BJC Open article

British Journal of Cancer (2016) 115, 607–615. doi:10.1038/bjc.2016.231 www.bjcancer.com
Published online 28 July 2016

Menopausal hormone therapy and breast cancer: what is the true size of the increased risk?

Michael E Jones1, Minouk J Schoemaker1, Lauren Wright1, Emily McFadden1,6, James Griffin1,7, Dawn Thomas1, Jane Hemming1, Karen Wright2, Alan Ashworth3,4,5,8 and Anthony J Swerdlow1,3

  1. 1Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK
  2. 2The National Cancer Registration Service–Eastern Office, Public Health England, Cambridge CB21 5XA, UK
  3. 3Division of Breast Cancer Research, The Institute of Cancer Research, London SW7 3RP, UK
  4. 4Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research, London SW7 3RP, UK
  5. 5Division of Molecular Pathology, The Institute of Cancer Research, London SW7 3RP, UK

Correspondence: Dr ME Jones, E-mail: Michael.Jones@icr.ac.uk

6Current address: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, OX2 6GG, UK

7Current address: Warwick Clinical Trials Unit, Division of Health Sciences, Warwick Medical School, The University of Warwick, Coventry, CV4 7AL, UK

8Current address: UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94158, USA

Received 6 April 2016; Revised 30 June 2016; Accepted 6 July 2016
Advance online publication 28 July 2016





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, 58148 had reached menopause and 96% had completed a follow-up questionnaire. Among 39183 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.


bias (epidemiology); breast neoplasms; cohort studies; oestrogen replacement therapy