Tamoxifen and raloxifene reduce the incidence of invasive breast cancer in women without cancer, according to an analysis of several large controlled trials. However, they also increase the risk of blood clots and other risks.
“Tamoxifen was more effective than raloxifene in reducing breast cancer but also increased the incidence of endometrial cancer and cataracts. Both medications reduced fractures. Adverse effects were more common in older compared to younger women,” lead author Heidi D. Nelson, MD, MPH, Research Professor, Medical Informatics and Clinical Epidemiology and Medicine, Oregon Health and Science University, Portland, told ConsultantLive.
Widespread use of these medications is limited by their adverse effects and inaccurate methods to identify candidates, Dr Nelson said. “Many women do not take tamoxifen because of associated harms,” she noted. “We evaluated 13 risk stratification models that showed only a modest ability to predict breast cancer for individuals.”
Dr Nelson and colleagues at the Pacific Northwest Evidence-based Practice Center conducted a systematic review for the US Preventive Services Task Force (USPSTF).
This report is an update of the 2002 USPSTF report that was derived from a comprehensive comparative effectiveness review of the efficacy, adverse effects, and subgroup variations of medications to reduce the risk of primary breast cancer in women.
The current review focused on randomized clinical trials of tamoxifen and raloxifene compared with placebo, and 1 trial of tamoxifen compared directly with raloxifene. Raloxifene may be used only in postmenopausal women; tamoxifen may be used at any age, Dr Nelson noted.
The investigators also evaluated how well methods to identify women at increased risk for breast cancer actually predict cancer. They did not include trials of other, non–FDA-approved medications that are used for risk reduction.
Women enrolled in the tamoxifen trials were younger than women in the raloxifene trials (47 to 50 years vs 67 years) and met specific risk criteria (US studies used Gail score 1.67% or greater risk for breast cancer in the next 5 years).
Results of 4 placebo-controlled trials of tamoxifen and 2 of raloxifene were statistically combined to obtain summary outcome measures.
“The medications reduced invasive breast cancer by 7 to 9 cases per 1000 women, assuming 5-years of use,” Dr Nelson said. There are 5 per 1000 fewer cases among women using tamoxifen than raloxifene. Estrogen receptor–positive breast cancers were reduced, but not estrogen receptor–negative ones.
Risk reduction was greatest among women with previous atypical hyperplasia and with estimated 5-year risks greater than 5%. Tamoxifen reduced non-spine fractures by 3 per 1000, and raloxifene reduced spine fractures by 7 per 1000.
Both medications increased blood clots by 4 to 7 cases per 1000 women; tamoxifen caused 4 per 1000 more than raloxifene.
The USPSTF issued a draft statement recommending that physicians engage women at increased risk for breast cancer in shared decision making about medications that can reduce their risk. The USPSTF also encouraged physicians to offer to prescribe medications, such as tamoxifen or raloxifene, to these higher-risk women. The Task Force recommended against routine use of these medications in women who are not at increased risk for breast cancer.
The researchers reported their results on April 16 in the Annals of Internal Medicine.
New York Times, “Breast Cancer Drugs Urged for Healthy High-Risk Women”
DailyRx.com, “Medicine Before Breast Cancer Strikes”