Breast cancer risk after caloric restriction during the 1944-1945 Dutch famine

Background: Data from animal models suggest that caloric restriction may reduce the risk of breast cancer, although not all dietary regimens produce similar effects. We examined whether caloric restriction imposed as a consequence of the 1944-1945 Dutch famine reduced the risk of breast cancer in women participating in a Dutch breast cancer screening program. Methods: Between 1983 and 1986, approximately 15 000 women, aged 2 to 33 years during the 1944-1945 Dutch famine, responded to a questionnaire about their famine experience. A famine exposure score, graded as absent, moderate, or severe exposure, was derived from answers regarding hunger, cold, and weight loss. During follow-up until January 2000, 585 women with incident breast cancer were identified by the regional cancer registry. The relationship between famine exposure and breast cancer risk was assessed by weighted Cox regression models, in which person-years lived for the entire cohort was extrapolated from data from a random sample of 15% of the cohort. Results: Women who were severely exposed to the famine had a statistically significantly higher risk of breast cancer (hazard ratio [HR] = 1.48, 95% confidence interval [CI] = 1.09 to 2.01) than women who were not exposed. Women who were moderately exposed to the famine had a 13% increased risk of breast cancer (HR = 1.13, 95% CI = 0.92 to 1.38; P-trend = 0.016). The association between famine exposure and breast cancer risk was stronger for women who were exposed between the ages of 2 and 9 years (severely exposed versus unexposed: HR = 2.01, 95% CI = 0.92 to 4.41) than for women who were exposed at older ages. Conclusions: The risk of breast cancer was increased in women who were severely exposed to a short but severe famine decades earlier. This result is compatible with data from the few animal studies investigating effects of short-term, transient caloric restriction.