Background: Although ecologic association and animal studies support a direct effect of dietary fat on the development of breast cancer, results of epidemiologic studies have been inconclusive.
Methods: We prospectively analyzed the association between fat consumption and the incidence of postmenopausal invasive breast cancer in the National Institutes of Health-AARP Diet and Health Study, a US cohort comprising 188,736 postmenopausal women who completed a 124-item food-frequency questionnaire in 1995-1996. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models with adjustment for energy and potential confounding factors. All statistical tests were two-sided.
Results: Over an average follow-up of 4.4 years, the cohort yielded 3501 cases of invasive breast cancer. The hazard ratio of breast cancer for the highest (median intake, 40.1% energy from total fat; 434 cases per 100,000 person-years) versus the lowest (median intake, 20.3% energy from total fat; 392 cases per 100,000 person-years) quintile of total fat intake was 1.11 (95% CI = 1.00 to 1.24; P(trend) = .017). The corresponding hazard ratio for a twofold increase in percent energy from total fat on the continuous scale was 1.15 (95% CI = 1.05 to 1.26). Positive associations were also found for subtypes of fat (hazard ratio for a twofold increase in percent energy from saturated fat = 1.13; 95% CI = 1.05 to 1.22; from monounsaturated fat, HR = 1.12; 95% CI = 1.03 to 1.21; from polyunsaturated fat, HR = 1.10, 95% CI = 1.01 to 1.20). Correction for measurement error in nutrient intakes, on the basis of a calibration substudy that used two 24-hour dietary recalls, strengthened the associations, yielding an estimated hazard ratio for total fat of 1.32 (95% CI = 1.11 to 1.58). Secondary analyses showed that associations between total, saturated, and monounsaturated fat intakes were confined to women who were not using menopausal hormone therapy at baseline.
Conclusion: In this large prospective cohort with a wide range of fat intake, dietary fat intake was directly associated with the risk of postmenopausal invasive breast cancer.