Five Years on Anastrozole Can Promote Progression to Osteoporosis

Paula Moyer, MA

June 12, 2006

June 12, 2006 (Atlanta) — Women with breast cancer who are treated with the aromatase inhibitor anastrozole (Arimidex, AstraZeneca) for 5 years can lose 6% to 7% in bone-mineral density (BMD), enough to trigger a progression to osteoporosis in those who are already osteopenic when treatment begins, according to a group of investigators that reported these findings here at the 42nd annual meeting of the American Society of Clinical Oncology.

For women with normal BMD at baseline, however, taking anastrozole for 5 years is unlikely to cause osteoporosis, said principal investigator Robert E. Coleman, MD, in a briefing. He presented these findings on behalf of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial investigators. Dr. Coleman is a professor of oncology at the University of Sheffield in the United Kingdom.

Women taking anastrozole also had about a 40% increased risk of fractures while on the study, he said, adding, "When the drug was discontinued, the excess fracture risk declined."

The ATAC trial recruited postmenopausal women with invasive primary breast cancer and randomized them to receive adjuvant treatment with Arimidex, tamoxifen, or combination therapy. According to previously reported trial results, Arimidex was superior to tamoxifen or combination therapy for preventing recurrence of breast cancer.

This 68-month subset analysis compared BMD between 81 women treated with Arimidex and 86 women treated with tamoxifen. Lumbar spine and total hip BMD were measured by dual-energy x-ray absorptiometry at baseline, 1 year, 2 years, and 5 years. At 5 years, women taking anastrozole lost 6.1% of BMD at the hip and 7.2% at the spine vs losses of 2.8% at the hip and 0.7% at the spine in the tamoxifen group (P < 0.0001).

The overall fracture rate was 7.7% among women taking tamoxifen in the study vs 11% for women taking anastrozole. Although Dr. Coleman stressed that the difference was significant, he did not report the P value. There was, he said, no statistically significant difference in the rate of hip fractures between women taking anastrozole and those taking tamoxifen.

The rate of loss decelerates over time; the rate at 2 to 5 years was significantly less than the loss over the first 2 years of treatment (mean difference in annual rate of change, 0.0113; 95% CI, 0.006 – 0.0017; P = 0.0002).

Five patients with osteopenia at baseline developed osteoporosis by the end of the follow-up period, he said.

On the basis of these results, Dr. Coleman recommended that women taking anastrozole have their BMD monitored every 1 to 2 years. "They should also take calcium and vitamin D supplements during anastrozole therapy," he said.

"It was interesting that women with a normal BMD at baseline did not develop osteoporosis," said Stephen Y. Chui, MD, who was not involved in the study. "This finding is reassuring for the first 5 years after a woman starts aromatase-inhibitor therapy, but we don't know what the long-term risks to bone health are after 5 years. Nonetheless, this observation regarding the safety of an aromatase inhibitor in women with normal baseline BMD is reassuring." Dr. Chui is an assistant professor of medicine at Oregon Health Sciences University in Portland, where he is an attending physician in the multidisciplinary breast cancer clinic.

"With our newer therapies, we will have more breast cancer survivors," he said. "These patients with normal baseline BMD may not require BMD monitoring as frequently as the annual recommendation. 

"There have been suggestions to start an aromatase inhibitor patient on bisphosphonates. Maybe that's not appropriate with lower risk factors. These findings may help us predict who needs intervention and who doesn't."

ASCO 42nd Annual Meeting: Abstract 511. Presented June 4, 2006.


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