Update of the impact of menopausal hormone therapy on breast cancer risk

Eur J Cancer. 2025 May 2:220:115340. doi: 10.1016/j.ejca.2025.115340. Epub 2025 Mar 11.

Abstract

Background: We assessed menopausal hormone therapy (MHT) -related invasive breast cancer (BC) risks among more recent MHT users to compare this data with older national and international data.

Methods: We identified in this nationwide cohort study MHT users (n = 357 928) in 1994-2019 from the medical reimbursement register and age-matched non-users (n = 351 735) from the national population register and followed them for the occurrence of invasive BC with the aid of the Finnish Cancer Registry. The unadjusted BC risks were calculated as odds ratios (ORs) and 95 % confidence intervals (CIs).

Results: During a median of 18 years and 13 million person-years, 23 571 MHT users (6.6 %) and 17 192 non-users (4.9 %) were diagnosed with invasive BC (p < 0.001), and the median detection year was 2011. Ever use of estrogen-only therapy for 5-9 years (OR 1.61; 95 % CI 1.51-1.71) or tibolone for ≤ 10 years (1.30; 1.02-1.67) was accompanied by smaller risk elevations than use of estrogen-progestogen therapy (EPT) for the same duration (1.82; 1.76-1.88 and 1.98; 1.91-2.06). Dydrogesterone-EPT for 5-9 years was associated with a smaller risk increase (1.32; 1.12-1.55) than other EPT regimens (1.76-2.16; 1.62-2.30). The BC risks remained elevated 5-10 years after cessation of MHT with most of the regimens.

Conclusions: Despite possible changes towards safer MHT prescribing, our data collected largely in early millennium show at least as large BC risk elevations in MHT users as seen in older studies.

Keywords: Breast neoplasms; Dydrogesterone; Estradiol; Estrogen replacement therapy; Hormone replacement therapy; Progestins.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms* / chemically induced
  • Breast Neoplasms* / epidemiology
  • Breast Neoplasms* / pathology
  • Cohort Studies
  • Estrogen Replacement Therapy* / adverse effects
  • Female
  • Finland / epidemiology
  • Hormone Replacement Therapy* / adverse effects
  • Humans
  • Menopause*
  • Middle Aged
  • Progestins / adverse effects
  • Registries
  • Risk Assessment
  • Risk Factors

Substances

  • Progestins