Abstract

Abstract Background: Data comparing risk factors for in situ and invasive breast cancer, particularly with additional differentiation by ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS), are limited. Some previous studies have found similar risk relations for DCIS and invasive carcinoma, consistent with molecular and clinical data showing that DCIS lesions are non-obligate precursors of invasive breast cancer. However, some risk factors may act as promoters at later stages of carcinogenesis and may show differential associations with invasive as compared with in situ disease. We therefore evaluated the relationship between established breast cancer risk factors and the risk of DCIS, LCIS, and ductal and lobular invasive breast carcinomas. Methods: Among 192,315 postmenopausal women ages 50–71 years, enrolled in the NIH-AARP Diet and Health Cohort study, who did not have a prior history of any cancer, we identified 1,228 in situ (1,085 DCIS, 143 LCIS) and 6,185 invasive (5,345 ductal, 840 lobular) incident breast carcinomas from enrollment (1995–96) through last follow-up (2006). Participants provided information on established breast cancer risk factors via mailed questionnaires including: ages at menarche and first birth, breast cancer family history, alcohol use, and body mass index (BMI) or kg/m2. Relative risks (RR) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards regression. Results: Risk associations for age at menarche, age at first live birth, and family history of breast cancer were similar for DCIS, LCIS, and their invasive counterparts. Later age at menarche and earlier age at first live birth were associated with significant risk reductions while family history of breast cancer increased risk. Alcohol intake (>35 grams/day vs. none) was significantly associated with an increased risk of invasive breast cancer (RRductal=1.31, 95% CI: 1.13, 1.51; RRlobular=1.50, 95% CI: 1.04, 2.15) and suggestive of an increased risk of LCIS (RRLCIS=1.32, 95% CI: 0.51, 3.43); in contrast, no association was observed with DCIS (RRDCIS=1.04, 95% CI: 0.73, 1.50). BMI of 35 kg/m2 or greater was related to increased risk of invasive ductal carcinoma (RR=1.45, 95% CI: 1.31, 1.60) but not for in situ or invasive lobular cancers. These differences, however, did not translate into any statistically significant differences in risk factor associations for DCIS vs. LCIS, DCIS vs. ductal invasive, or LCIS vs. lobular invasive (p-heterogeneity >.10 for all comparisons). Conclusions: In this analysis, most established breast cancer risk factors showed similar associations for in situ and invasive ductal and lobular cancers among postmenopausal women, apart from marked obesity, which only increased risk for invasive ductal carcinoma. These data support the view that many of the risk factors considered in predicting risk of invasive breast cancer are also applicable to estimating risk of in situ breast cancer. Furthermore, obesity was differentially associated with increased risk of ductal invasive breast cancer, suggesting that this exposure may act as a promoter later in carcinogenesis. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A71.

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