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. 2023 Feb 1;6(2):e2254669.
doi: 10.1001/jamanetworkopen.2022.54669.

Association of Anthracycline With Heart Failure in Patients Treated for Breast Cancer or Lymphoma, 1985-2010

Carolyn M Larsen  1 , Mariana Garcia Arango  2 , Harika Dasari  3 , Maria Arciniegas Calle  2 , Effie Adjei  2 , Juan Rico Mesa  2 , Christopher G Scott  4 , Carrie A Thompson  5 , James R Cerhan  4 , Tufia C Haddad  6 , Matthew P Goetz  2 , Joerg Herrmann  2 , Hector R Villarraga  2
Affiliations

Association of Anthracycline With Heart Failure in Patients Treated for Breast Cancer or Lymphoma, 1985-2010

Carolyn M Larsen et al. JAMA Netw Open. .

Erratum in

  • Error in Affiliations.
    [No authors listed] [No authors listed] JAMA Netw Open. 2023 Mar 1;6(3):e234015. doi: 10.1001/jamanetworkopen.2023.4015. JAMA Netw Open. 2023. PMID: 36867413 Free PMC article. No abstract available.

Abstract

Importance: Anthracyclines increase the risk for congestive heart failure (CHF); however, long-term cumulative incidence and risk factors for CHF after anthracycline therapy are not well defined in population-based studies.

Objective: To compare the long-term cumulative incidence of CHF in patients with breast cancer or lymphoma treated with anthracycline therapy compared with healthy controls from the same community.

Design, setting, and participants: This retrospective population-based case-control study included data from the Rochester Epidemiology Project. Participants included residents of Olmsted County, Minnesota, diagnosed with breast cancer or lymphoma from January 1985 through December 2010 matched for age, sex, and comorbidities with healthy controls, with a final ratio of 1 case to 1.5 controls. Statistical analysis was performed between July 2017 and February 2022.

Exposures: Cancer treatment and CHF risk factors.

Main outcomes and measures: The main outcome was new-onset CHF, as defined by the modified Framingham criteria. Cox proportional hazards regression was used to estimate hazard ratios (HRs) to compare the risk of CHF in participants with cancer vs controls, adjusted for age, sex, diabetes, hypertension, hyperlipidemia, coronary artery disease, obesity, and smoking history.

Results: A total of 2196 individuals were included, with 812 patients with cancer and 1384 participants without cancer. The mean (SD) age was 52.62 (14.56) years and 1704 participants (78%) were female. Median (IQR) follow-up was 8.6 (5.2-13.4) years in the case group vs 12.5 (8.7-17.5) years in the control group. Overall, patients with cancer had higher risk of CHF compared with the control cohort even after adjusting for age, sex, diabetes, hypertension, coronary artery disease, hyperlipidemia, obesity, and smoking status (HR, 2.86 [95% CI, 1.90-4.32]; P < .001). After adjusting for the same variables, CHF risk was greater for patients with cancer receiving anthracycline (HR, 3.25 [95% CI, 2.11-5.00]; P < .001) and was attenuated and lost statistical significance for patients with cancer not receiving anthracyclines (HR, 1.78 [95% CI, 0.83-3.81]; P = .14). Higher cumulative incidence for patients treated with anthracyclines vs comparator cohort was observed at 1 year (1.81% vs 0.09%), 5 years (2.91% vs 0.79%), 10 years (5.36% vs 1.74%), 15 years (7.42% vs 3.18%), and 20 years (10.75% vs 4.98%) (P < .001). There were no significant differences in risk of CHF for patients receiving anthracycline at a dose of less than 180 mg/m2 compared with those at a dose of 180 to 250 mg/m2 (HR, 0.54 [95% CI, 0.19-1.51]) or at a dose of more than 250 mg/m2 (HR, 1.23 [95% CI, 0.52-2.91]). At diagnosis, age was an independent risk factor associated with CHF (HR per 10 years, 2.77 [95% CI, 1.99-3.86]; P < .001).

Conclusions and relevance: In this retrospective population-based case-control study, anthracyclines were associated with an increased risk of CHF early during follow-up, and the increased risk persisted over time. The cumulative incidence of CHF in patients with breast cancer or lymphoma treated with anthracyclines at 15 years was more than 2-fold that of the control group.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Adjei reported receiving grants from National Heart, Lung, and Blood Institute (NHLBI) during the conduct of the study. Dr Cerhan reported receiving grants from Bristol Myers Squibb, Genentech, NanoString, and Genmab; personal fees from Protagonist, and serving on an advisory board for Genentech outside the submitted work. Dr Haddad reported receiving grants (paid to Mayo Clinic) from Takeda Oncology outside the submitted work. Dr Goetz reported serving on advisory boards for ARC Therapeutics, AstraZeneca, Biotheranostics, Blueprint Medicines, Lilly, RNA Diagnostics, and Sanofi Genzyme and as a consultant for Seattle Genetics; receiving grants (paid to Mayo Clinic) from Lilly, Pfizer, and Sermonix; and personal fees from Research to Practice, Clinical Education Alliance, Medscape, MJH Life Sciences, Total Health Conferencing, and Curio Science outside the submitted work. Dr Herrmann reported receiving personal fees from Pfizer and grants from the National Institutes of Health (NIH) Natation Cancer Institute (NCI) outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Cumulative Incidence of Congestive Heart Failure (CHF) Over Time for Patients With Cancer vs Matched Comparison Cohort
Risk of CHF adjusted for age, sex, diabetes, hypertension, coronary artery disease, hyperlipidemia, obesity at baseline, and smoking history: hazard ratio, 2.86 (95% CI, 1.90-4.32); P < .001).
Figure 2.
Figure 2.. Cumulative Incidence of Congestive Heart Failure (CHF) Over Time Shown by Treatment With Anthracycline
See this image and copyright information in PMC

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