Risk Factors for Specific Histopathological Types of Postmenopausal Breast Cancer in the NIH-AARP Diet and Health Study

Risk factor associations for rare breast cancer variants are often imprecise, obscuring differences between tumor types. To clarify differences, we examined risk factors for 5 histological types of breast cancer in the National Institutes of Health-AARP Diet and Health Study. Risk factor information was self-reported. We followed 192,076 postmenopausal women aged 5071 years from 19951996 through 2006. During that time period, 5,334 ductal, 836 lobular, 639 mixed ductal-lobular, 216 mucinous, and 132 tubular breast cancers were diagnosed. Hazard ratios and 95 confidence intervals were estimated using Cox proportional hazards regression. Heterogeneity was evaluated using case-only logistic regression. The strongest differences were for menopausal hormone therapy (P-heterogeneity 0.01) and age at first birth (P-heterogeneity 0.01). Risk of tubular cancer in relation to current menopausal hormone therapy (for current use vs. never use, hazard ratio (HR) 4.39, 95 confidence interval (CI): 2.77, 6.96) was several times stronger than risk of other histological types (range of HRs, 1.391.75). Older age at first birth was unassociated with risk of mucinous (for 30 years vs. 2024 years, HR 0.62, 95 CI: 0.27, 1.42) or tubular (HR 1.08, 95 CI: 0.51, 2.29) tumors, in contrast to clear positive associations with lobular (HR 1.82, 95 CI: 1.39, 2.37) and mixed ductal-lobular (HR 1.87, 95 CI: 1.39, 2.51) tumors. Differing associations for hormonal factors and mucinous and tubular cancers suggest etiologies distinct from those of common breast cancers.