Tamoxifen and raloxifene are approved by the FDA for use in preventing breast cancer in women at high risk of the disease, which is typically defined as a 1.67 percent chance or greater of developing breast cancer over a five year period. Tamoxifen is approved for women age 35 and older, while raloxifene is approved for post-menopausal women. Since the risk of the disease goes up with age, a 1.67 percent risk essentially translates to the 5-year risk of an average woman 60 years old or over. (To see where your risk falls, visit the National Cancer Institute Breast Cancer Risk Assessment Tool.) This means approximately 10 million women in the United States are eligible for using these medications for prevention.
Yet, their current use is astonishingly low, especially given that breast cancer is a disease so feared by many women and that the medications have been demonstrated in clinical trials of high-risk women to cut the long term risk of breast cancer by 50 percent.
A recent study by Erika Waters and colleagues found that only about 117,000 women (well under one percent) in eligible age groups were taking either tamoxifen or raloxifene - a number that has basically remained steady since the year 2000.
So what keeps more women from taking these risk-reducing medications? Evidence shows that it's the potential risk of side effects that likely sways eligible patients away from using - and their doctors from prescribing - tamoxifen or raloxifene. Side effects, of course, are an important consideration when deciding whether or not to take any medication, and potential harms of tamoxifen and raloxifene, while rare, can be serious - including, stroke, blood clots, and uterine cancer. So, it's good that many women approach them with caution.
Yet, simply knowing the side effects of these drugs isn't enough to provide a full picture of their ability to help or harm women. It's important to know the likelihood that a woman might experience side effects and to put this into context with the potential breast health benefits. It is here where it can be hard for patients - and even their doctors - to properly balance the harms and benefits of these drugs and decide when the benefits are likely to outweigh the harms.
It certainly makes sense that no woman wants to trade one serious risk for another - lowering, say, breast cancer risk but upping stroke or endometrial cancer risk an equal amount. But, reviews of evidence show that there are some pretty clear groups of women for whom the benefits of tamoxifen or raloxifene outweigh the potential harms.
The draft Task Force recommendation states that, overall, the benefits of risk-reducing medications start to outweigh the harms when the 5-year risk of breast cancer hits 3 percent or greater. Based on the same evidence, National Cancer Institute researchers have described in detail in women age 50 and older which groups of women are likely to benefit from risk-reducing medication based on age, race, risk level, and whether or not a woman has had her uterus removed. In general, the younger a woman is and the higher her risk, the more likely the benefit from taking risk-reducing medications will outweigh the potential harms.
The tables below show the 5-year risk for different groups where the risk-lowering benefits of tamoxifen or raloxifene are likely to outweigh the harms. Because tamoxifen can raise the risk of uterine cancer - and raloxifene does not - raloxifene is recommended over tamoxifen in women over 50 who still have a uterus. For women without a uterus, the potential harms and benefits of tamoxifen and raloxifene are similar.
That so many women at increased risk of breast cancer choose not to take tamoxifen and raloxifene is a health paradox. "In many stories of medical advancements, it's the risks that frequently get hidden in the news headlines, but with tamoxifen and raloxifene, it seems it's just the opposite," says Graham Colditz, MD, DrPH, a Professor of Surgery at Washington University School of Medicine and Associate Director of Prevention and Control at the Siteman Cancer Center. "The harms seem to get over-played in relation to the benefits. This leaves many women and their doctors passing up what science shows is a great chance to halve their risk of breast cancer. It's a huge opportunity missed."
Freedman AN, Graubard BI, Rao SR, McCaskill-Stevens W, Ballard-Barbash R, Gail MH. Estimates of the number of US women who could benefit from tamoxifen for breast cancer chemoprevention. J Natl Cancer Inst. 2003;95(7):526-32.
Freedman AN, Yu B, Gail MH, Costantino JP, Graubard BI, Vogel VG, et al. Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older. J Clin Oncol. 2011;29(17):2327-33. PMCID: 3107748.
Waters EA, McNeel TS, Stevens WM, Freedman AN. Use of tamoxifen and raloxifene for breast cancer chemoprevention in 2010. Breast Cancer Res Treat. 2012;134(2):875-80.