Placental morphology and daughter's breast density in mid-life: Prospective evidence from the Child Health and Development Studies

Elongated shape and decreased thickness of the placenta occur in response to environmental stress such as high altitude and prenatal smoking. We previously observed an association between prenatal smoke exposure and decreased mammographic density, a known predictor of breast cancer. Here we test the hypothesis that placental morphology is associated with daughter's mammographic density at ages 39-49 years in a 50-year follow-up of a subset of the Child Health and Development Studies. We collected and analyzed mammographic density in 235 women who had placental characteristics measured at the time of their birth using the Benirschke protocol. We used Proc Mixed (Statistical Analysis Systems) to estimate prenatal predictors of mammographic density (dense area divided by breast area multiplied by 100). Shape and thickness of the placenta was associated with daughter's breast density. Thin, elongated placentas were associated with lower breast density while thick, elongated placentas were associated with higher density (p =0.02 for test of heterogeneity) before and after adjustment for maternal weight, gestation, placental weight, birthweight, and prenatal smoking. The highest quartile for elliptical area was significantly associated with a 16% decline in percent density when the placenta was also thin (95%CL=-3%,-28%, p=0.02), but when the placenta was thick the same change was associated with a non-significant 11% increase in breast density (95%CL=-5,29, p=0.16). Placental morphology may influence the structure of the breast and have implications for breast cancer risk in mid-life mediated by breast density. Environmental factors may influence placental morphology presenting opportunities for breast cancer prevention.