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
Bibliographic record
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".