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Risks of ovarian, breast, and corpus uteri cancer in women treated with assisted reproductive technology in Great Britain, 1991-2010: data linkage study including 2.2 million person years of observation

BMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k2644 (Published 11 July 2018) Cite this as: BMJ 2018;362:k2644
  1. Carrie L Williams, NIHR research fellow1,
  2. Michael E Jones, statistician2,
  3. Anthony J Swerdlow, professor2,
  4. Beverley J Botting, reader1,
  5. Melanie C Davies, consultant in reproductive medicine3,
  6. Ian Jacobs, professor3 4,
  7. Kathryn J Bunch, epidemiologist5,
  8. Michael F G Murphy, consultant epidemiologist6,
  9. Alastair G Sutcliffe, professor1
  1. 1UCL Great Ormond Street Institute of Child Health, London, UK
  2. 2Institute of Cancer Research, London, UK
  3. 3Institute for Women’s Health, University College London Hospitals, London, UK
  4. 4University of New South Wales, Sydney, NSW, Australia
  5. 5National Perinatal Epidemiology Unit, University of Oxford, Oxford, UK
  6. 6Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK
  1. Correspondence to: Prof A G Sutcliffe, Policy, Practice and Population Unit, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK a.sutcliffe{at}ucl.ac.uk (or @AlastairSutclif on Twitter)
  • Accepted 4 June 2018

Abstract

Objective To investigate the risks of ovarian, breast, and corpus uteri cancer in women who have had assisted reproduction.

Design Large, population based, data linkage cohort study.

Setting and participants All women who had assisted reproduction in Great Britain, 1991-2010, as recorded by the Human Fertilisation and Embryology Authority (HFEA).

Interventions HFEA fertility records for cohort members were linked to national cancer registrations.

Main outcome measures Observed first diagnosis of ovarian, breast, and corpus uteri cancer in cohort members were compared with age, sex, and period specific expectation. Standardised incidence ratios (SIRs) were calculated by use of age, sex, and period specific national incidence rates.

Results 255 786 women contributed 2 257 789 person years’ follow-up. No significant increased risk of corpus uteri cancer (164 cancers observed v 146.9 cancers expected; SIR 1.12, 95% confidence interval 0.95 to 1.30) was found during an average of 8.8 years’ follow-up. This study found no significantly increased risks of breast cancer overall (2578 v 2641.2; SIR 0.98, 0.94 to 1.01) or invasive breast cancer (2272 v 2371.4; SIR 0.96, 0.92 to 1.00). An increased risk of in situ breast cancer (291 v 253.5; SIR 1.15, 1.02 to 1.29; absolute excess risk (AER) 1.7 cases per 100 000 person years, 95% confidence interval 0.2 to 3.2) was detected, associated with an increasing number of treatment cycles (P=0.03). There was an increased risk of ovarian cancer (405 v 291.82; SIR 1.39, 1.26 to 1.53; AER 5.0 cases per 100 000 person years, 3.3 to 6.9), both invasive (264 v 188.1; SIR 1.40, 1.24 to 1.58; AER 3.4 cases per 100 000 person years, 2.0 to 4.9) and borderline (141 v 103.7; SIR 1.36, 1.15 to 1.60; AER 1.7 cases per 100 000 person years, 0.7 to 2.8). Increased risks of ovarian tumours were limited to women with endometriosis, low parity, or both. This study found no increased risk of any ovarian tumour in women treated because of only male factor or unexplained infertility.

Conclusions No increased risk of corpus uteri or invasive breast cancer was detected in women who had had assisted reproduction, but increased risks of in situ breast cancer and invasive and borderline ovarian tumours were found in this study. Our results suggest that ovarian tumour risks could be due to patient characteristics, rather than assisted reproduction itself, although both surveillance bias and the effect of treatment are also possibilities. Ongoing monitoring of this population is essential.

Footnotes

  • Contributors: CLW jointly conceptualised and designed the study, devised the linkage protocol, supervised the linkage, carried out the analysis, interpreted data, drafted the initial manuscript, and approved the final manuscript as submitted. MEJ jointly conceptualised and designed the study, jointly supervised the analysis, interpreted data, reviewed and revised the manuscript, and approved the final manuscript as submitted. AJS jointly conceptualised and designed the study, interpreted data, reviewed and revised the manuscript, and approved the final manuscript as submitted. BJB jointly conceptualised and designed the study, jointly supervised the analysis, interpreted data, reviewed and revised the manuscript, and approved the final manuscript as submitted. MCD jointly conceptualised and designed the study, interpreted data, reviewed and revised the manuscript, and approved the final manuscript as submitted. IJ jointly conceptualised and designed the study, interpreted data, reviewed and revised the manuscript, and approved the final manuscript as submitted. KJB jointly conceptualised and designed the study, interpreted data, reviewed and revised the manuscript, and approved the final manuscript as submitted. MFGM jointly conceptualised and designed the study, interpreted data, reviewed and revised the manuscript, and approved the final manuscript as submitted. AGS jointly conceptualised and designed the study, interpreted data, reviewed and revised the manuscript, and had the final decision over submission of the approved the final manuscript. All authors had access to the data and take responsibility for the integrity of the data and accuracy of the data analysis. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. AGS acts as guarantor for this study.

  • Funding: This research was funded by Cancer Research UK (11704) and the National Institute for Health Research (NIHR; 405526 to CLW), and supported by the NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. This paper presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. IJ is funded by Breast Cancer Now. The Institute of Cancer Research acknowledges NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. AGS’s research on this project is partly funded by Medical Research Council grant number MR/L020335/1. No funders or sponsors had any role in the study design, data collection, analysis, interpretation of data and decision to submit for publication. All researchers are independent from funders and sponsors.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support for this study from Cancer Research UK and NIHR; MEJ additionally received funding from Breast Cancer Now, and KJB and MFGM received funding from the UK Department of Health and Children with Cancer UK during the study; IJ reports personal fees from Abcodia and Women’s Health Specialists, and receives royalties as co-inventor of the ROCA algorithm; MCD reports personal fees from the Centre for Reproductive and Genetic Health; the authors declare no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Approval of the study and waiver of the requirement for individual consent were obtained from the UK Health Research Authority Confidentiality Advisory Group and London Research Ethics Committee (references 5.04(b)/10 and 10/H0720/18, respectively).

  • Data sharing: No additional data are available, in compliance with ethical and governance regulations under which this research was undertaken.

  • AGS affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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