The effect of raloxifene on risk of breast cancer in postmenopausal women

Steven R. Cummings MD and others
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 1, 2001

Reviewers: Kenneth Blank, MD
Source: JAMA 1999 Jun 16; 281(23): 2189-97


The best treatment of cancer is prevention: simply put, if cancer does not occur it cannot cause morbidity or mortality. Towards this end investigators at several institutions have tested the ability of anti-estrogen medications, such as tamoxifen, to decrease the incidence of breast cancer. Two large trials recently published on this topic offered conflicting results.

In the June 16, 1999 issue of the Journal of the American Medical Association this issue is revisited. However, in place of tamoxifen, the investigators tested a new anti-estrogen medication: raloxifene. Raloxifene is classified as a selective estrogen receptor modulator and has properties distinct from tamoxifen. Both medications exert anti-estrogen effects on breast tissue but only raloxifene has pro-estrogen effects on bone, lipid metabolism and blood clotting. To determine whether raloxifene decreases the incidence of new cases of breast cancer, a multi-institutional trial called the MORE trial (Multiple Outcomes of Raloxifene Evaluation) started in the early 1990s.


Over 7,700 women were enrolled in this multi-national double-blind trial in which study participants were randomized to take raloxifene or placebo for three years. All women were post-menopausal and had a diagnosis of osteoporosis. Ninety six percent of women were white and none had a prior history of breast cancer. Raloxifene was dosed at 60mg tablets once or twice daily. Controls were similarly dosed with placebo tablets.


5,129 women received raloxifene and 2,576 women received placebo. The rate of new breast cancer was significantly less in the group receiving raloxifene. The practical interpretation of the relative risk of new breast cancer is to prevent one case of breast cancer, over 100 women need be treated with raloxifene. There was no increase in the risk of endometrial cancer in women taking raloxifene.

Raloxifene was generally well tolerated as evidenced by the fact that the same percentage of women completed the placebo and the raloxifene treatments (75% each). Side effects included hot flashes, flu-like symptoms, leg swelling and cramps. The risk of venous thrombosis and pulmonary embolism was significantly higher in the group taking raloxifene, and one woman died of a pulmonary embolism.


In the group of women under study (post- menopausal and white) raloxifene significantly decreased the risk of breast cancer. The risk of invasive breast cancer was decreased by 76% in women who completed three years of therapy. However, this benefit must be weighed against the increased risk of deep vein thrombosis and pulmonary embolus.