Although most women who use tamoxifen for breast cancer prevention will derive benefit, more attention must be paid to the risk–benefit profiles of certain subgroups of at-risk women who may be more likely to experience serious side effects, according to study results.
These subgroups include older women, black women and women who have an intact uterus.
Tamoxifen — which received FDA approval in 1998 for primary prevention of breast cancer for women who meet specific age and risk criteria — is not widely used, primarily due to an increased risk for serious adverse effects. Less than 1% of eligible women in the United States use tamoxifen for prevention of breast cancer, according to study background.
Hazel B. Nichols
Hazel B. Nichols, PhD, assistant professor in the department of epidemiology at the University of North Carolina Gillings School of Global Public Health, and colleagues assessed tamoxifen use among women enrolled in The Sister Study, a prospective cohort of more than 50,000 American and Puerto Rican women (age range, 35 to 74 years) recruited between 2003 and 2009 to assess genetic and environmental risk factors for breast cancer. All women were breast cancer-free at the time of enrollment and had a sister who had been diagnosed with breast cancer.
Nichols and colleagues initially identified 1,046 women from the cohort (2.1%) who used tamoxifen.
After exclusions for contraindicating medial conditions, participation in a tamoxifen clinical trial or diagnosis of lobular carcinoma in situ, researchers limited their analysis to 788 tamoxifen users. More than 90% of the tamoxifen users were non-Hispanic white.
Researchers compared these women with 3,131 nonusers of tamoxifen who were matched for age, year of enrollment, and no history of contraindicating factors.
The researchers examined risk–benefit profiles of women who used tamoxifen for breast cancer prevention, as well as the characteristics associated with the initiation of the agent and its eventual discontinuation.
The researchers categorized the women using a risk–benefit index that classified them according to the level of evidence for tamoxifen benefit (none, moderate or strong) to exceed the risk for serious adverse effects, which included stroke, pulmonary embolism, deep vein thrombosis, endometrial cancer and cataract. The indices accounted for age, race, hysterectomy status and 5-year projected risk for invasive breast cancer.
The mean age of the tamoxifen users at the time of initiation was 50.7 years. Overall, 74% of tamoxifen users demonstrated either a moderate or strong benefit. An additional 20% of women showed no indication that benefit outweighed risk. Researchers were unable to calculate a risk–benefit index for the remaining 6%.
Net benefits varied between different groups.
Women who had hysterectomies performed before tamoxifen initiation were 11 times more likely to have a favorable risk–benefit profile than women with an intact uterus (OR = 11.87; 95% CI, 5.94-23.73).
Younger women showed a significant benefit from tamoxifen, as 99.1% of the women who started tamoxifen before age 50 years showed a moderate or strong benefit.
Black women were 65% less likely to derive a benefit than non-Hispanic white women (OR = 0.35; 95% CI, 0.16-0.75).
“We have seen that not all women who take tamoxifen for chemoprevention will have equivalent evidence that the risks outweigh the benefits,” Nichols said in a press release. “But the risk–benefit tool is easy to apply to estimate whether a woman’s benefits are likely to outweigh the risks.”
Families with extensive histories of breast cancer or higher breast cancer risk assessment tool (BCRAT) scores were considerably more likely to use tamoxifen. Women with BCRAT scores between 3% and 6% were nearly five times as likely to use tamoxifen (OR = 4.97; 95% CI, 3.57-6.24), and women who had more than one sister with breast cancer were more than six times likely to use tamoxifen (OR = 6.53; 95% CI, 4.66-9.12).
Women who had breast biopsy were twice as likely to use tamoxifen as those who did not have a biopsy (OR = 2.06; 95% CI, 1.65-2.56).
Researchers observed a high level of tamoxifen discontinuation among the cohort.
Nearly half (46%) of users had discontinued by 4.5 years, and the median duration for use among former users was 3 years.
Women who used raloxifene after tamoxifen were considerably less likely to complete 5 years of tamoxifen therapy (OR = 0.45; 95% CI, 0.27-0.75).
The findings may help guide patients and their clinicians when they consider whether to use tamoxifen, researchers wrote.
“[This study] highlights that the estimated benefit is not the same for all women,” Nichols said in the release. “Women need to go and have a very specific conversation with their providers about what their health looks like at the time and whether this is a reasonable option for them.” – by Anthony SanFilippo
Disclosure: The researchers report no relevant financial disclosures.