Source: Kardiologiia  |  Posted 7 years ago

By Paula Moyer

HAMBURG, GERMANY -- March 22, 2004 -- Loss of bone-mineral density (BMD) related to treatment with anastrozole (Arimidex) is typical of the aromatase inhibitor class, but the process does stabilise over time, noted researchers during a presentation here March 18th at the 4th European Breast Cancer Conference.

In a recent randomised, double blind trial known as Anastrozole, Tamoxifen, and Combination (ATAC), researchers compared all adverse effects of anastrozole compared with those of tamoxifen in 9,366 postmenopausal women with early breast cancer and found that anastrozole was better tolerated, said Robert E. Coleman, MBBS, MD, FRCP, Professor of Medical Oncology, Cancer Research Centre, Weston Park Hospital, Sheffield, United Kingdom.

Dr. Coleman presented the findings of a second study that extrapolates data from ATAC. He said his team was motivated because of the known BMD-depleting effects of low oestradiol levels in women, and because aromatase inhibitors are known to further reduce oestrogen levels in postmenopausal women.

"Anastrozole is the only aromatase inhibitor with published data analysing its impact on BMD in postmenopausal women with early breast cancer," said Dr. Coleman. In the ATAC trial, patients were randomised to receive 1 mg daily of anastrozole, 20 mg daily of tamoxifen, or a combination of the 2 drugs, and the investigators assessed the fracture incidence every 6 months for up to 48 months of treatment.

In the current study, Dr. Coleman reported the BMD results after 2 years of therapy, and included fracture rates over time. The investigators extrapolated a subset of 308 women from the trial who were measured by dual energy X-ray absorptiometry (DXA) at 2 locations: the lumbar spine and total hip.

The BMD statistical assessment utilised ANOVA on log-transformed data (95% confidence interval), and compared baseline lumbar-spine and total-hip BMD with the BMD in those sites after 1 and 2 years of therapy.

At those time points, anastrozole was associated with bone loss at the spine of 2.6% and 4.0% at 1 and 2 years; bone loss at the hip was 1.7% and 3.2% at those time points, respectively. During that time period, tamoxifen was associated with an increase in BMD, so that at the spine the average BMD gain was 1.2% at 1 year and 1.9% at 2 years; at the hip those increases were 0.8% and 1.2% at those time periods, respectively.

The rate of anastrozole-associated bone loss was relatively constant over those years, Dr. Coleman said, noting that the changes in BMD between the tamoxifen and combination groups were not significantly different, and that the T-score changes between these groups also did not change significantly.

At 2 years, the median T-score change from the baseline in the anastrozole group was -0.36 at the lumbar spine, and -0.30 at the hip. In the tamoxifen group at that time the T scores change was a median of +0.18 at the lumbar spine and +0.09 at the hip. In the combination group, the T scores change was a median of +0.11 at the lumbar spine and +0.06 at the hip.

When patients had undergone treatment for a median of 31 months, the fracture incidence was 5.9% for the anastrozole group and 3.7% for the tamoxifen group. The investigators' analysis showed that the anastrozole patients had a relative risk of fracture of 1.59 compared to the tamoxifen group. Following a safety update when the median duration of therapy was 37 months, the anastrozole group's relative risk for fracture was 1.60.

The semi-annual fracture rates remained relatively stable for both the anastrozole and tamoxifen groups, Dr. Coleman reported, so that, after 24 months, the 6-monthly fracture rates seen with anastrozole did not appear to increase over time with further treatment.

Dr. Coleman added that, although solutions need to be found to protect women who are treated with aromatase inhibitors from BMD loss and the risk of fracture, this aspect of anastrozole must be considered in the context of other risks associated with tamoxifen, such as thrombosis and endometrial cancer.

"Given the efficacy and numerous tolerability benefits of the 2 [drugs], the overall risk-benefit favours anastrozole in early breast cancer therapy," he said.

[Study Title: Effect of Anastrozole on Bone Mineral Density and Bone Fractures: Results From the Arimidex (Anastrozole), Tamoxifen, Alone or in Combination (ATAC) Trial. Abstract 289]