Prognostic and Predictive Impact of Intrinsic Biological Classification by Immunohistochemistry (IHC) and QPCR for Adjuvant Tamoxifen in Pre-Menopausal Breast Cancer: Results from the NCIC CTG MA.12 Trial.
Bibliographic record
Abstract
Abstract Background: Aside from the estrogen receptor (ER), there is no other validated predictive biomarker for the magnitude of benefit from tamoxifen. Gene expression profiling has clearly demonstrated that breast cancer is a heterogeneous disease, and has re-classified breast cancer into intrinsic subtypes. We have utilized material from a prospective randomized trial of tamoxifen versus placebo in pre-menopausal women with primary breast cancer who have completed adjuvant chemotherapy (NCIC CTG MA.12 Trial) in order to evaluate the prognostic and predictive significance of intrinsic subtypes as classified by both IHC and qPCR.Methods: A tissue microarray (TMA) was constructed from 492/672 (72%) of the study population. A panel of six IHC antibodies (ER, PR, HER2, EGFR, CK 5/6 and Ki67) was utilized with established cut-offs to define the intrinsic subtypes of luminal A, luminal B, HER-2 and basal. Total RNA from 403/672 (60%) patients was sufficient for intrinsic subtyping with a 50 gene predictor (PAM50) by qPCR. In 354 cases intrinsic subtyping was performed by both methods.Results: There were no significant differences between the initial study population and the TMA series in baseline characteristics. Within the TMA series 39% (n=190) were classified as luminal A, 31% luminal B (n=143) [20% by Ki67 and 11% by HER2], 7% HER2-enriched and 17% basal-like by IHC. Intrinsic subtypes were prognostic with luminal A (5 year 93% OS) having the best outcome and basal-like (5 year 71% OS) the worst (p=0.0086 Wilcoxon). Tamoxifen appeared to benefit the luminal B cancers most (5 year DFS HR 0.67; 95% CI 0.39-1.16: p=0.077) when compared to placebo, however no subtype, nor ER status alone, predicted benefit of tamoxifen in this correlative study. Data for concordance for subtyping by IHC and qPCR as well as prognostic/predictive impact by qPCR subtyping will be presented.Conclusions: Intrinsic biological classification of breast cancer is important for prognosis and may have predictive value for relative benefit to tamoxifen. Further validation of these results are required. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4056.
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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 | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".