Oestrogen plus progestin hormone therapy is an established risk factor for breast cancer in postmenopausal women. It was 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.

In this pooled cohort analysis, it has been 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.

The study has 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 hazard ratio 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 more than 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.

In conclsuion, 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. ( Xagena_2025 )

O’Brien KM et al, Lancet Oncol 2025;26(7):911-923

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