Unopposed estrogen therapy was linked to a lower risk of breast cancer before age 55, while estrogen plus progestin therapy was associated with higher risk in long-term users and women with intact reproductive organs, according to a recent study.
The analysis included data from 459,476 women across 10 prospective cohorts in North America, Europe, Asia, and Australia. Participants were aged 16 to 54 years at enrollment (mean age = 42 years) and were followed for a median of 7.8 years. A total of 8,455 women developed young-onset breast cancer during follow-up.
Among all participants, 15% reported using hormone therapy: 6% had used estrogen plus progestin therapy, and 5% had used unopposed estrogen therapy. Researchers used cohort-stratified, multivariable-adjusted Cox proportional hazards models to estimate the associations between hormone therapy and breast cancer incidence. They accounted for potential confounders including age, BMI, education, reproductive history, and surgical status.
Any hormone therapy use was not associated with a significant change in breast cancer risk (hazard ratio [HR] = 0.96). Unopposed estrogen therapy was associated with a modest reduction in risk (HR = 0.86), which corresponded to an absolute risk difference of –0.5%. The inverse association appeared stronger among long-term users (HR = 0.80) and women who initiated therapy before age 45 (HR = 0.77), although confidence intervals for several subgroup estimates were close to 1. These findings are based on observational data and should not be interpreted as evidence of causality.
In contrast, estrogen plus progestin therapy showed a positive association with young-onset breast cancer (HR = 1.1). The risk was higher among current users (HR = 1.21), long-term users (HR = 1.18), and women without a history of hysterectomy or bilateral oophorectomy (HR = 1.15). Subtype analyses showed that estrogen plus progestin therapy was more strongly associated with estrogen receptor–negative breast cancer (HR = 1.44) and triple-negative breast cancer (HR = 1.5).
These findings were consistent in time-updated models from four cohorts that provided longitudinal hormone therapy data. The researchers concluded that unopposed estrogen therapy may be associated with reduced risk of young-onset breast cancer, whereas estrogen plus progestin therapy may increase risk, particularly among women with an intact uterus and ovaries.
The researchers reported no competing interests.
Source: The Lancet Oncology