Perinatal factors increase breast cancer risk

Emerging evidence suggests that breast cancer may originate during early life. In particular, offspring of mothers who during pregnancy exhibited behaviors that are associated with increased incidence of breast cancer, may be at risk. These behaviors include intake of high fat diet or alcohol, or stressful life style. We have found that neonatal exposure to handling that leads to improved ability to cope with stress, reduces 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in rats. Further, our results indicate that maternal exposure to high fat diet increases the incidence of DMBA-induced mammary tumors in female offspring. High fat diet also increases serum 17β-estradiol (E2) levels in pregnant animals. These results support the hypothesis that in utero concentrations of estrogens play a critical role in the vulnerability to develop breast cancer. The mechanism of estrogen action might be related to its effect on the induction of epithelial hyperplasia and altered breast differentiation. These events then increase the rate of genetic/epigenetic changes that increase the possibility of neoplastic transformation. Increased pregnancy estrogens may also lead to behavioral alterations in the offspring. This could explain the proposed association between certain behavioral patterns and increased tumorigenity. Our results in transgenic mice overexpressing transforming growth factor α (TGFα) are in accordance with this interpretation. The male TGFα mice exhibit elevated serum E2 levels, impaired ability to cope with stress, increased voluntary alcohol intake and high incidence of spontaneous hepatocellular tumors. These findings indicate that animal models offer a unique opportunity to investigate the role of timing of risk behaviors on breast cancer. They are also useful in the attempts to understand the mechanism of early estrogen action on mammary tumorigenesis.