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Almost Half of Women Taking Tamoxifen for Primary Prevention of Breast Cancer Discontinue Use Before 5 Years

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Key Points

  • After 4.5 years of taking tamoxifen for primary prevention of breast cancer, 46% of women discontinued use, according to research among women who had a sister diagnosed with breast cancer but did not have breast cancer themselves.
  • 74% of the tamoxifen users had a favorable risk-benefit profile, but 20% had no evidence that the benefits exceeded risks.
  • Women reporting a family history of breast cancer, BRCA1/2 testing, or positive mutation status appeared less likely to complete 5 years of tamoxifen.

After 4.5 years of taking tamoxifen for primary prevention of breast cancer, 46% of women discontinued use, according to research conducted within the Sister Study, a prospective cohort of women who had a sister who had been diagnosed with breast cancer but did not have breast cancer themselves. The findings were reported by Nichols et al in the Journal of the National Cancer Institute.

Tamoxifen has been approved by U.S. Food and Drug Administration (FDA) 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,” the investigators 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 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.”

Most Had Favorable Risk-Benefit Ratio

From 2003 to 2009, the Sister Study recruited 50,884 women in the United States and Puerto Rico to examine characteristics associated with initiating and discontinuing tamoxifen for primary prevention of breast cancer. The trial included 788 tamoxifen and 3,131 nonusers matched for age and year of enrollment who had no history of contraindicating factors, Study participants self-reported tamoxifen use, ages when they started and stopped taking tamoxifen, and total duration of 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,” they added.

May Attenuate Benefits for Prevention.

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

The median duration of use among those who discontinued was 3 years. Factors associated with early discontinuation of therapy included family history of breast cancer, BRCA1/2 testing, positive mutation status, and raloxifene use after tamoxifen, which the researchers suggested could be due to the availability of an alternative preventive therapy.

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.”

Hazel B. Nichols, PhD, of the University of North Carolina Gillings School of Global Public Health, Chapel Hill, is the corresponding author for the Journal of the National Cancer Institute article.

The study was supported by the Intramural Research Program of the National Institutes of Health, the National Institutes of Environmental Health Sciences, and the National Center of Advancing Translational Sciences.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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