High basic fibroblast growth factor levels in nipple aspirate fluid are correlated with breast cancer.
OBJECTIVE
The 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.


METHODS
Both 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.


RESULTS
Mean 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.


CONCLUSIONS
bFGF 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.
Department of Surgery, Thomas Jefferson University Philadelphia, Pennsylvania 19107, USA.
Robbin
R
Hsiung
Weizhu
W
Zhu
Gary
G
Klein
Wenyi
W
Qin
Anne
A
Rosenberg
Pauline
P
Park
Ernest
E
Rosato
Edward
E
Sauter
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001826:Body Fluids / Q000737:chemistry*; D001943:Breast Neoplasms / Q000175:diagnosis*; D016228:Endothelial Growth Factors / Q000032:analysis; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D008222:Lymphokines / Q000032:analysis; D008593:Menopause; D008875:Middle Aged; D015999:Multivariate Analysis; D009558:Nipples / Q000378:metabolism; D044469:Racial Groups; D012680:Sensitivity and Specificity; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2