Placental ischemia and breast cancer risk after preeclampsia: tying the knot

Although hypertensive disorders of pregnancy, such as preeclampsia, continue to be a significant source of maternal and fetal morbidity and mortality, there is emerging evidence that effects of the preeclamptic syndrome persist into later life. In contrast to recent studies that have reported that formerly preeclamptic women are at increased risk for cardiovascular disease, it appears that preeclampsia may be associated with a decreased risk of breast cancer. Recent investigations have provided exciting new insights into potential mechanisms underlying the pathogenesis of preeclampsia and some of these findings may bear relevance to the anticancer effects reported in the epidemiological literature. Placental ischemia is regarded to be a primary factor in preeclampsia and the ischemic placenta produces a variety of factors that generate profound effects on endothelial cell function and the cardiovascular system during pregnancy. Moreover, several of these factors are reportedly elevated many years after preeclamptic pregnancies. This group of molecules includes factors such as soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin/CD105 (sEng) and various cytokines. Many of these factors have been strongly associated with cancer incidence and, hence, could contribute to the modification of cancer risk observed in these women. Therefore, identifying potential connections between placental dysfunction and future cancer risk is an important endeavor towards realizing novel therapeutic regimens for cancer patients.