Mechanisms of Exercise Intolerance Across the Breast Cancer Continuum: A Pooled Analysis of Individual Patient Data
Bibliographic record
Abstract
PURPOSE: The purpose of this study is to evaluate the prevalence of abnormal cardiopulmonary responses to exercise and pathophysiological mechanism(s) underpinning exercise intolerance across the continuum of breast cancer (BC) care from diagnosis to metastatic disease. METHODS: Individual participant data from four randomized trials spanning the BC continuum ([1] prechemotherapy [n = 146], [2] immediately postchemotherapy [n = 48], [3] survivorship [n = 138], and [4] metastatic [n = 47]) were pooled and compared with women at high-risk of BC (BC risk; n = 64). Identical treadmill-based peak cardiopulmonary exercise testing protocols evaluated exercise intolerance (peak oxygen consumption; V̇O2peak) and other resting, submaximal, and peak cardiopulmonary responses. The prevalence of 12 abnormal exercise responses was evaluated. Graphical plots of exercise responses were used to identify oxygen delivery and/or uptake mechanisms contributing to exercise intolerance. Unsupervised, hierarchical cluster analysis was conducted to explore exercise response phenogroups. RESULTS: Mean V̇O2peak was 2.78 ml O2.kg-1·min-1 (95% confidence interval [CI], -3.94, -1.62 mL O2.kg-1·min-1; P < 0.001) lower in the pooled BC cohort (52 ± 11 yr) than BC risk (55 ± 10 yr). Compared with BC risk, the pooled BC cohort had a 2.5-fold increased risk of any abnormal cardiopulmonary response (odds ratio, 2.5; 95% confidence interval, 1.2, 5.3; P = 0.014). Distinct exercise responses in BC reflected impaired oxygen delivery and uptake relative to control, although considerable inter-individual heterogeneity within cohorts was observed. In unsupervised, hierarchical cluster analysis, six phenogroups were identified with marked differences in cardiopulmonary response patterns and unique clinical characteristics. CONCLUSIONS: Abnormal cardiopulmonary response to exercise is common in BC and is related to impairments in oxygen delivery and uptake. The identification of exercise response phenogroups could help improve cardiovascular risk stratification and guide investigation of targeted exercise interventions.
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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 | 0.025 | 0.045 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.008 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| 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".