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September 26, 2019
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Younger breast cancer survivors at higher risk for late congestive heart failure

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Young survivors of breast cancer face higher risk for late congestive heart failure than their counterparts without cancer, according to study results published in Cancer.

“Up to now, there has been a lack of evidence about the real-world incidence and natural course of CHF [congestive heart failure] in breast cancer survivors. Previous studies were restricted to patients treated with specific regimens and had relatively small sample sizes,” Jihyoun Lee, MD, assistant professor of surgery at Soon Chun Hyang University Hospital in Seoul, South Korea, and colleagues wrote. “Other studies using claims-based data focused on high-risk older patients or overestimated the true incidence of CHF with less accurate disease diagnosis algorithms. Moreover, most previous studies focused on anthracycline-induced CHF. Thus, there are no definite guidelines about monitoring or managing other cardiac toxicity, such as myocardial infarction or myocarditis.”

In the nationwide, retrospective study, Lee and colleagues reviewed the National Health Information Database, which contains information on insurance eligibility, health examinations and medical treatment for all Korean citizens, to identify 91,227 breast cancer survivors (286,480 person-years) and 273,681 age- and sex-matched noncancer controls (884,349 person-years). Mean age of survivors and controls was 49.1 years (60.6% aged 50 years; 7.5% aged 66 years). The researchers used Cox proportional hazard regression models to assess late CHF incidence and risk factors and determined cumulative incidence rates through a Kaplan-Meier analysis and a log-rank test.

Breast cancer survivors had higher rates of prior hypertension (19.3% vs. 16.2%), diabetes (6.6% vs. 5.3%), dyslipidemia (12.2% vs. 8.3%), CHF (0.7% vs. 0.5%) and death (4.7% vs. 0.9%) than controls (P < .001 for all).

The researchers found the survivors of breast cancer incurred higher risks for late CHF than controls (HR = 1.39; 95% CI, 1.26-1.53). This risk appeared especially higher for younger survivors (aged 50 years) vs. younger controls (HR = 2.9; 95% CI, 2.42-3.47). Researchers identified older age as a risk factor for late CHF, but observed no difference in this risk between older survivors (aged 66 years) and their older counterparts (HR = 0.9; 95% CI, 0.75-1.08). Among those aged 51 to 65 years, results showed an HR for late CHF risk of 1.21 (95% CI, 1.03-1.41).

Throughout the duration of the study, survivors had a significantly higher cumulative incidence rate of CHF than controls (P < .001). This increased incidence of late CHF among survivors persisted more than 2 years after breast cancer diagnosis (P < .001).

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In evaluating use of therapeutic agents among survivors, researchers identified anthracyclines and taxanes as risk factors for late CHF, but not trastuzumab (Herceptin, Genentech), radiation or endocrine therapy.

Future studies with follow-up exceeding 5 years likely will shed more light on long-term predictors of cardiovascular risks among cancer survivors, Steven M. Ewer, MD, and David D. Pham, MD, of the division of cardiovascular medicine at University of Wisconsin School of Medicine and Public Health, wrote in a related editorial.

“Although the current study is reassuring in the sense that we are not seeing de novo late heart failure events related to trastuzumab, questions remain about those patients who do develop short-term trastuzumab cardiomyopathy and then recover,” the researchers wrote. “Do these women remain at increased risk for recurrent left ventricular dysfunction indefinitely? In which patients can we safely stop guideline-directed heart failure therapy, and which ones warrant lifelong treatment? We look forward to the answers for these and other questions in the future.” – by Jennifer Byrne

Disclosures: Lee reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Ewer and Pham report no relevant financial disclosures.