Intrauterine environments and breast cancer risk: meta-analysis and systematic review

We reviewed breast cancer studies published from January 1966 to February 2007 that included data on birth weight, birth order, maternal age, gestational age, twin status, and maternal or paternal smoking. Meta-analyses using random effect models were employed to summarize the results.We found that heavier birth weights were associated with increased breast cancer risk, with studies involving five categories of birth weight identifying odds ratios (ORs) of 1.24 (95% confidence interval [CI] 1.04 to 1.48) for 4,000 g or more and 1.15 (95% CI 1.04 to 1.26) for 3,500 g to 3,999 g, relative to a birth weight of 2,500 to 2,599 g. These studies provided no support for a J-shaped relationship of birthweight to risk. Support for an association with birthweight was also derived from studies based on three birth weight categories (OR 1.15 [95% CI 1.01 to 1.31] for ≥4,000 g relative to <3,000 g) and two birth weight categories (OR 1.09 [95% CI 1.02 to 1.18] for ≥3,000 g relative to <3,000 g). Women born to older mothers and twins were also at some increased risk, but the results were heterogeneous across studies and publication years. Birth order, prematurity, and maternal smoking were unrelated to breast cancer risk.Our findings provide some support for the hypothesis that in utero exposures reflective of higher endogenous hormone levels could affect risk for development of breast cancer in adulthood.Intrauterine environmental exposures to endogenous or exogenous hormones, notably estrogens, may influence the subsequent development of breast cancer in offspring [1]. During pregnancy, levels of circulating estrogens and other hormones with growth-enhancing properties are at least 10 times higher than those in nonpregnant women, with increases seen with advancing gestational age [2-4]. The hypothesis that breast cancer in daughters may be influenced by the intrauterine environment is receiving increased attention [5]. Perinatal factors, including birth weight, birth order, mate