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Tamoxifen - managing adverse effects - Evidence
Evidence on adverse effects of tamoxifen
CKS found two large trials which suggested that tamoxifen increases the risk of endometrial cancer and thromboembolic events, although the absolute numbers are small.
- The Breast Cancer Prevention Trial (P-1) from the National Surgical Adjuvant Breast and Bowel Project was a randomized controlled trial that studied 13,388 women at increased risk for breast cancer and assigned them to receive placebo (n = 6707) or tamoxifen 20 mg daily (n = 6681) for 5 years [Fisher et al, 1998].
- Endometrial cancer: the risk of developing endometrial cancer was 2.53 (95% CI 1.35 to 4.97) times greater in the tamoxifen group (2.3/1000 participants/year) than in the placebo group (0.91/1000 participants/year). However, the increased risk was mainly in women 50 years of age or older.
- Stroke: the incidence increased from 0.92/1000 participants/year in the placebo group to 1.45/1000 participants/year in the tamoxifen group, with a relative risk of 1.59. However, these results were not statistically significant.
- Pulmonary emboli: a total of 18 women in the tamoxifen group and 6 women in the placebo group developed pulmonary embolism (RR 3.01; 95% CI 1.15 to 9.27).
- Deep vein thrombosis: a total of 35 women in the tamoxifen group and 22 women in the placebo group developed deep vein thrombosis (RR 1.60; 95% CI 0.91 to 2.86).
- The International Breast Cancer Intervention Study (IBIS-I) was a double-blind, placebo-controlled, randomized trial of tamoxifen 20 mg daily for 5 years which included 7152 women (3578 in the tamoxifen group and 3566 in the placebo group) [Cuzick et al, 2002].
- Endometrial cancer: eleven women in the tamoxifen group, compared with five women in the placebo group, developed endometrial cancer. The odds ratio was 2.2, but this was not significant (95% CI 0.80 to 6.06, p = 0.2).
- Venous thromboembolic events: the rate was 2.5 times higher in the tamoxifen group compared with the placebo group. Forty-three women in the tamoxifen group had venous thromboembolic events compared with 17 women in the placebo group (95% CI 1.5 to 4.4, p = 0.001).
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