Quantifying mediating effects of endogenous estrogen and insulin in the relation between obesity, alcohol consumption and breast cancer

Cancer Epidemiology, Biomarkers & Prevention, 06/04/2012

Hvidtfeldt UA et al. – The relation of BMI with breast cancer was partly mediated through estradiol and, to a greater extent, through insulin. The findings provide support for evaluation of interventions to lower insulin and estrogen levels in overweight and obese postmenopausal women to reduce breast cancer risk


  • We combined data from two case-cohort studies based in the Women's Health Initiative Observational Study with serum estradiol levels, one of which also had insulin levels.
  • A total of 1601 women (601 cases) aged 50-79 years who were not using hormone therapy at enrollment were included.
  • Mediating effects were estimated by applying a new method based on the additive hazard model.


  • A 5-unit increase in BMI was associated with 50.0 (95% CI, 23.2; 76.6) extra cases per 100,000 women at risk per year.
  • Of these, 23.8% (95% CI, 2.9; 68.4) could be attributed to estradiol and 65.8% (95% CI, 13.6; 273.3) through insulin pathways.
  • The mediating effect of estradiol was greater (48.8%; 95% CI, 18.8; 161.1) for BMI when restricted to ER+ cases.
  • Consuming 7+ drinks/week compared to abstinence was associated with 164.9 (95% CI, 45.8; 284.9) breast cancer cases per 100,000, but no significant contribution from estradiol was found.
  • The effect of alcohol on breast cancer was restricted to ER+ breast cancers.

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