A comparative study of survival models for breast cancer prognostication revisited: the benefits of multi-gene models
Bibliographic record
Abstract
BACKGROUND: The development of clinical -omic biomarkers for predicting patient prognosis has mostly focused on multi-gene models. However, several studies have described significant weaknesses of multi-gene biomarkers. Indeed, some high-profile reports have even indicated that multi-gene biomarkers fail to consistently outperform simple single-gene ones. Given the continual improvements in -omics technologies and the availability of larger, better-powered datasets, we revisited this "single-gene hypothesis" using new techniques and datasets. RESULTS: By deeply sampling the population of available gene sets, we compare the intrinsic properties of single-gene biomarkers to multi-gene biomarkers in twelve different partitions of a large breast cancer meta-dataset. We show that simple multi-gene models consistently outperformed single-gene biomarkers in all twelve partitions. We found 270 multi-gene biomarkers (one per ~11,111 sampled) that always made better predictions than the best single-gene model. CONCLUSIONS: The single-gene hypothesis for breast cancer does not appear to retain its validity in the face of improved statistical models, lower-noise genomic technology and better-powered patient cohorts. These results highlight that it is critical to revisit older hypotheses in the light of newer techniques and datasets.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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) | 0.000 | 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 teacher head, 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".