Through the looking glass at early-life exposures and breast cancer risk.

The global increase in the proportion of women diagnosed with breast cancer, inadequate access to screening and high cost of treatment for breast cancer argue strongly for a greater focus on preventive strategies. But at what age is it appropriate to begin targeting preventive approaches? The recognized role of perinatal nutrition in neurologic development and the relation of maternal nutritional status to birthweight and subsequent risk of hypertension, diabetes, and cardiovascular disease identify pregnancy and early childhood as potential phases for prevention. This review examines indicators of hormonal and nutritional exposures in early life and breast cancer risk through the lens of the life course paradigm integrated with maternal and child health research and methodology. Compared to women who were normal birthweight (2500-3999 g), women who weighed>or=4,000 g at birth have a 20 percent to 5-fold increased risk of premenopausal breast cancer. Women born preterm and likely to be small- or large-for-date also have an increased risk. Birth length is directly associated with risk and has a larger magnitude of effect than birthweight. Prior preeclamptics and their daughters have a lower risk of breast cancer than comparable normotensives. An association between infant feeding practices and breast cancer is unclear without improved exposure assessment and analysis. Rapid childhood and pubertal linear growth increases breast cancer risk, while greater body fat over the same periods reduces risk. Growth data thus far have not been calculated in Z-scores from reference growth curves for comparison across studies. Events and secular trends influencing birth cohorts may not be adequately addressed, thereby limiting the interpretation and implications of the findings. Research in nonhuman primates may help uncover underlying mechanisms.