Hormone therapy use and young-onset breast cancer: a pooled analysis of prospective cohorts included in the Premenopausal Breast Cancer Collaborative Group

Abstract

Background: Oestrogen plus progestin hormone therapy is an established risk factor for breast cancer in postmenopausal women. We examined the less well-studied association between exogenous hormones and breast cancer in young women, who might use hormone therapy after gynaecological surgery or to relieve perimenopausal symptoms.

Methods: In this pooled cohort analysis, we investigated the relationship between exogenous hormones and breast cancer in young women using data from 10-13 prospective cohorts from North America, Europe, Asia, and Australia. The participating cohorts followed up women for incident breast cancer until age 55 years. We used cohort-stratified, multivariable-adjusted Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% CI for associations of hormone therapy with incident young-onset breast cancer. We also estimated risk differences based on cumulative risk until age 55 years.

Findings: We included 459 476 women aged 16-54 years (mean 42·0 years [IQR 35·5-49·2]), of whom 8455 (2%) developed young-onset breast cancer (diagnosed before age 55 years; median follow-up 7·8 years [5·2-11·2]). Overall, 15% of participants reported using hormone therapy, with oestrogen plus progestin hormone therapy (6%) and unopposed oestrogen (5%) being the most common types. Cumulative risk of young-onset breast cancer was 4·1% in non-users. Hormone therapy of any type was not associated with incident young-onset breast cancer (HR 0·96 [95% CI 0·88 to 1·04]), but ever oestrogen hormone therapy use was inversely associated (0·86 [0·75 to 0·98]; risk difference -0·5% [-1·0 to -0·0]). The HR for ever oestrogen plus progestin hormone therapy and young-onset breast cancer was 1·10 (0·98 to 1·24), with positive associations observed for long-term use (1·18 [1·01 to 1·38] for >2 years) and use among women without hysterectomy or bilateral oophorectomy (1·15 [1·02 to 1·31]). Oestrogen hormone therapy and young-onset breast cancer association was similar for all breast cancer subtypes, but oestrogen plus progestin hormone therapy was more strongly associated with oestrogen receptor negative (1·44 [1·11 to 1·88]) and triple-negative disease (1·50 [1·02 to 2·20]) than with other subtypes.

Interpretation: Oestrogen hormone therapy use was inversely associated with young-onset breast cancer, and oestrogen plus progestin hormone therapy was associated with higher young-onset breast cancer incidence among women with intact uterus and ovaries. These findings largely parallel results from studies of hormone use and later-onset breast cancer and provide novel evidence for establishing clinical recommendations among younger women.

Funding: NIH Intramural Research Program.