High-Throughput Mutation Profiling Changes before and 3 Weeks after Chemotherapy in Newly Diagnosed Breast Cancer Patients

摘要: Background Changes in tumor DNA mutation status during chemotherapy can provide insights into biology and drug resistance. The purpose of this study is to analyse the presence or absence mutations cancer-related genes using baseline breast samples those obtained after exposure one cycle determine if any differences exist, correlate these with clinical pathological features. Methods Paired core biopsies pre- post-first doxorubicin (n = 18) docetaxel 22) treatment-naive cancer patients were analysed for 238 19 by Sequenom Oncocarta assay. Results Median age was 48 years (range 32–64); 55% had estrogen receptor-positive tumors, 60% reduction ≥25% 1. Mutations detected 10/40 (25%) pre-treatment 11/40 (28%) post-treatment samples. Four pattern categories identified based on → post-treatment: wildtype (WT)→WT, n 24; mutant (MT)→MT, 5; MT→WT, WT→MT, 6. Overall, majority tumors WT at (30/40, 75%), which 6/30 (20%) acquired new chemotherapy. Pre-treatment predominantly PIK3CA (8/10, 80%), while distributed PIK3CA, EGFR, PDGFRA, ABL1 MET. All 6 WT→MT cases treated docetaxel. Higher allele frequency MT 10; 8) correlated less 1 (R -0.667, p 0.035). No other associations observed between category treatment, clinicopathological features, response survival. Conclusion Tumor mutational profiles change as quickly cancer. Understanding changes potential therapeutic options residual resistant tumors. Trial Registration ClinicalTrials.gov NCT00212082