Identification of a beta-casein-like peptide in breast nipple aspirate fluid that is associated with breast cancer.

Aims: Nipple aspirate fluid was collected prospectively from women scheduled for diagnostic breast surgery in order to determine protein masses associated with breast cancer, subsets of women with a unique proteomic profile and a breast cancer predictive model.

Materials & Methods: Breast nipple aspirate fluid was collected preoperatively in 163 breasts from 125 women and analyzed for changes in cell morphology and by SELDI-TOF mass spectrometry over approximately a 44 kDa range (1.5-45 kDa) using IMAC30, CM10 and Q10 ProteinChips.

Results: Considering all samples, 16 protein masses were associated with the presence of cancer, the most discriminating being 3592, 6570/6580 and 15870 Da. Excluding women with pathologic nipple discharge or those with a papilloma identified an additional protein of 6383 Da. The best cancer detection models included Breast Imaging Reporting and Data System, age, and either the 4262 (best sensitivity: >87%) or 3592 (best specificity: >94%) peak. MALDI-TOF mass spectrometry demonstrated the 3592 peak, which was most discriminating in many of our cancer prediction models, to be a beta-casein-like peptide.

Conclusion: Differential nipple aspirate fluid proteomic expression exists between women with/without breast cancer. The most discriminating protein identified is a beta-casein-like peptide not previously described. Combining proteomic and clinical information, which are available before surgery, optimizes the prediction of which women have breast cancer.