Draft recommendations being considered by the U.S. Preventive Services Task Force encourage clinicians to offer tamoxifen or raloxifene to women who have an increased risk of developing a first breast cancer and a low risk of side effects.
The document reaffirms 2002 recommendations from the Task Force with updated evidence on the risks and benefits of this prophylactic strategy and somewhat stronger wording, saying clinicians should "offer to prescribe" the drugs to appropriate candidates rather than simply "discuss" this option and "inform" patients of the risks and benefits.
Dr. Heidi Nelson
The Task Force is accepting online comments about its draft until May 13 before finalizing its recommendations.
The draft document was informed by a systematic review of the literature that suggests tamoxifen or raloxifene can reduce the incidence of invasive breast cancer in higher-risk women by 7-9 cases per 100,000 women over 5 years, compared with placebo. The review by Dr. Heidi D. Nelson and her associates was published online in advance of print by the Task Force and by the Annals of Internal Medicine (Ann. Intern. Med. 2013;158:604-14). The incidence of breast cancer was lower with tamoxifen in a head-to-head trial, the Study of Tamoxifen and Raloxifene (STAR), with 5 fewer cases per 1,000 women on tamoxifen compared with raloxifene.
The drugs also reduce the incidence of fracture, with 7 fewer vertebral fractures per 1,000 women on raloxifene or 3 fewer nonvertebral fractures per 1,000 women on tamoxifen, the literature suggests.
Neither drug reduced deaths from breast cancer or deaths from any cause in the published studies, reported Dr. Nelson, a research professor in the departments of medical informatics and clinical epidemiology and medicine at Oregon Health and Sciences University, Portland. Data were lacking on use of these drugs by nonwhite, premenopausal, or elderly women who have comorbid conditions or are taking other medications
Because both of these selective estrogen receptor modulator drugs have potentially serious side effects, the Task Force recommended in both its 2002 guidelines and the 2013 draft that they not be used by women who are not at increased risk for breast cancer. In higher-risk women, both drugs increase the risk of thromboembolic events. Studies have associated tamoxifen with 4 extra thromboembolic events per 1,000 women and raloxifene with 7 excess events per 1,000 women. Tamoxifen use was associated with 4 extra endometrial cancers compared with placebo and increased the risk for ischemic stroke and cataracts. Both drugs can cause less serious side effects, most commonly vasomotor symptoms (hot flashes).
Few U.S. women use tamoxifen or raloxifene to prevent primary breast cancer, in part because it is not clear how to indentify candidates for this therapy, according to Dr. Nelson’s report. Models estimate that women with at least a 3% risk of developing breast cancer in the next 5 years are more likely to benefit than be harmed from tamoxifen or raloxifene, the Task Force draft states. The recommendations would apply to asymptomatic women aged 40-70 years with no history of breast cancer, ductal carcinoma in situ, lobular carcinoma in situ, or thromboembolic events.
An online risk assessment tool from the National Cancer Institute that is based on the Gail model of risk assessment can help estimate a person’s 5-year risk of invasive breast cancer, one of 13 risk-stratification models examined in the medical literature. Most models performed only slightly better than use of age alone to predict risk, Dr. Nelson reported. The Food and Drug Administration approved use of tamoxifen or raloxifene to prevent breast cancer if the 5-year risk is at least 1.67% under the Gail model, but women aged 60 years or older who had no other risk factors would meet this threshold using age alone, her review found.
Data are lacking on the optimal doses, and the duration and timing of therapy. The typical doses used to reduce invasive breast cancer risk in several randomized trials are 20 mg/day of tamoxifen or 60 mg/day of raloxifene for 5 years.
The Task Force draft deals only with tamoxifen and raloxifene because these are the only two drugs approved by the FDA to reduce the risk of hormone receptor–positive breast cancer. The draft recommendations note, however, that more data should be coming from trials of possible drug candidates such as aromatase inhibitors. Dr. Nelson’s review notes that tibolone, lasofoxifene, and exemestane reduced breast cancer risk in some trials and "may expand clinical options."
The American Cancer Society in 2013 urged women who are considering chemoprevention for breast cancer to discuss the risks and benefits with their physicians. A 2009 clinical practice guideline update by the American Society of Clinical Oncology said tamoxifen may be offered to women at increased risk of breast cancer and raloxifene may be offered to postmenopausal women at increased risk (J. Clin. Oncol. 2009;27:3235-58).