Cardiac and cardiometabolic phenotyping of trastuzumab-mediated cardiotoxicity: a secondary analysis of the MANTICORE trial
Bibliographic record
Abstract
AIMS: An improved understanding of the pathophysiology of trastuzumab-mediated cardiotoxicity is required to improve outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We aimed to characterize the cardiac and cardiometabolic phenotype of trastuzumab-mediated toxicity and potential interactions with cardiac pharmacotherapy. METHODS AND RESULTS: This study was an analysis of serial magnetic resonance imaging (MRI) and circulating biomarker data acquired from patients with HER2-positive early-stage breast cancer participating in a randomized-controlled clinical trial for the pharmaco-prevention of trastuzumab-associated cardiotoxicity. Circulating biomarkers (B-type natriuretic peptide, troponin I, MMP-2 and -9, GDF-15, neuregulin-1, and IGF-1) and MRI of cardiac structure and function and abdominal fat distribution were acquired prior to trastuzumab, post-cycle 4 and post-cycle 17. Ninety-four participants (51 ± 8 years) completed the study with 30 on placebo, 33 on perindopril, and 31 on bisoprolol. Post-cycle 4, global longitudinal strain deteriorated from baseline in both placebo (+2.0 ± 2.7%, P = 0.002) and perindopril (+0.9 ± 2.5%, P = 0.04), but not with bisoprolol (-0.2 ± 2.1%, P = 0.55). In all groups combined, extracellular volume fraction and GDF-15 increased post-cycle 4 (+1.3 ± 4.4%, P = 0.004; +130 ± 150%, P ≤ 0.001, respectively). However, no significant change in troponin I was detected throughout trastuzumab. In all groups combined, visceral and intermuscular fat volume increased post-cycle 4 (+7 ± 17%, P = 0.02, +8 ± 23%, P = 0.02, respectively), while muscle volume and IGF-1 decreased from post-cycle 4 to 17 (-2 ± 10%, P = 0.008, -18 ± 28%, P < 0.001, respectively). CONCLUSION: Trastuzumab results in impaired cardiac function and early myocardial inflammation. Trastuzumab is also associated with deleterious changes to the cardiometabolic phenotype which may contribute to the increased cardiovascular risk in this population.
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 | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.006 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".