Report on the Study of Cardiac Dysfunction Among Breast Cancer Survivors

Academic Background

Breast cancer is the most common cancer diagnosed in women. Advances in early detection and novel therapeutics have yielded 5-year survival rates exceeding 90%. However, with over four million breast cancer survivors in the United States today, the quality of survival has assumed increasing importance. Cardiovascular disease is the leading cause of mortality in patients with breast cancer who have survived ≥10 years. Patients with breast cancer exposed to cardiotoxic therapies (such as anthracyclines, trastuzumab/pertuzumab, and radiation) are at a greater risk of cardiac dysfunction compared to individuals without breast cancer.

Although previous studies have shown an association between cardiotoxic therapies and cardiac dysfunction, limited information regarding long-term risks has hindered the development of surveillance guidelines for breast cancer survivors. Therefore, this study aims to fill this knowledge gap by exploring the long-term impact of cardiotoxic therapies and cardiovascular risk factors on cardiac dysfunction among breast cancer survivors.

Source of the Paper

This paper was co-authored by Geoffrey Bostany, Yanjun Chen, Liton Francisco, Chen Dai, Qingrui Meng, Jessica Sparks, Min Sessions, Lisle Nabell, Erica Stringer-Reasor, Katia Khoury, Carrie Lenneman, Kimberly Keene, Saro Armenian, Wendy Landier, and Smita Bhatia. These authors are affiliated with the Institute for Cancer Outcomes and Survivorship, the Division of Hematology/Oncology, the Division of Cardiology, the Division of Radiation Oncology at the University of Alabama at Birmingham (UAB), and the Department of Pediatric Oncology at City of Hope. The paper was published on June 4, 2024, in the Journal of Clinical Oncology.

Research Process

Study Subjects and Screening

The study included 829 breast cancer survivors who underwent echocardiographic screening every two years after completing cardiotoxic therapy. The median age of the participants was 54.2 years, and the median follow-up period was 8.6 years. Among them, 39.7% received anthracyclines, 16% received trastuzumab/pertuzumab, 6.2% received both anthracyclines and trastuzumab/pertuzumab, and 38.1% received radiation alone.

Definition of Cardiac Dysfunction

Cardiac dysfunction was defined as a left ventricular ejection fraction (LVEF) <50% after the initiation of cardiotoxic therapy. The study categorized cardiac dysfunction into early-onset (occurring within 2 years of therapy initiation) and late-onset (occurring after 2 years).

Data Analysis

The study used Kaplan-Meier techniques to calculate the cumulative incidence of cardiac dysfunction and Cox proportional hazards models to assess the association between therapeutic exposures and cardiac dysfunction. Additionally, longitudinal analyses were conducted to explore trends in echocardiographic parameters before the onset of cardiac dysfunction.

Main Findings

Cumulative Incidence of Cardiac Dysfunction

The study evaluated 2,808 echocardiograms and found that the cumulative incidence of cardiac dysfunction increased from 1.8% at 2 years to 15.3% at 15 years after the initiation of cardiotoxic therapy. Multivariable Cox regression analysis identified non-Hispanic Black race, anthracycline exposure, selective estrogen receptor modulators (SERMs), and pre-cancer hypertension as significant risk factors for cardiac dysfunction.

Risk of Cardiac Dysfunction by Treatment Exposure

The study found that patients exposed to both anthracyclines and trastuzumab/pertuzumab had the highest risk of cardiac dysfunction (HR=3.92). Late-onset cardiac dysfunction was most prevalent among patients exposed to anthracyclines and radiation, while early-onset cardiac dysfunction was more common among those exposed to both anthracyclines and trastuzumab/pertuzumab.

Impact of Cardiovascular Risk Factors

The study also found that cardiovascular risk factors (such as hypertension, dyslipidemia, and obesity) significantly increased the risk of cardiac dysfunction. In particular, pre-cancer hypertension was associated with a three-fold higher risk of cardiac dysfunction.

Longitudinal Changes in Echocardiographic Parameters

Longitudinal analysis revealed that LVEF declined by 0.29% annually among breast cancer survivors, and this decline was evident even before the onset of cardiac dysfunction.

Conclusion

This study provides evidence supporting echocardiographic surveillance for several years after cardiotoxic therapy and highlights the importance of managing cardiovascular risk factors to mitigate the risk of cardiac dysfunction. The findings also indicate that the risk of cardiac dysfunction increases over time among breast cancer survivors exposed to cardiotoxic therapies, and cardiovascular risk factors further exacerbate this risk.

Research Highlights

1. Long-Term Risk Assessment: This study is the first to assess the long-term risk of cardiac dysfunction among breast cancer survivors in a real-world setting, filling a significant gap in the literature.
2. Identification of Risk Factors: The study identified non-Hispanic Black race, anthracycline exposure, SERMs, and pre-cancer hypertension as significant risk factors for cardiac dysfunction.
3. Importance of Early Monitoring: The results suggest that early echocardiographic monitoring can identify patients at high risk of cardiac dysfunction, providing a basis for early intervention.

Research Significance

The findings of this study have important implications for the long-term management of breast cancer survivors. The results support the need for echocardiographic surveillance for several years after cardiotoxic therapy and emphasize the importance of managing cardiovascular risk factors. Additionally, the study provides scientific evidence for the development of cardiac health monitoring guidelines for breast cancer survivors.

Other Valuable Information

The study also found that exposure to low-dose anthracyclines (≤250 mg/m²) alone increased the risk of cardiac dysfunction, even in the absence of other therapeutic exposures. This finding suggests that even low-dose anthracyclines require long-term cardiac monitoring.

This study provides critical scientific evidence for the cardiac health management of breast cancer survivors, emphasizing the importance of long-term monitoring and the management of cardiovascular risk factors.