PURPOSE: To identify molecular markers of pathologic response to neoadjuvant 
paclitaxel/radiation treatment, protein and gene expression profiling were done 
on pretreatment biopsies.
EXPERIMENTAL DESIGN: Patients with high-risk, operable breast cancer were 
treated with three cycles of paclitaxel followed by concurrent 
paclitaxel/radiation. Tumor tissue from pretreatment biopsies was obtained from 
19 of the 38 patients enrolled in the study. Protein and gene expression 
profiling were done on serial sections of the biopsies from patients that 
achieved a pathologic complete response (pCR) and compared to those with 
residual disease, non-pCR (NR).
RESULTS: Proteomic and validation immunohistochemical analyses revealed that 
alpha-defensins (DEFA) were overexpressed in tumors from patients with a pCR. 
Gene expression analysis revealed that MAP2, a microtubule-associated protein, 
had significantly higher levels of expression in patients achieving a pCR. 
Elevation of MAP2 in breast cancer cell lines led to increased paclitaxel 
sensitivity. Furthermore, expression of genes that are associated with the 
basal-like, triple-negative phenotype were enriched in tumors from patients with 
a pCR. Analysis of a larger panel of tumors from patients receiving presurgical 
taxane-based treatment showed that DEFA and MAP2 expression as well as 
histologic features of inflammation were all statistically associated with 
response to therapy at the time of surgery.
CONCLUSION: We show the utility of molecular profiling of pretreatment biopsies 
to discover markers of response. Our results suggest the potential use of immune 
signaling molecules such as DEFA as well as MAP2, a microtubule-associated 
protein, as tumor markers that associate with response to neoadjuvant 
taxane-based therapy.