LC-MS Tracks Heart Risk in Breast Cancer

Researchers wanted to understand how the proteins and small molecules circulating in the blood relate to changes in heart structure and function in breast cancer patients receiving heart-damaging treatments. They followed patients over time during treatment with anthracyclines and/or trastuzumab, regularly testing their blood to track these proteins and molecules, using a fast form of liquid chromatography-mass spectrometry (LC-MS) for molecular tracking. A paper based on this work was published in the European Heart Journal.¹

Why Is It Important to Understand How Cancer Treatments Affect the Heart in Breast Cancer Patients?

Heart disease and cancer are the two biggest causes of illness and death around the world.² It is well known that people with cancer face a higher risk of developing heart disease.³ This is especially true for breast cancer, the most common cancer in women worldwide, since patients often receive treatments that can harm the heart, including anthracyclines, HER2-targeted drugs, radiation, and hormone therapies.^4-6 in addition, how much a patient's heart is affected by cancer treatment depends on their individual risk factors, such as their age, other heart-related risk factors (like high blood pressure, high cholesterol, diabetes, and obesity), and whether they already have heart disease (such as clogged arteries, heart failure, irregular heartbeat, or a history of stroke).⁷ In the opinion of the researchers, however, there is no full understanding of what occursat a biological level when these cancer treatments affect the heart, or how to use that understanding to identify, ahead of time, which patients are most likely to develop heart problems or harmful changes in heart shape and structure.¹

How Did the Researchers Study the Link Between Blood Proteins/Metabolites and Heart Function, and What Did They Find?

For this study, the researchers used statistical models to see how repeated blood measurements of individual proteins or metabolites related to heart ultrasound (echocardiogram) results — both at the same visit and at later visits. These heart measurements included the size of the heart's main pumping chamber, the size of a nearby chamber, how well the heart pumps blood out, how the heart muscle stretches and squeezes, and how well the heart and blood vessels work together. For any proteins or metabolites that showed a meaningful link to heart function, the researchers ran additional analyses to see how they related to risk over time and which biological processes they were connected to.¹

Among the pool of 547 breast cancer patients (with a typical age of 50) involved in the study, the researchers found 203 different proteins and 16 different small molecules in the blood that were linked to heart structure and function, both at the same time as testing and at later checkups. One protein, cathepsin C, stood out. It was connected to how well the heart pumps blood, how the heart muscle stretches and squeezes, and the size of a heart chamber. People with higher levels of this protein were also less likely to develop heart problems later (specifically, a significant drop in pumping ability). Looking more broadly, the 147 proteins tied to heart function were involved in processes related to how cells break down and recycle proteins, as well as broader metabolic activity. Several individual small molecules were also strongly linked to heart function, including a handful of amino acids and small protein fragments.¹

“These findings,” write the authors of the paper,¹ “provide translational insights into cancer therapy-related cardiac dysfunction and remodeling and identify potential new biomarkers of cardiotoxicity. There is an important need for validation of these findings and a deeper understanding of the biology of these biomarkers.”

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References

1. Ky, B.; Xia, C.; Ko, K. et al. Cardiac Remodelling and Dysfunction in Cancer Patients Receiving Cardiotoxic Therapies: Proteomic and Metabolomic Profiling. Eur Heart J. 2026, ehag487. DOI: 10.1093/eurheartj/ehag487
2. Bray, F.; Laversanne, M.; Sung, H. et al. Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2024, 74 (3), 229-263. DOI: 10.3322/caac.21834
3. Leong, D. P.; Waliany, S.; Abdel-Qadir, H. et al.Cardiovascular Considerations During Cancer Therapy: Gaps in Evidence and JACC: CardioOncology Expert Panel Recommendations. JACC CardioOncol. 2024, 6 (6), 815-834. DOI: 10.1016/j.jaccao.2024.06.005
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5. Waliany, S.; Caswell-Jin, J.; Riaz, F. et al. Pharmacovigilance Analysis of Heart Failure Associated With Anti-HER2 Monotherapies and Combination Regimens for Cancer. JACC CardioOncol. 2023, 5 (1), 85-98. DOI: 10.1016/j.jaccao.2022.09.007
6. Dent, S. F.; Moore, H.; Raval, P. et al. How to Manage and Monitor Cardiac Dysfunction in Patients With Metastatic HER2-Positive Breast Cancer. JACC CardioOncol. 2022, 4 (3), 404-408. DOI: 10.1016/j.jaccao.2022.06.002
7. Wadden E, Vasbinder A, Yogeswaran V. et al. Life's Essential 8 and Incident Cardiovascular Disease in U.S. Women With Breast Cancer. JACC CardioOncol. 2024, 6 (5), 746-757. DOI: 10.1016/j.jaccao.2024.07.008