Risk-benefit profiles of women using tamoxifen for chemoprevention

Abstract

Background: Tamoxifen has been US Food and Drug Administration-approved for primary prevention of breast cancer since 1998 but has not been widely adopted, in part because of increased risk of serious side effects. Little is known about the risk-benefit profiles of women who use chemoprevention outside of a clinical trial. We examined characteristics associated with initiation and discontinuation of tamoxifen for primary prevention of breast cancer within a large cohort of women with a first-degree family history of breast cancer.

Methods: This research was conducted within The Sister Study, a cohort of 50884 US and Puerto Rican women age 35 to 74 years enrolled from 2003 to 2009. Eligible women were breast cancer-free at enrollment and had a sister who had been diagnosed with breast cancer. Participants reported tamoxifen use, ages started and stopped taking tamoxifen, and total duration of use at enrollment. We identified 788 tamoxifen users and 3131 nonusers matched on age and year of enrollment who had no history of contraindicating factors (stroke, transient ischemic attack, cataract, endometrial or uterine cancer). Characteristics associated with tamoxifen initiation were evaluated with multivariable conditional logistic regression. All statistical tests were two-sided.

Results: Based on published risk-benefit indices, 20% of women who used tamoxifen had insufficient evidence that the benefits of tamoxifen outweigh the risk of serious side effects. After 4.5 years, 46% of women had discontinued tamoxifen.

Conclusions: While the majority of women who used tamoxifen for primary prevention of breast cancer were likely to benefit, substantial discontinuation of tamoxifen before five years and use by women at risk of serious side effects may attenuate benefits for breast cancer prevention.

Figure 1.

A) Percent of tamoxifen users with a risk-benefit index (16,20) indicating no, moderate, or strong evidence that the benefits of tamoxifen for the primary prevention of breast cancer and fracture exceed the risk of serious side effects (ie, endometrial cancer, stroke, pulmonary embolism, deep vein thrombosis, and cataract). Percentages are shown overall and according to hysterectomy status, race, and age at tamoxifen initiation. B) Odds ratios (95% confidence intervals) for a favorable risk-benefit profile (moderate or strong evidence that benefits of tamoxifen outweigh the risks) according to hysterectomy status, race, and age at tamoxifen initiation. CI = confidence interval.

Figure 2.

Kaplan–Meier survival curve of discontinuation before five years among women taking tamoxifen for primary prevention of breast cancer.