Cardiovascular toxicities in patients with triple negative breast cancer receiving treatment with chemotherapy and immunotherapy
Bibliographic record
Abstract
Abstract Background Triple-negative breast cancer (TNBC) is an aggressive subtype accounting for ~15% of breast cancers. Data demonstrates improved survival using a combination of immune checkpoint inhibitors (ICIs) and chemotherapy. While anthracyclines and ICIs individually pose cardiovascular risks, data on their combined cardiotoxic effects are limited. Methods This ongoing prospective observational study monitors TNBC patients receiving curative-intent anthracyclines and ICIs using a standardized protocol (Figure 1). Surveillance includes clinical assessments, echocardiography, and cardiac biomarkers at predefined time points. We present preliminary data from the first 37 enrolled patients. Results The mean ± SD age at diagnosis was 53 ± 13 years. Baseline comorbidities included hypertension (24.3%), dyslipidemia (35.1%), diabetes (10.8%), ischemic heart disease (5.4%), hypothyroidism (18.9%), and other autoimmune disease (5.4%). Five patients (13.5%) had prior cancer with anthracycline exposure. Baseline echocardiograms showed normal LVEF (62.4±4.3%) and GLS (n=25) -19.8±2.5%. Baseline troponin levels (n=34) were all normal. Twenty two patients (59.5%) completed the neoadjuvant regimen. Pembrolizumab was discontinued in 11 (29.7%) and doxorubicin in 5 (13.5) due to toxicities. Two (5.4%) patients declined anthracyclines, leading to concurrent pembrolizumab omission. ICI-associated toxicities occurred in 17/37 (45.9%) patients including 2 (5.4%) cases of grade 1 myocarditis (confirmed by CMR). Other immune-related events included thyroiditis (n=5), hepatitis (n=3), dermatitis (n=2), adrenal insufficiency (n=2), hypophysitis (n=1), and sudden hearing loss (n=1). Eight patients received corticosteroids. Post-anthracycline echocardiograms (available in n=32) showed 2D LVEF of 57.7± 4.2 (baseline 62.0±4.2%), with asymptomatic CTRCD in 8/32 (25%) patients (mild CTRCD in 6 and moderate in 2), and an elevated high-sensitivity troponin (>99th percentile) in 14/32 (43.8%). Adjuvant pembrolizumab was initiated in 12/37 patients (32.4%). The main reasons for omission were prior ICI toxicity (21.6%), residual disease requiring alternative treatment (18.9%), and complete pathological response (16.2%). Three patients (25%) discontinued adjuvant pembrolizumab due to non-cardiovascular ICI-related toxicity. Conclusion In this preliminary report of a cohort study of women with TNBC receiving ICIs and anthracyclines, cardiovascular events were common and included myocarditis in 5.4%, abnormal troponin in 43.8%, and CTRCD in 25% (mostly mild). These findings may be due to prospective surveillance identifying low-grade (asymptomatic) myocarditis/injury and/or a chance finding due to small sample size. Our preliminary findings highlight the need for continued monitoring and larger studies to better understand cardiovascular risks in patients receiving a combination of ICIs and anthracyclines.
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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".