Personalized ctDNA monitoring in metastatic HR+/HER2− breast cancer patients during endocrine and CDK4/6 inhibitor therapy
Bibliographic record
Abstract
Improved methods to monitor treatment response may enhance patient management and clinical outcomes. This study assessed the feasibility and performance of a tumor-informed circulating tumor DNA (ctDNA) assay in metastatic HR+/HER2- breast cancer patients receiving endocrine and CDK4/6 inhibitor therapy. By conducting whole exome sequencing on archival tumors, highly sensitive personalized ctDNA panels were designed for blood monitoring. The assay showed high detection sensitivity (91% baseline, 70% all timepoints) and associations between higher baseline estimated variant allele fractions, liver metastases, and shorter time to treatment failure (TTF) and overall survival (OS). Complete molecular response, defined as ctDNA clearance, was observed in 28% of patients and correlated with improved TTF (HR 0.07) and OS (HR 0.07). The last cleared timepoint predated treatment failure by a median 14.3 months. ctDNA rises or limited decreases preceded radiographic progression. Molecular metrics may facilitate plasma-first monitoring and innovative strategies for clinical practice and trial design.
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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 | 0.002 |
| 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 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".