Reductions in tumor RNA integrity associated with clinical response to epirubicin/docetaxel chemotherapy in breast cancer patients.
Bibliographic record
Abstract
Abstract Abstract #6068 Background: Optimal doses and dosing intervals for neoadjuvant anthracycline/taxane chemotherapy are poorly studied. Moreover, biomarkers for measuring response to such combination regimens are unknown. This study investigated these issues in sequential phase I/II cohorts of women with locally advanced or inflammatory breast cancer treated with epirubicin and docetaxel with pegfilgrastim support at 3- or 2-weekly intervals in association with the NCIC-CTG MA.22 clinical trial. Methods: Accrual has been completed for the 3-weekly regimen (maximum tolerated dose: epirubicin 105 mg/m2, taxotere 75 mg/m2), and continues for the phase II portion of the 2-weekly regimen. Six core biopsies were obtained from 50 patients pre-, mid-, and post-treatment. Immunohistochemical staining was performed to determine baseline levels of ER, PR, HER2 and Topo II expressed as % positive stain. Tumour RNA integrity (RIN) and tumor extent were measured pre-, mid- and post-treatment by capillary electrophoresis and light microscopy after haematoxylin/eosin staining, respectively. Associations between maximum and average RIN at the three time points and tumour extent, clinical response, pathologic complete response, or baseline levels of ER, PR, HER2 and Topo II were assessed using Spearman correlation coefficients after data transformation to improve symmetry and stabilize variances. The association between both RIN and tumour extent, and baseline drug dose was assessed using a 1-way ANOVA. Results: Low mid-treatment maximum RIN was associated with high drug dose level (p=0.05) and eventual pathologic complete response (p=0.01). Post-treatment, low maximum and average RIN were found to be associated with low tumor extent (p=0.004 and p=0.01, respectively). As well, low average RIN was significantly associated with clinical complete response post-treatment (p=0.01). As expected, post-treatment low tumor extent was significantly associated with pathologic complete response (p=0.01). High pre-treatment Topo II levels were also significantly associated with high RIN (p = 0.03). No association was observed between RIN and HER2, ER or PR. Discussion: The association of RIN with tumour extent, pathologic complete response, clinical response, a known risk factor (Topo II), and drug dose suggests that the RIN may represent an important new biomarker for measuring response to anthracycline/taxane combinations (and possible other chemotherapy regimens) in breast cancer patients. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6068.
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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) | 0.001 | 0.000 |
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".