Body size in early life and risk of breast cancer

Background: Body size in early life is inversely associated with adult breast cancer (BC) risk, but it is unclear whether the associations differ by tumor characteristics. Methods: In a pooled analysis of two Swedish population-based studies consisting of 6731 invasive BC cases and 28,705 age-matched cancer-free controls, we examined the associations between body size in early life and BC risk. Self-reported body sizes at ages 7 and 18 years were collected by a validated nine-level pictogram (aggregated into three categories: small, medium and large). Odds ratios (OR) and corresponding 95% confidence intervals (CI) were estimated from multivariable logistic regression models in case-control analyses, adjusting for study, age at diagnosis, age at menarche, number of children, hormone replacement therapy, and family history of BC. Body size change between ages 7 and 18 were also examined in relation to BC risk. Case-only analyses were performed to test whether the associations differed by tumor characteristics. Results: Medium or large body size at age 7 and 18 was associated with a statistically significant decreased BC risk compared to small body size (pooled OR (95% CI): comparing large to small, 0.78 (0.70-0.86), P-trend <0.001 and 0.72 (0. 64-0.80), P-trend <0.001, respectively). The majority of the women (similar to 85%) did not change body size categories between age 7 and 18. Women who remained medium or large between ages 7 and 18 had significantly decreased BC risk compared to those who remained small. A reduction in body size between ages 7 and 18 was also found to be inversely associated with BC risk (0.90 (0.81-1.00)). No significant association was found between body size at age 7 and tumor characteristics. Body size at age 18 was found to be inversely associated with tumor size (P-trend = 0.006), but not estrogen receptor status and lymph node involvement. For all analyses, the overall inferences did not change appreciably after further adjustment for adult body mass index. Conclusions: Our data provide further support for a strong and independent inverse relationship between early life body size and BC risk. The association between body size at age 18 and tumor size could be mediated by mammographic density.