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Prospective Data: Breast Cancer Risk and Menopausal Hormone Therapy


  • The Collaborative Group on Hormonal Factors in Breast Cancer (Lancet, 2019) reviewed epidemiologic propective data from multiple sources, both published and unpublished, to determine the relationship between menopausal hormone therapy (MHT) and breast cancer risk


  • From 1992, the Collaboration searched and reviewed potentially eligible epidemiologic studies
    • Eligible epidemiological studies have been sought regularly by computer-aided literature searches, manual searches of review articles, written communications, and discussions at scientific meetings
  • Design
    • Prospective studies | Nested case-control design
    • 4 randomly selected controls per case of invasive breast cancer
    • Matched for age, year of birth, and region
  • Included data
    • Individual participant data
    • Prospective studies with information on the type and timing of MHT use
  • Current MHT users included up to 5 years (mean 1.4 years) after last-reported MHT use
  • All analyses included only postmenopausal women
    • Known age at natural menopause (or at bilateral oophorectomy) or
    • Unknown age at menopause but age ≥55 years
  • Logistic regression used to calculate adjusted risk ratios (RRs)
    • Compared particular MHT groups of MHT users vs never users


  • 58 studies
    • Cases: 143,887 postmenopausal women with invasive breast cancer
    • Controls: 424,972 without breast cancer
    • Mean age: 50 years at menopause | 50 years at starting MHT
  • All MHT types, except vaginal estrogen, were associated with increased risk for breast cancer
  • Excess risk for breast cancer was evident even during 1 to 4 years
    • Estrogen-progestogen: RR 1.60 (95% CI, 1.52 to 1.69)
    • Estrogen-only: RR 1.17 (95% CI, 1.10 to 1.26)
  • Risk doubled during years 5–14
    • Estrogen-progestogen: RR 2.08 (95% CI, 2.02 to 2.15)
    • Estrogen-only: RR 1.33 (95% CI, 1.28 to 1.37)
  • Regardless of preparation type, risks during years 5–14 of current use were
    • Greater with daily vs less frequent progestogen use
    • Greater for ER-positive tumors than for ER-negative tumors
    • Similar regardless if MHT was started at ages 40–44, 45–49, 50–54, and 55–59 years
    • Reduced if MHT started >60 years  
  • Some excess risk persisted for more than 10 years after cessation of MHT, dependent on duration of use
    • Little excess risk with <1 year of MHT use
  • BMI increased breast cancer risk (ER-positive) for never users but not current users


  • Every MHT type, except vaginal estrogens, was associated with excess breast cancer risks
    • Risk related to duration of use | Greater for estrogen-progestogen vs estrogen-only preparations
  • In developed countries starting at 50 years of age, breast cancer incidence at ages 50–69 years would increase by approximately
    • 1/50 users of estrogen plus daily progestogen preparations
    • 1/ 70 users of estrogen plus intermittent progestogen preparations
    • 1/ 200 users of estrogen-only preparations

Joint Royal College of Obstetricians and Gynaecologists & British Menopause Society statement in response to the Lancet study on HRT use and breast cancer risk

  • Study confirms known, small increased risk of breast cancer
  • The statement makes the following key points

For most women, HRT helps to manage menopausal symptoms and is safe

To put the risk into context, a woman has greater risk of developing breast cancer if she is overweight or obese compared to taking HRT

Women must be aware of the effect of obesity and alcohol which increase the risk of breast cancer and modifies the additional risk of HRT 

Learn More – Primary Sources:

Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence

RCOG/BMS response to Lancet study on HRT use and breast cancer risk

Hormone replacement therapy (HRT): further information on the known increased risk of breast cancer with HRT and its persistence after stopping