title: Menopausal hormone therapy and breast cancer: what is the true size of the increased risk?
abstract: Menopausal hormone therapy (MHT) increases breast cancer risk; however, most cohort studies omit MHT use after enrolment and many infer menopausal age.
  
  
  
  We used information from serial questionnaires from the UK Generations Study cohort to estimate hazard ratios (HRs) for breast cancer among post-menopausal women with known menopausal age, and examined biases induced when not updating data on MHT use and including women with inferred menopausal age.
  
  
  
  Among women recruited in 2003-2009, at 6 years of follow-up, 58 148 had reached menopause and 96% had completed a follow-up questionnaire. Among 39 183 women with known menopausal age, 775 developed breast cancer, and the HR in relation to current oestrogen plus progestogen MHT use (based on 52 current oestrogen plus progestogen MHT users in breast cancer cases) relative to those with no previous MHT use was 2.74 (95% confidence interval (CI): 2.05-3.65) for a median duration of 5.4 years of current use, reaching 3.27 (95% CI: 1.53-6.99) at 15+ years of use. The excess HR was underestimated by 53% if oestrogen plus progestogen MHT use was not updated after recruitment, 13% if women with uncertain menopausal age were included, and 59% if both applied. The HR for oestrogen-only MHT was not increased (HR=1.00; 95% CI: 0.66-1.54).
  
  
  
  Lack of updating MHT status through follow-up and inclusion of women with inferred menopausal age is likely to result in substantial underestimation of the excess relative risks for oestrogen plus progestogen MHT use in studies with long follow-up, limited updating of exposures, and changing or short durations of use.
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Jones
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.
authors.forename: Minouk J
authors.initials: MJ
authors.lastname: Schoemaker
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.
authors.forename: Lauren
authors.initials: L
authors.lastname: Wright
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.
authors.forename: Emily
authors.initials: E
authors.lastname: McFadden
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.
authors.forename: James
authors.initials: J
authors.lastname: Griffin
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.
authors.forename: Dawn
authors.initials: D
authors.lastname: Thomas
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Hemming
authors.affiliation: The National Cancer Registration Service-Eastern Office, Public Health England, Cambridge CB21 5XA, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Wright
authors.affiliation: Division of Breast Cancer Research, The Institute of Cancer Research, London SW7 3RP, UK.|Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research, London SW7 3RP, UK.|Division of Molecular Pathology, The Institute of Cancer Research, London SW7 3RP, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Ashworth
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.|Division of Breast Cancer Research, The Institute of Cancer Research, London SW7 3RP, UK.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Swerdlow
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology*; D015331:Cohort Studies; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008875:Middle Aged