Drugs effective in reducing breast cancer risk but increase Risk of Adverse Effects, says new US govt report

Three drugs, including tamoxifen, reduce a woman's chance of getting breast cancer, but each one carries distinct potential harms of its own, according to a new report from the US Department of Health and Human Services' Agency for Healthcare Research and Quality.

Drugs to reduce the risk of breast cancer can be prescribed to women with a family history of breast cancer or other risk factors, but prescribing practices vary widely. The comparative effectiveness review found that all three drugs - tamoxifen, raloxifene, and tibolone - significantly reduce invasive breast cancer in midlife and older women but that benefits and adverse effects can vary depending on the drug and the patient.

"Taking medicine to avoid breast cancer in the first place is an attractive notion, but the decision to do so must be made by patients in consultation with their clinicians with benefit of the best evidence available," said AHRQ Director Carolyn M. Clancy. "These drugs are not necessarily for everyone. This report sheds important light on their advantages and potential harms," she added.

The report is the first to make a direct, comprehensive comparison of the drugs so that women and their health care providers can assess the medications' potential effectiveness and adverse effects. The report compares the use of the three drugs to reduce the risks of getting breast cancer in women who have not previously had breast cancer.

Breast cancer is the second most commonly diagnosed cancer of women (after skin cancer), with more than 190,000 new cases diagnosed each year in the USA. It is estimated to cause more than 40,000 deaths per year. The National Cancer Institute estimates that nearly 1% of women born today will develop breast cancer in their lifetimes. Most cases of breast cancer occur in women with no specific risk factors other than age and gender, although family history of breast and ovarian cancer is associated with higher risk.

Tamoxifen, a selective estrogen receptor modulator (SERM), was approved by the US Food and Drug Administration in 1998 to prevent breast cancer in women at high risk of developing the disease. Tamoxifen's use to reduce the risk of breast cancer is accepted clinical practice, although the drug is primarily used for treatment rather than risk reduction.

The AHRQ report compared tamoxifen with another SERM, raloxifene, which is primarily used to prevent and treat osteoporosis and was approved by the FDA for breast cancer risk reduction in 2007. A third drug, tibolone, which has not been approved by the FDA for use in the USA but is commonly used in other countries to treat menopausal symptoms and osteoporosis, also was included in the study.

The report found that all three drugs reduce the occurrence of breast cancer but have various side effects. The most common side effects for tamoxifen are flushing and other vasomotor symptoms (eg, night sweats, hot flashes), vaginal discharge and other vaginal symptoms such as itching or dryness; for raloxifene, side effects include vasomotor symptoms and leg cramps; and for tibolone, side effects include vaginal bleeding.

The report also found that each drug carried the risk of adverse effects. It found that tamoxifen increases risk for endometrial cancer, hysterectomies and cataracts compared with the other drugs. Tamoxifen and raloxifene increase risk of blood clots, although tamoxifen's risk is greater. Tibolone carries an increased risk of stroke.

Additionally, the report examined the drugs' effectiveness and harms based on such factors as age, menopausal status, estrogen use and family history of breast cancer and sought to identify the kinds of women who might be good candidates for prevention therapy, although the evidence is limited in this area. The report called for more research to more clearly identify characteristics of patients who would benefit from these drugs while suffering the least harm.

The AHRQ's new report, Comparative Effectiveness of Medications to Reduce Risk of Primary Breast Cancer in Women, is the latest analysis from the Agency's Effective Health Care Program. That program, authorized by the Medicare Prescription Drug Improvement and Modernization Act of 2003, represents an important federal effort to compare alternative treatments for health conditions and make the findings public. The program is intended to help patients, doctors, nurses, and others choose the most effective treatments. Information, including the new report, can be found at www.effectivehealthcare.ahrq.gov.