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Chemotherapy and heart failure

Patients with a diagnosis of breast cancer or lymphoma who received chemotherapy treatment might be at risk of long-term side effects. We evaluated the association between a type of chemotherapy, called anthracyclines, and the risk of developing heart failure in patients with cancer. In this study, patients treated with anthracycline were more likely to have heart failure compared to controls.

Credits: Fernando Zhiminaicela ©
by Hector Villarraga | Associate Professor

Hector Villarraga is Associate Professor at Mayo Clinic.

, Mariana Garcia Arango | Associate Professor

Mariana Garcia Arango is Associate Professor at .

Edited by

Alba Covelo Paz

Junior Scientific Editor

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published on Mar 25, 2024
One of the chemotherapy treatment options for patients with breast cancer usually includes multiple cycles of therapies based on an intravenous medication of a group called anthracyclines. During the last two decades, the percentage of cure and response rates for cancer patients undergoing this treatment have improved significantly, increasing survivorship and, in turn, the number of patients who have received chemotherapy. 

Anthracyclines work by altering cancer cells, genes, causing malfunction. These effects are relevant for cancer treatment; however, one of the potential side effects of anthracyclines is the development of heart failure. In previous studies, anthracycline's toxic effect on the heart has been described as dose-dependent, meaning a higher dose was associated with higher cardiac risks. 

We completed a study that focused on evaluating the risk of developing heart failure in cancer patients treated with anthracyclines compared to individuals with similar age and cardiac risk factors from the same region who did not receive this medication (referred to as controls). The study population was located in the midwest of the United States and is part of the Rochester Epidemiology Project (REP) network, which allowed for accurate recollection of information by clinicians and cardiologists. 

We assessed 2,196 patients in total, including 812 with breast cancer, Hodgkin and non-Hodgkin lymphoma, and controls. We evaluated the total number of patients who developed heart failure for over 20 years. Interestingly, cancer patients generally had a higher associated risk of heart failure than controls. To address the connection with anthracyclines, we evaluated a subset of patients, comparing anthracycline use to no anthracycline. Those who received an anthracycline-based regimen had an increased risk of developing heart failure. This risk started during the first year of treatment and persisted throughout the 20 years of follow-up, and was present regardless of the dose, even with low to intermediate dosage. 

The cumulative incidence evaluates the number of patients at risk that developed heart failure during a specific time. This cumulative incidence showed that patients with anthracycline use had more than double risk of developing heart failure after 20 years, compared to cancer patients with no anthracycline use. 

In our study, we evaluated what other conditions might be associated with increasing the risk of developing heart failure in this patient population. We identified the age of diagnosis as an important consideration. Other risk factors, such as high cholesterol, diabetes mellitus, hypertension, or the concomitant use of radiotherapy regimens, were not significantly associated with a higher risk of heart failure. 

Patients with breast cancer or lymphoma (Hodgkin or non-Hodgkin) have a significantly greater risk of developing heart failure (10.75% vs 4.98% for controls) up to 20 years after the diagnosis of their malignancy, and this is associated with the use of anthracycline chemotherapy. 

To summarize, this study contributes to expanding the current literature, supporting, and creating guidelines for patients undergoing a chemotherapy regimen based on anthracyclines. Our goal is the close monitoring and time-efficient identification of signs and symptoms of cardiotoxicity, to prevent further damage. Patients should be frequently screened for symptoms such as shortness of breath, fatigue, and lower extremity edema. Additionally, imaging such as echocardiography (cardiac ultrasound), cardiac MRI, or stress tests should be implemented periodically to identify early deterioration of cardiac function. 
Original Article:
Larsen CM, Garcia Arango M, Dasari H, Arciniegas Calle M, Adjei E, Rico Mesa J, Scott CG, Thompson CA, Cerhan JR, Haddad TC, Goetz MP, Herrmann J, Villarraga HR. Association of Anthracycline With Heart Failure in Patients Treated for Breast Cancer or Lymphoma, 1985-2010. JAMA Netw Open. 2023 Feb 1;6(2):e2254669. doi: 10.1001/jamanetworkopen.2022.54669. Erratum in: JAMA Netw Open. 2023 Mar 1;6(3):e234015. PMID: 36735254; PMCID: PMC9898820.

Edited by:

Alba Covelo Paz , Junior Scientific Editor

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