Abstract P3-14-11: Microarray data analysis and long term outcomes of NCIC-CTG MA.22: Neoadjuvant epirubicin and docetaxel with pegfilgrastim support for locally advanced breast cancer

Abstract

Abstract Background: 93 patients were enrolled in sequential phase 1 and 2 trials of epirubicin (E) and docetaxel (D) given at 3 (cohort A) or 2 weekly (cohort B) intervals. We previously reported clinical (93%) and pathologic response rates (pCR 7%) as well as the association of fall in tumour RNA integrity (RIN) with response (ASCO 2010). Here we report the results of microarray analysis of tumor specimens pre-and mid-treatment to determine genes which are differentially expressed in different groups. Methods: 6 core biopsies were collected for all patients pre-, mid- and post-treatment with ED. 3 cores were used for standard pathologic assessment while 3 were used for gene expression assessment using Agilent full genome microarrays. Pre- and mid-treatment cores were used with Agilent Feature Extraction Software to assess microarrays; and baseline continuous (% positive) immunohistochemical ER, PR, HER2, and Topo2 were investigated by schedule and dose. RNAs with RIN > = 5.0 were subjected to microarray analysis. NIH BRB array tools were used for investigations of differential gene expressions. K-M curves were generated for the phase 2 cohorts for disease free (DFS) and event free survival (EFS), and for ER− PR− and ER or PR+ subgroups. Results: Of the 93 patients, 47 were in cohort A and 46 in cohort B. Median overall survival was 6.34 years on study. DFS at 50 months was 55% for A (phase 2) and 67% for B (phase 2), while EFS was 55% for A and 63% for B. For ER or PR+ DFS and EFS were 60% and for ER− PR− DFS and EFS were 63%. 134 arrays were available in total: 57 from A, 68 from B with 11 reference breast tumour RNAs for standardization. Patients with and without microarrays were not significantly different. Pre-treatment, we found 3 differentially expressed genes in A and 6 in B between patients who did and did not have RIN > = 5.0 at mid-treatment. Comparing CR to non-CR (PR, SD, PD), 40 genes were found for A and 2 genes for B. Many genes were also differentially expressed in A and B when analyzed by pathologic factors ER, PR, HER2, Topo2, schedule and dose. Mid-treatment, 4,365 genes in A and 18,770 genes in B were significantly different from pre-treatment. Conclusion: At 50 months, DFS was 55% for 3 weekly and 67% for 2 weekly schedules of ED. The genes identified in each cohort pretreatment will be investigated further for relevance to predicting sensitivity or resistance to E or D. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-11.