Objectives: In response to a hypothesis by Trichopoulos that risk of adult breast cancer is related to high estrogen exposure in utero, studies have been undertaken using proxy indicators of prenatal estrogens. The epidemiologic studies addressing these early factors will be reviewed, consistency with proposed biologic mechanisms will be addressed and recommendations for future research will be presented.
Methods: All studies identified in the literature addressing these in utero and early life factors related to adult breast cancer will be included in the review. The study results will be summarized by risk factor, followed by commentary on the findings.
Results: Review of epidemiologic studies suggests strong risks related to having been born of a twin pregnancy and reduced risks from a preeclamptic or eclamptic pregnancy. Birthweights greater than 4,000 grams have been associated with relative risks of 1.5-1.7 for breast cancer compared with normal birthweights (2,500-2,999 grams). Having been breastfed as an infant has been associated with a 20-35% reduction in risk of premenopausal breast cancer in four of six studies evaluating this factor. Some studies suggest an influence of older maternal age, perhaps only for firstborn offspring, but the data are not consistent. Smoking during the pregnancy does not seem to impart any risk for the daughter, severe nausea for two or three trimesters may be related to increased risk, and results are inconsistent for birth length, placental weight and gestational age.
Conclusion: Although the results from epidemiologic studies assessing prenatal exposures are consistent with the hypothesis concerning estrogen exposure, the specific biologic mechanisms remain largely unknown. Relatively few epidemiologic studies have been published addressing these novel hypotheses; more studies with innovative research methods and analytic approaches are warranted to evaluate these exposures in the distant past.