1. Froelich, Warren

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While heart failure is rare among young adults, cancer patients diagnosed between the ages of 18 and 39 commonly treated with anthracycline may have greater than 3 times the risk for developing this life-threatening ailment compared to young cancer survivors who were not exposed to this chemotherapeutic drug.

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The risk of increased heart failure increased as early as 2 years following treatment with anthracycline, and remained for at least 5 years after therapy, according to a study presented during the American Association for Cancer Research (AACR) Annual Meeting held April 10-15, 2021.


"We saw significant increased risk of heart failure in the population and this persisted after adjustment for common co-variants, including those of common co-morbidities that increased the likelihood of heart failure," said Elizabeth Hibler, PhD, Assistant Professor of Preventive Medicine at Northwestern University's Feinberg School of Medicine in Chicago, who presented the results.


"As a cancer epidemiologist learning about the long-term effects of cancer treatment on survivors, I was surprised that the risk of heart failure among young adult survivors had not been extensively studied," Hibler added. "As early-onset cancer increases, I believe that we must increase awareness of the potential cardiovascular effects of cancer treatment among young and emerging adults."

Elizabeth Hibler, Ph... - Click to enlarge in new windowElizabeth Hibler, PhD. Elizabeth Hibler, PhD

Chemotherapies with anthracycline are commonly used to treat a variety of cancers, including breast, leukemia, lymphoma, sarcoma or bone, and kidney. But these same lifesaving treatments also carry with them toxic effects on the heart that, in some cases, can trigger congestive heart failure or simply heart failure-a serious condition that affects the heart's ability to pump enough blood to meet the body's needs.


Previous findings from the Childhood Cancer Survivor Cohort Study demonstrated that childhood cancer survivors under age 18 treated with cardiotoxic chemotherapies, such as anthracycline, were nearly 6 times as likely to be diagnosed with heart failure when compared to their healthy siblings.


Until now, researchers did not know the long-term risk of heart failure among young and emerging adults (YEA) diagnosed between 18 and 39 years of age treated with anthracycline chemotherapies. Each year, an estimated 70,000 cancer cases are diagnosed among this population in the United States, with cancer among the top five leading causes of death.


"This study adds to the body of literature demonstrating increased risk of heart failure among childhood cancer survivors, with subclinical damage occurring at even lower treatment doses," said Hibler.


Research Details

For this study, researchers retrospectively tracked heart failure cases among patients from the Northwestern Medicine Enterprise Data Warehouse, the university's electronic health record repository. Some 12,879 patients, between ages 18 and 39 years, were diagnosed with cancer in the Northwestern Hospital system between years 2000 and 2019. Cancer types were categorized by those most commonly treated with anthracycline treatment, including breast, leukemia, lymphoma, sarcoma or bone, and kidney versus those who likely received a different therapy. Statistical analysis used Kaplan Meier and Cox proportional hazard models.


The mean age of the cohort was about 31.5 years; some 65 percent of the population were female and 68 percent were categorized as White. Cardiovascular co-morbidities were present in less than 5 percent of cancer survivors, consisting of hypertension, diabetes, and cardiovascular disease. Also included in the analysis were body mass index and reports of secondary cancers. The cohort was then stratified for specific cancer type, comparing cancers not likely to be treated with anthracycline based on tumor type to those likely to be treated with this chemotherapeutic drug.


During a median follow-up period of 3.4 years, some 180 patients in this cohort were identified with heart failure. Results showed that some 1.4 percent of patients experienced heart failure 2 years following treatment with anthracycline, compared to 0.5 percent of patients who likely did not receive anthracycline. Five years following treatment with anthracycline, about 2.4 percent of patients were diagnosed with heart failure, compared to 0.6 percent for those who likely did not receive anthracycline.


When adjusted for lifestyle and other cardiac comorbidities, the results showed that treatment with anthracycline among this young adult population increased the risk of heart failure by about 3.34-fold to 3.46-fold.


In an interview, Hibler said that many young adult cancer survivors may experience higher rates of depression, hopelessness, anxiety, and poorer self-image, all contributing to an increased likelihood of engaging in unhealthy behaviors such as smoking and illicit drug use, poor diet, and inactivity.


"These behaviors may contribute to an unexpectedly poor cardiovascular disease risk profile compared to healthy young adults," she said. "We would want physicians and patients to be aware that unhealthy behaviors may act synergistically with cancer chemotherapy to increase risk of cardiovascular disease or heart failure.


"Being aware of the risk factors means that we can mitigate long-term effects and intervene to reduce risk of heart failure among young adult survivors of cancer."


Researchers are actively investigating approaches to lessen or prevent heart damage from cancer treatments. One trial-sponsored by the National Cancer Institute and the National Heart, Lung, and Blood Institute-is testing the cholesterol-lowering medication atorvastatin for reducing heart damage in women with breast cancer who are receiving anthracycline treatment. Other heart medications, including those that lower blood pressure, also are being investigated.


Future studies will combine data collected in medical records with surveys on health behaviors related to cardiovascular disease and cancer.


"Ongoing work focuses on longitudinal studies of cancer survivorship among young and emerging adults where we will collect more detail on chemotherapies or other cancer treatments, including dose," Hibler said. "We will also recruit and collect data from healthy control populations and older cancer survivors. This will allow us to compare risk of heart failure across the life course."


Warren Froelich is a contributing writer.