Evidence of prenatal influences on breast cancer risk.

Intrauterine exposure to high concentrations of endogenous pregnancy oestrogens may be important in the aetiology of breast cancer. In a nested case-control study we have assessed the relation between breast cancer risk and indicators of pregnancy oestrogen concentrations; pre-eclampsia/eclampsia is negatively related and measures of fetal size are positively related to oestrogen concentrations. Standard records for women born at Uppsala University Hospital between 1874 and 1954 were linked with records of invasive breast cancer cases, identified through their unique national registration numbers in the Swedish Cancer Registry during 1958-90. For each breast cancer case, we selected as potential controls female offspring of the first three mothers admitted to the hospital after the case's mother; only controls still living in Sweden and free from breast cancer when it was diagnosed in the case were finally included. Conditional logistic regression analysis was done for 458 breast cancer cases and 1197 matched controls. Pre-eclampsia/eclampsia was associated with a breast cancer rate ratio of 0.24 (95% confidence interval 0.09-0.70, p = 0.01). Linear trends for breast cancer incidence with increasing birth weight, birth length, and placental weight were positive but not significant. Thus, prenatal factors are important in breast carcinogenesis. Concentrations of pregnancy oestrogens may be one such factor, but other prenatal or perinatal factors cannot be excluded.