Association between ductal fluid proteomic expression profiles and the presence of lymph node metastases in women with breast cancer

Background. Proteomic analysis of nipple aspiration fluid (NAF) is a noninvasive method for studying the local biologic microenvironment of the breast ducts where carcinoma originates. Methods. NAF samples from each breast of 23 women with stage I or II materal invasive breast carcinoma were collected, and protein expression was analyzed comprehensively by using protein arrays and time-of-flight mass spectrometry. Blinded hierarchical clustering analysis was performed to identify potential associations between protein expression patterns and clinicopathologic factors. Results. After analysis of all spectra, 463 distinct peaks in the mass range of 7 to 30 kD were identified in NAF samples. Blinded hierarchical clustering analysis of protein expression patterns demonstrated a conservation of these patterns between the breasts of individual patients (P = .0003 X 10(12)). Hierarchical clustering revealed an association between protein expression patterns, and the presence and absolute number of axillary lymph nodes containing metastases (P = .038). Conclusions. Protein expression patterns are highly conserved between cancerous and noncancerous breasts in women with unilateral invasive breast cancer; unique expression patterns may be associated with extent of disease. High-throughput proteomic methods may reveal biologically relevant proteins involved in carcinogenesis and progression of disease.