High Basic Fibroblast Growth Factor Levels in Nipple Aspirate Fluid Are Correlated with Breast Cancer

Abstract

PURPOSEThe angiogenic basic fibroblast growth factor (bFGF) and vascular endothelial growth factor are important in malignant breast epithelial growth. Nipple aspirate fluid (NAF) is a physiologic fluid collected noninvasively that contains proteins secreted by the breast ductal epithelium and may contain markers of breast cancer. The purpose of this study was to determine whether high concentrations of bFGF and vascular endothelial growth factor in NAF would be associated with in situ and invasive breast cancer, and whether prostate-specific antigen, a marker in NAF associated with breast cancer, would improve our ability to determine which subjects had the disease. METHODSBoth bivariate and multivariate analyses were performed to determine the effects of race, menopausal status, bFGF concentration, and prostate-specific antigen on cancer risk. Bivariate analysis was also performed to determine the relationship between vascular endothelial growth factor concentration and cancer risk. RESULTSMean NAF bFGF levels were higher in women with breast cancer than in those without (19.2 vs 1.74 ng/g). Vascular endothelial growth factor was not associated with breast cancer. Race and menopausal status did not significantly affect the relationship between bFGF and cancer risk. bFGF, race, and menopausal status were each independent predictors of breast cancer, with bFGF being the most important. With knowledge of all three variables, the model was 89.9% sensitive and 69.0% specific in predicting which women had breast cancer. Adding prostate-specific antigen increased the sensitivity to 90.9% and the specificity to 83.3%. In subjects with NAF bFGF > 150 ng/g and prostate-specific antigen < 100 ng/g, 94.1% (32/34) of subjects had cancer. For women with NAF prostate-specific antigen > 100 ng/ g and bFGF < 150 ng/g, 90.5% were cancer free. CONCLUSIONSbFGF concentration in NAF is directly associated with breast cancer, regardless of race and menopausal status. NAF bFGF may prove helpful in the early detection of breast cancer.