NEW YORK (Reuters Health) – Findings from a systematic review indicate that while tamoxifen, raloxifene, and tibolone all reduce the risk of primary breast cancer, the drugs differ in their side effects.

According to the report in the Annals of Internal Medicine for September 15, tamoxifen and raloxifene increase the risk of thromboembolic events, tamoxifen ups the risk of endometrial cancer, and tibolone raises the risk of stroke. Still, the absolute risks of these events are small and, for many women, the pros of taking these agents are likely to outweigh the cons, the report indicates.

To examine the benefits and harms of the three drugs, Dr. Heidi D. Nelson, from Oregon Health and Science University, Portland, and colleagues searched MEDLINE and Cochrane databases through January 2009 for relevant studies.

Randomized controlled trials were included for benefit analysis, while both trials and observational studies were included for harm analysis. Ultimately, seven placebo-controlled trials and one head-to-head trial were included in the main outcomes analysis. The trials were large, ranging from more than 2,000 subjects to more than 19,000, and most had treatment durations of at least 4 years.

As noted, all three drugs were effective in reducing the risk of invasive breast cancer. Relative to placebo, tamoxifen, raloxifene, and tibolone reduced the risk by 30%, 56%, and 68%, respectively. This equates to 7 to 10 fewer cases of breast cancer per 1000 women per year.

Further analysis showed that the beneficial effects of tamoxifen and raloxifene were limited to estrogen receptor-positive breast cancer. All three drugs reduced the risk of fractures.

Compared with placebo, tamoxifen and raloxifene increased the odds of thromboembolic events by 93% and 60%, respectively, which equates to 4 to 7 extra cases per 1000 women per year. Tamoxifen was also linked to a 2.13-fold elevated risk of endometrial cancer, which yields an extra 4 cases of the malignancy per 1000 women per year. Tibolone was found to increase the risk of strokes, particularly in women over 70 years.

“Before applying these findings to practice, clinicians must assure that women understand their individual risks for breast cancer and can favorably balance these with the unwanted effects of risk reducing medications,” Dr. Nelson’s team emphasizes.

Reference:
Ann Intern Med 2009.