Abstract P3-10-26: Quantitative Protein and Gene Expression Biomarkers of Tamoxifen and Letrozole Recurrence in the NCIC CTG MA.17 Cohort
Bibliographic record
Abstract
Abstract Background: The MA.17 study showed that extended adjuvant endocrine therapy with letrozole (LET) after completing 5 years of tamoxifen (TAM) markedly reduced the risk of recurrence in women with ER+ early stage breast cancer and improved overall survival in women presenting with node +ve disease. The HOXB 13:IL17BR gene expression ratio (signature) has been shown to predict outcome in breast cancer patients treated with adjuvant tamoxifen monotherapy and provides additional information beyond that from known positive (ER and PR) and negative (Her-1 and Her-2) predictors of responsiveness to tamoxifen in node-ve women. We report a case control evaluation of the Breast Cancer Index (BCI; bioTheranostics, Inc.), which combines the HOXB13 and IL17BR twogene and the molecular grade index (MGI) gene expression signatures, with respect to distinguishing which patients are at risk of late recurrences and who would respond to extended endocrine therapy with LET. The prognostic and predictive utility of quantitative immunofluorescence of ER, PR, Her-2, tumor aromatase, COX-2, GATA3 and Nat1 in the TAM-PLACEBO and the TAM-LET cohorts will also be evaluated and compared to results derived by standard immunohistochemistry. Methods: FFPE tumor blocks were collected from patients who experienced a breast cancer recurrence up to unblinding of MA.17. Controls were matched 2:1 for age, tumor size, lymph node status, and prior chemotherapy, and were all disease free for longer than cases. All cases were reviewed for standard histopathology by two independent pathologists. RNA was extracted, amplified, converted to cDNA and subjected to RT-PCR with primers and probes to HOXB13, IL17BR, BUB1A, CENPA, NEK2, RACGAP1 and RRM2. ER, PR HER1, HER2, COX2, Aromatase, GATA3 and NAT1 will be analyzed by routine IHC techniques and by immunoflourescent Automated Quantitative Analysis (AQuA). Results: 105 cases and 210 matched controls are available for evaluation. All sections are under review and tissue microarrays have been performed on all cases and controls. Detailed results on the BCI and ER, PR, Her-2 will be available at the SABCS. Discussion: MA.17 has shown that extended adjuvant endocrine therapy after tamoxifen is effective at preventing disease recurrence given for an additional 5 years. Numerous clinical trials are exploring whether extending AIs will show this benefit, and there is an increasing need to improve the therapeutic index by distinguishing those at risk from those who are not. It is also important to determine which patients will benefit from the therapy and which will recur without benefit. The latter patients could be triaged to clinical trials of novel therapies to overcome endocrine resistance. This study will help to define these issues and pave the way for more effective selection of specific patients for adjuvant endocrine strategies. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-26.
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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 | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".