Angiogenic Balance in Pregnancy and Subsequent Breast Cancer Risk and Survival: A Population Study

Background: Women with a history of preeclampsia have reduced breast cancer risk. Because preeclampsia is characterized by an imbalance in angiogenic factors, we assessed pregnancy levels of placental growth factor (PIGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and soluble endoglin (s-endoglin) and subsequent breast cancer risk. Methods: In a case-control study among 26,744 pregnant women, we compared angiogenic factors between 145 women who later developed invasive breast cancer and 400 controls. The angiogenic factors were determined with ELISA in blood samples collected in weeks (median) 10, 23, and 35 of the baseline pregnancy. Results: Concentrations of PIGF, sFlt-1, and s-endoglin did not differ between women who later developed breast cancer and control women, and odds ratios across quartiles of each factor did not indicate any association in blood samples from gestational week 10, 23, or 35. During pregnancy, there was a general increase in each angiogenic factor, but degree of increase from one sampling period to the next was not associated with later breast cancer risk. Among cases, 22 of 145 died from breast cancer during 10 years of follow-up, but there was no consistent indication that angiogenic factors measured in pregnancy up to several years before diagnosis were associated with case fatality. Conclusions: The results of this nested case-control study, based on blood samples collected up to three time points during pregnancy, and subsequent cancer follow-up, do not provide any evidence that pregnancy levels of PIGF, sFlt-1, and s-endoglin are associated with breast cancer risk later in life. (Cancer Epidemiol Biomarkers Prev 2009;18(7):2074-8)