Circulating Tumor DNA and Survival in Metastatic Breast Cancer
Bibliographic record
Abstract
Importance: Metastatic breast cancer (MBC) poses a substantial clinical challenge despite advancements in diagnosis and treatment. While tissue biopsies offer a static snapshot of disease, liquid biopsy-through detection of circulating tumor DNA (ctDNA)-provides minimally invasive, real-time insight into tumor biology. Objective: To determine the association between ctDNA and survival outcomes in patients with MBC. Data Sources: An electronic search was performed in 5 databases (CINAHL, Cochrane Library, Embase, Medline, and Web of Science) and included all articles published from inception until October 23, 2023. Study Selection: To be included in the meta-analysis, studies had to (1) include women diagnosed with MBC; (2) report baseline plasma ctDNA data; and (3) report overall survival, progression-free survival, or disease-free survival with associated hazards ratios. Data Extraction and Synthesis: Titles and abstracts were screened independently by 2 authors. Data were pooled using a random-effects model. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, and quality was assessed using the Newcastle-Ottawa Scale. Main Outcomes and Measures: The primary study outcome was the association between detection of specific genomic alterations in ctDNA with survival outcomes. Secondary objectives were associations of study methodology with survival. Results: Of 3162 articles reviewed, 37 met the inclusion criteria and reported data from 4264 female patients aged 20 to 94 years. Aggregated analysis revealed a significant association between ctDNA detection and worse survival (hazard ratio, 1.40; 95% CI, 1.22-1.58). Subgroup analysis identified significant associations of TP53 and ESR1 alterations with worse survival (hazard ratios, 1.58 [95% CI, 1.34-1.81] and 1.28 [95% CI, 0.96-1.60], respectively), while PIK3CA alterations were not associated with survival outcomes. Stratifying by detection method, ctDNA detection through next-generation sequencing and digital polymerase chain reaction was associated with worse survival (hazard ratios, 1.48 [95% CI, 1.22-1.74] and 1.28 [95% CI, 1.05-1.50], respectively). Conclusions and Relevance: In this systematic review and meta-analysis, detection of specific genomic alterations in ctDNA was associated with worse overall, progression-free, and disease-free survival, suggesting its potential as a prognostic biomarker in MBC. These results may help guide the design of future studies to determine the actionability of ctDNA findings.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| 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".