NEW ORLEANS – While increasingly effective at treating cancer, commonly used therapies, such as chemotherapy and radiation, increase a patient’s risk of experiencing a decline in cardiac function. This decline can interfere with cancer treatment or lead to severe heart disease. At the American College of Cardiology’s 68th Annual Scientific Session, researchers from the Perelman School of Medicine at the University of Pennsylvania presented findings from two studies that examined changes in cardiovascular biomarkers upon a patient’s exposure to cancer treatment to determine whether blood tests could serve as viable predictors for identifying who may be at a heightened risk for cardiotoxicity.
Using Blood Tests to Predict One’s Risk of Cardiac Dysfunction Following Exposure to Commonly Used Cancer Therapies
Research has shown that two widely used and effective treatments for breast cancer – doxorubicin and trastuzumab – can increase a patient’s risk of cardiac dysfunction and heart failure, particularly when they are used in combination. However, there are no comprehensive methods for identifying which patients will experience adverse cardiac outcomes.
To determine whether biomarkers can help identify patients at a heightened risk, Penn researchers examined the correlation over time between changes in five biomarkers and changes in ejection fraction – the percentage of blood leaving one’s heart with each contraction – among 323 patients who were treated with one or both of the therapies. The data revealed a strong correlation between changes in one of the blood tests, NT-proBNP, and a lower ejection fraction, particularly in patients treated with anthracycline, then trastuzumab. Researchers also found that another blood test, MPO, was a predictor of cardiotoxicity in breast cancer patients treated with a anthracycline-based therapy regimen.
“Our data supports a role for biomarkers in the monitoring of cardiac dysfunction in breast cancer patients during treatment, particularly the subgroup of patients receiving sequential doxorubicin and trastuzumab therapy,” said Bonnie Ky, MD, MSCE, an associate professor of Cardiovascular Medicine and Epidemiology. “Overall, this suggests that these blood tests could potentially be used as markers of cardiotoxicity. However, additional research is needed to determine the clinical impact of biomarker monitoring on ultimate cardiovascular and oncologic outcomes.”
The work was supported by the National Heart, Lung and Blood Institute (R01-HL-118018); the Perelman School of Medicine’s McCabe Fellow Award; American Cancer Society’s Institutional Research Grant (78-002-30), a grant from the National Heart, Lung and Blood Institute (K23-HL095661); and an investigator initiated award from Roche Diagnostics.
Early Changes in Cardiovascular Biomarkers with Contemporary Thoracic Radiation Therapy for Breast Cancer, Lung Cancer and Mediastinal Lymphoma
While cardiotoxicity most often occurs more than five years after treatment, research has shown that subclinical changes, including structural and functional abnormalities in the heart, may occur shortly after radiation exposure.
To better understand the development of radiation therapy-induced heart disease, and to describe the changes that occur following treatment, a team of Penn researchers examined early changes in patients’ cardiovascular biomarkers that would indicate heart damage or stress following exposure to radiation therapy. Then, researchers evaluated the correlation between the dose of radiation to the heart and the changes in biomarker levels. Data revealed that radiation therapy induces acute abnormalities in vascular and inflammatory biomarkers that are associated with mean heart dose (MHD) – particularly in lung cancer and mediastinal lymphoma.
“The data suggest that these pathways of microvascular dysfunction and inflammation could be important in the development of radiation-induced heart disease,” said Biniyam G. Demissei, MD, a postdoctoral fellow. “Additional research is needed to determine if these biomarkers can serve as predictors of clinical cardiotoxicity in patients exposed to radiation.”
This work was supported by the National Heart, Lung and Blood Institute (R01-HL-118018); a pilot grant award from Penn Medicine’s Abramson Cancer Center and Radiation Oncology; and an investigator initiated award from Roche Diagnostics.
Editor’s Note: Dr. Ky serves as a consultant to Roche and receives research funding from the company. Dr. Liu also receives research funding from Roche.
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