Breast cancer risk in relation to history of preeclampsia and hyperemesis gravidarum: Prospective analysis in the Generations Study

Lauren B Wright, Minouk J Schoemaker, Michael E Jones, Alan Ashworth, Anthony J Swerdlow

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Preeclampsia and hyperemesis gravidarum are pregnancy complications associated with altered sex hormone levels. Previous studies suggest preeclampsia may be associated with a decreased risk of subsequent breast cancer and hyperemesis with an increased risk, but the evidence remains unclear. We used data from the Generations Study, a large prospective study of women in the United Kingdom, to estimate relative risks of breast cancer in relation to a history of preeclampsia and hyperemesis using Cox regression adjusting for known breast cancer risk factors. During 7.5 years average follow-up of 82,053 parous women, 1,969 were diagnosed with invasive or in situ breast cancer. Women who had experienced preeclampsia during pregnancy had a significantly decreased risk of premenopausal breast cancer (hazard ratio (HR) =0.67, 95% confidence interval (CI): 0.49-0.90) and of HER2-enriched tumours (HR = 0.33, 95% CI: 0.12-0.91), but there was no association with overall (HR = 0.90, 95% CI: 0.80-1.02) or postmenopausal (HR = 0.97, 95% CI: 0.85-1.12) breast cancer risk. Risk reductions among premenopausal women were strongest within 20 years since the last pregnancy with preeclampsia. Hyperemesis was associated with a significantly increased risk of HER2-enriched tumours (HR = 1.76, 95% CI: 1.07-2.87), but not with other intrinsic subtypes or breast cancer risk overall. These results provide evidence that preeclampsia is associated with a decreased risk of premenopausal and HER2-enriched breast cancer and that hyperemesis, although not associated with breast cancer risk overall, may be associated with raised risk of HER2-enriched tumours.

Original languageEnglish
Pages (from-to)782-792
Number of pages11
JournalInternational Journal of Cancer
Issue number4
Publication statusPublished - 15 Aug 2018

Bibliographical note

© 2018 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.


  • Adult
  • Breast Carcinoma In Situ/epidemiology
  • Breast Neoplasms/complications
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperemesis Gravidarum/complications
  • Middle Aged
  • Neoplasm Invasiveness
  • Postmenopause
  • Pre-Eclampsia/epidemiology
  • Pregnancy
  • Premenopause
  • Proportional Hazards Models
  • Prospective Studies
  • Receptor, ErbB-2/metabolism
  • Risk Factors
  • United Kingdom/epidemiology

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