Nearly Half of Women Taking Tamoxifen for Primary Prevention Discontinue Its Use Before 5 Years

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After 4.5 years of taking tamoxifen for primary prevention of breast cancer, 46% of women discontinued its use, according to research conducted within the Sister Study, a prospective cohort of women who had a sister diagnosed with breast cancer but did not have breast cancer themselves. Eligible women were between the ages of 35 and 74 at enrollment. Researchers examined characteristics associated with initiating and discontinuing tamoxifen for primary prevention of breast cancer.

Tamoxifen has been approved by the U.S. Food and Drug Administration for primary prevention of breast cancer since 1998. “The U.S. Preventive Services Task Force (USPSTF) recently published a recommendation statement for risk reduction of primary breast cancer that encourages clinicians to offer to prescribe tamoxifen or raloxifene to reduce breast cancer risk,” Hazel B. Nichols, PhD, of the University of North Carolina Gillings School of Global Public Health, Chapel Hill, noted in the Journal of the National Cancer Institute.

“National estimates indicate that less than 1% of eligible women use tamoxifen for prevention. It is unknown why so few women use tamoxifen for breast cancer prevention, although vasomotor symptoms, increased risk of adverse health effects, and difficulties in estimating or communicating risk-benefit profiles can be deterrents.”

From 2003 to 2009, the Sister Study recruited 50,884 women in the United States and Puerto Rico. The current trial “identified 788 tamoxifen users and 3,131 nonusers matched on age and year of enrollment who had no history of contraindicating factors (stroke, transient ischemic attack, cataract, endometrial or uterine cancer),” the investigators stated. Study participants self-reported tamoxifen use, ages when they started and stopped taking tamoxifen, and total duration of its use at enrollment.

Women were categorized according to a risk-benefit index recommended by the USPSTF and the National Comprehensive Cancer Network (NCCN). “Briefly, the risk-benefit index classifies women according to the level of evidence (none, moderate, strong) for tamoxifen benefits (breast cancer and fracture prevention) to exceed the risk of serious side effects (endometrial cancer, stroke, pulmonary embolism, deep vein thrombosis, and cataract) using age, 5-year projected risk of invasive breast cancer, hysterectomy, and race,” the authors explained.

“Overall, 74% of classified tamoxifen users had a favorable (defined as moderate to strong evidence for benefits to exceed risks) risk-benefit profile, and 20% had no evidence that the benefits exceeded risks; the risk-benefit index could not be calculated for 6%,” the researchers reported. “Absence of expected benefit was most pronounced for older women, African Americans, and those with an intact uterus,” the authors added.

“Discontinuation of tamoxifen before the recommended 5 years (46%) was somewhat greater than the 24% to 36% nonadherence reported in prevention trials,” the authors acknowledged, but it “is closely aligned with a recent metaregression estimate of 47.2% 5-year discontinuation of tamoxifen as adjuvant endocrine therapy.”

The median duration of tamoxifen use among those who discontinued treatment was 3 years. “Raloxifene use after tamoxifen was associated with early discontinuation, potentially because of the availability of an alternative preventive therapy,” the researchers wrote. Women who reported a family history of breast cancer, BRCA1/2 testing, or positive mutation status appeared less likely to complete 5 years of tamoxifen.

The authors concluded: “While the majority of women who used tamoxifen for primary prevention of breast cancer were likely to benefit, substantial discontinuation of tamoxifen before 5 years and use by women at risk of serious side effects may attenuate benefits for breast cancer prevention.” ■

Nichols HB, et al: J Natl Cancer Inst 107:354, 2014 (print January 2015).