Cardiac magnetic resonance tissue biomarkers unlikely to identify cancer therapy-related cardiac dysfunction in patients with breast cancer

1. Cardiac magnetic resonance (CMR) imaging demonstrated myocardial inflammation and edema in patients with ERBB2-positive breast cancer after receiving trastuzumab.

2. Rise in CMR-identified biomarkers did not correlate with changes to ejection fraction or myocardial strain and were therefore not useful in identifying risk of cancer therapy-related cardiac dysfunction (CTRCD).

Level of Evidence Rating: 2 (Good)

Study Rundown: Cancer therapy-related cardiac dysfunction (CTRCD) refers to several patterns of myocardial injury which may result from systemic cancer treatment. Unfortunately, many of these consequences do not present until late in the disease, when treatment options are limited. New research has demonstrated some promise for noninvasive means of detecting early biomarker changes reflective of CTRCD, such as cardiac magnetic resonance (CMR) imaging. This study sought to determine the utility of CMR-detected biomarkers in diagnosing early-stage CTRCD amongst patients with ERBB2-positive breast cancer receiving systemic therapy.

Data from 136 patients were included in total. Of these, 37 patients (27%) developed CTRCD in total. Regarding inflammation detected via CMR parameters, myocardial relative enhancement peaked after anthracycline therapy from a baseline of 46% to a peak of 56.2% – elevation persisted 3 months into trastuzumab therapy. Skeletal muscle enhancement peaked later, at the 3 month time point, and diminished at study completion. No significant association was found between changes in left ventricular ejection fraction and CMR biomarker elevation.

The present study determined that while CMR is able to detect inflammatory cardiac changes in response to anthracycline and trastuzumab systemic therapy in patients with ERBB2-positive breast cancer, these markers do not correlate with early diagnosis of CTRCD. Biomarker elevation tended to occur early in therapy and was usually transient. Therefore, the clinical significance of CMR in this context is limited in the general population of ERBB2-positive breast cancer patients. This work may help identify CMR’s role in managing patients who may be more sensitive to myocardial damage from cancer therapy. A primary limitation of this study was the small sample size, particularly concerning how few patients developed the primary outcome. Future studies should seek to specifically identify biomarker changes in patients who develop CTRCD and meaningful points for intervention.

Click here to read this study in JAMA Cardiology

Relevant reading: Cancer therapy-related cardiac dysfunction: an overview for the clinician

In-Depth [prospective cohort]: A prospective cohort study was conducted at the University Health Network in Toronto, Canada. The study was titled EMBRACE-MRI: Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With Magnetic Resonance Imaging. Adult female patients diagnosed with ERBB2-positive (formerly HER2-positive) breast cancer who were to receive trastuzumab and anthracycline systemic therapy were eligible. Exclusion criteria were: contraindications to CMR or gadolinium-based contrast, life expectancy under 12 months, participation in another cancer trial, prior anthracycline therapy or preexisting myocardial disease. Patient recruitment took place between November 2013 and January 2019. All patients had 5 CMR studies performed: (1) before and (2) after anthracycline, then (3) 3 months, (4) 6 months into trastuzumab treatment and (5) after completion of therapy. CTRCD was assessed at each time point using serum biomarkers, clinical symptoms and CMR results.

37 (27%) of patients developed CTRCD: 1 after anthracycline, 14 at 3 months after trastuzumab initiation, 14 at 6 months after trastuzumab initiation, and 8 after trastuzumab completion. 10 patients required interruption of trastuzumab therapy at the time of CTRCD diagnosis, and 19 required new/increased prescriptions of cardiac medications for heart failure.  Myocardial relative enhancement peaked after anthracycline therapy from a baseline of 46% (standard deviation 16.8%) to a peak of 56.2% (18.6%) – elevation persisted 3 months into trastuzumab therapy. The only parameter associated with change to ejection fraction was extracellular volume (P = 0.009).  The findings described here were robust to sensitivity analysis.

Image: PD

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