Improved diagnostic screening has led to earlier detection of many tumors, but 
screening may still miss many aggressive tumor types. Proteomic and genomic 
profiling studies of breast cancer samples have identified tumor markers that 
may help improve screening for more aggressive, rapidly growing breast cancers. 
To identify potential blood-based biomarkers for the early detection of breast 
cancer, we assayed serum samples via matrix-assisted laser desorption 
ionization-time of flight mass spectrometry from a rat model of mammary 
carcinogenesis. We found elevated levels of a fragment of the protein dermcidin 
(DCD) to be associated with early progression of N-methylnitrosourea-induced 
breast cancer, demonstrating significance at weeks 4 (p = 0.045) and 5 (p = 
0.004), a time period during which mammary pathologies rapidly progress from 
ductal hyperplasia to adenocarcinoma. The highest serum concentrations were 
observed in rats bearing palpable mammary carcinomas. Increased DCD was also 
detected with immunoblotting methods in 102 serum samples taken from women just 
prior to breast cancer diagnosis. To validate these findings in a larger 
population, we applied a 32-gene in vitro DCD response signature to a dataset of 
295 breast tumors and assessed correlation with intrinsic breast cancer subtypes 
and overall survival. The DCD-derived gene signature was significantly 
associated with subtype (p < 0.001) and poorer overall survival [HR (95 % CI) = 
1.60 (1.01-2.51), p = 0.044]. In conclusion, these results present novel 
evidence that DCD levels may increase in early carcinogenesis, particularly 
among more aggressive forms of breast cancer.