Hormone therapy's impact on young-onset breast cancer risk varies by type

New research shows that using oestrogen hormone therapy alone may reduce the risk of young-onset breast cancer, while combining it with progestin could result in a risk increase among women with intact uterus and ovaries.

Researchers conducted a pooled cohort analysis using data from 10–13 prospective cohorts from North America, Europe, Asia, and Australia. In these cohorts, the women were followed for incident breast cancer until age 55 years.

A total of 459,476 women between 16 and 54 years of age (mean 42.0 years) were included in the analysis. Young-onset breast cancer occurred in 8,455 (2 percent) women over a median follow-up of 7.8 years). Hormone therapy use was reported by 15 percent of women, including 6 percent who used oestrogen plus progestin and 5 percent who used unopposed oestrogen.

Hormone therapy of any type showed no association with incident young-onset breast cancer (hazard ratio [HR], 0.96, 95 percent confidence interval [CI], 0.88–1.04), but ever oestrogen hormone therapy use showed a protective association (HR, 0.86, 95 percent CI, 0.75–0.98; risk difference, –0.5 percent, 95 percent CI, –1.0 to –0.0).

On the other hand, ever oestrogen plus progestin hormone therapy use was associated with a 10-percent increase in the risk of young-onset breast cancer (HR, 1.10, 95 percent CI, 0.98–1.24). The risk further increased with long-term use (>2 years: HR, 1.18, 95 percent CI, 1.01–1.38) and among women without hysterectomy or bilateral oophorectomy (HR, 1.15, 95 percent CI, 1.02–1.31).

The null association observed between oestrogen hormone therapy and young-onset breast cancer risk was consistent across all breast cancer subtypes. Meanwhile, oestrogen plus progestin hormone therapy was more strongly associated with oestrogen receptor-negative disease (HR, 1.44, 95 percent CI, 1.11–1.88) and triple-negative disease (HR, 1.50, 95 percent CI, 1.02–2.20).

These findings mostly align with results from studies of hormone use and later-onset breast cancer and may inform clinical recommendations among younger women, according to the researchers.