Anuradha Chakravarthy
Faculty Member
Last active: 3/30/2020

Identification of markers of taxane sensitivity using proteomic and genomic analyses of breast tumors from patients receiving neoadjuvant paclitaxel and radiation.

Bauer JA, Chakravarthy AB, Rosenbluth JM, Mi D, Seeley EH, De Matos Granja-Ingram N, Olivares MG, Kelley MC, Mayer IA, Meszoely IM, Means-Powell JA, Johnson KN, Tsai CJ, Ayers GD, Sanders ME, Schneider RJ, Formenti SC, Caprioli RM, Pietenpol JA
Clin Cancer Res. 2010 16 (2): 681-90

PMID: 20068102 · PMCID: PMC2892225 · DOI:10.1158/1078-0432.CCR-09-1091

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.

MeSH Terms (18)

Biomarkers, Pharmacological Breast Neoplasms Carcinoma Combined Modality Therapy Drug Resistance, Neoplasm Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Genomics Genomics Humans Metabolome Neoadjuvant Therapy Oligonucleotide Array Sequence Analysis Paclitaxel Proteomics Taxoids Tumor Cells, Cultured

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