HER2 status and prediction of extended endocrine benefit with breast cancer index (BCI) in HR+ patients in the adjuvant tamoxifen: To offer more? (aTTom) trial.
Bibliographic record
Abstract
522 Background: BCI is a validated gene expression-based assay that stratifies patients based on risk of overall (0-10y) and late (post-5y) distant recurrence (DR) and predicts likelihood of benefit from extended endocrine therapy (EET). The Trans-aTTom study established Level1B validation for BCI (H/I) to predict benefit from EET.1 In this updated Trans-aTTom analysis including HER2 status, BCI (H/I) and prediction of endocrine benefit were further characterized. Methods: Centralized HER2 was determined for all cases according to current ASCO/CAP guidelines. Kaplan-Meier and Cox proportional hazards regression were conducted to assess primary and secondary endpoints of Recurrence-Free Interval (RFI) and Disease-Free Interval (DFI), respectively. A three-way interaction using likelihood ratio testing, which included treatment, BCI (H/I) and HER2, was performed to assess the effect of HER2 on BCI (H/I) prediction of EET benefit. Results: Of 789 N+ patients, 90% (N = 711) and 9% (N = 72) were HR+/HER2- and HR+/HER2+, respectively. In the HER2- subset, BCI (H/I)-High (48%) showed significant benefit from 10y vs. 5y of tamoxifen (9.4% RFI: HR = 0.35 [95% CI 0.15-0.81]; P = 0.047) while BCI (H/I)-Low patients did not (-2.1% RFI; HR = 1.15 [95% CI 0.78-1.69]; P = 0.491). For DFI, BCI (H/I)-High patients also showed significant benefit (10.3% DFI; HR = 0.41 [95% CI 0.18-0.91]; P = 0.047) while BCI (H/I)-Low patients did not (-1.7% DFI; HR = 1.10 [95% CI 0.75-1.62] P = 0.612). As demonstrated in the overall N+ cohort, significant interaction between BCI (H/I) and treatment was shown in the HER2- subset (RFI P = 0.045; DFI P = 0.044). Notably, three-way interaction evaluating BCI (H/I), treatment and HER2 status was not statistically significant (P = 0.85), indicating the ability of BCI (H/I) to predict benefit of EET activity was not significantly affected by HER2 status. Conclusions: In this updated Trans-aTTom analysis with HER2 data, BCI (H/I) showed similar predictive performance for EET response in the HER2- subset when compared to the overall N+ cohort. These data further support the clinical utility of BCI (H/I) as a predictive biomarker for informing EET benefit in HR+/HER2- and HR+/HER2+ disease. Clinical trial information: NCT00003678 . [Table: see text]
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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 | 0.002 | 0.001 |
| 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 | 0.001 |
| 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".