Machine Learning–Based Prediction of Distant Recurrence Risk and Ribociclib Treatment Effect in HR+/HER2− Early Breast Cancer Using Real-World and NATALEE Data
Bibliographic record
Abstract
PURPOSE: Despite current standard-of-care endocrine therapy, distant recurrence remains a concern for patients with hormone receptor-positive (HR+)/HER2- early breast cancer (EBC). Understanding individual recurrence risk would aid in clinical decision-making. We used machine learning to identify risk factors and develop recurrence risk prediction models. EXPERIMENTAL DESIGN: Predictor variables were identified by gradient boosting and used to train models on a large, diverse real-world dataset of patients with stage I-III HR+/HER2- EBC obtained from the US-based, electronic health record-derived deidentified Flatiron Health Research Database. An elastic net-penalized Cox proportional hazards model was validated internally with real-world data and externally with data from the NATALEE trial of ribociclib in patients with HR+/HER2- EBC. Prediction and outcome concordance for distant recurrence and treatment effect were analyzed with Harrell's concordance index (C-index) and integrated Brier score; model performance over time was determined by dynamic AUC analysis. RESULTS: The model accurately predicted distant recurrence in the real-world cohort [n = 7,842; C-index: 0.85 (95% confidence interval, 0.8461-0.8598); integrated Brier score: 0.05 (95% confidence interval, 0.0443-0.0495)] over time (AUC >0.7 through 10 years); internal validation and sensitivity analyses confirmed model performance. External validation with the NATALEE nonsteroidal aromatase inhibitor alone arm yielded a lower but still discriminative performance (C-index: 0.66). Training on NATALEE data improved concordance (C-index: 0.70); the NATALEE-trained model predicted a 3.2% reduction in distant recurrence at 48 months with ribociclib treatment in the real-world cohort. CONCLUSIONS: A machine learning model was developed that accurately predicted distant recurrence in HR+/HER2- EBC. The identified predictor variables and developed models may aid in risk-based personalized treatment decision-making.
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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 | 0.009 | 0.016 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| 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".