either anastrozole alone, tamoxifen alone, or a combination of the two. The research team was led by Anthony Howell, M.D., of Christie Hospital NHS Trust in Manchester, United Kingdom.
In December 2001, after 33 months of study, ATAC researchers announced early results showing that women taking anastrozole were less likely - by 17 percent - to suffer a relapse, compared to women taking tamoxifen. However, the results were considered too preliminary to justify a recommendation that this patient group take anastrozole instead of tamoxifen after their initial breast cancer treatment.
Now, however, ATAC researchers have announced the results from five years of data, which suggest that anastrozole should perhaps be the preferred adjuvant treatment.
Results
After a median follow-up period of five years and eight months, women taking anastrozole in the ATAC study were significantly better off than those taking tamoxifen. Compared to tamoxifen, anastrozole increased disease-free survival by 10 percent; increased time to relapse by about 20 percent; reduced the occurrence of cancer spreading to other organs (distant metastases) by 14 percent, and reduced the occurrence of cancer in the other breast by more than 40 percent.
In addition, women taking anastrozole were more likely to make it through their scheduled treatment than were women taking tamoxifen - anastrozole was associated with fewer serious side effects (endometrial cancer, blood clots, vaginal bleeding, hot flashes), though bone fractures and joint pain were more common in the anastrozole group. The incidence of hip fracture was low and was similar in both groups.
Note: A substudy of the ATAC trial concerning bone loss appeared in the March 1, 2008, Journal of Clinical Oncology; see the related story.
Limitations
These results are valid only for anastrozole. It remains to be seen whether initiating therapy with other AIs (such as letrozole and exemestane) work similarly well at preventing breast cancer relapse. In addition, the optimal timing and duration of the aromatase inhibitors is not known.
Comments
“This study provides strong evidence that anastrozole is both safe and effective in the treatment of postmenopausal women with early stage breast cancer. Other studies using different aromatase inhibitors in early stage breast cancer further support these findings,” says JoAnne Zujewski, M.D., of the National Cancer Institute’s Cancer Therapy Evaluation Program.
“Whether an individual patient should start therapy with an aromatase inhibitor or begin therapy with tamoxifen and then change to an aromatase inhibitor is a subject of medical judgment and clinical research,” she adds. “Patients should talk with their doctors about which drug would be best for them given their particular medical condition.”
Note: In the August 2006 issue of the Lancet Oncology (see the journal abstract), researchers with the ATAC trial report data after an extended follow-up period showing that anastrozole was tolerated better than tamoxifen and resulted in fewer serious complications. Furthermore, anastrozole had a more favorable overall risk-benefit profile and a lower recurrence rate than tamoxifen. Results after 100 months of follow-up were reported in the January 2008 Lancet Oncology (see the journal abstract).
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