Strahlentherapie und Onkologie

, Volume 195, Issue 7, pp 629–639 | Cite as

Risk of cardiotoxicity induced by adjuvant anthracycline-based chemotherapy and radiotherapy in young and old Asian women with breast cancer

  • Chih-Hsin Lee
  • Jun-Fu Zhang
  • Kevin Sheng-Po Yuan
  • Alexander T. H. Wu
  • Szu-Yuan WuEmail author
Original Article



The risk of cardiotoxicity induced by adjuvant anthracycline-based chemotherapy (CT) and radiotherapy (RT) is yet to be investigated in a large-scale randomized controlled trial with an adequate sample size of young and old women with breast cancer.

Patients and methods

To compare the occurrence of major heart events (heart failure and coronary artery disease) in patients with breast cancer, 3489 women who underwent surgical resection of the breast tumor were retrospectively selected from the Taiwan National Health Insurance Research Database. The patients were categorized into the following groups based on their treatment modalities: group 1 (n = 1113), no treatment; group 2 (n = 646), adjuvant RT alone; group 3 (n = 705), adjuvant anthracycline-based CT alone; and group 4 (n = 1025), combined adjuvant RT and anthracycline-based CT.


The mean patient age was 50.35 years. Subsequent coronary artery disease and heart failure were identified in 244 (7.0%) and 206 (5.9%) patients, respectively. All three adjuvant therapies were significant independent prognostic factors of major heart events (adjusted hazard ratio [95% confidence interval]: 1.47 [1.24–1.73]; 1.48 [1.25–1.75], and 1.92 [1.65–2.23] in groups 2, 3, and 4, respectively). In patients aged ≥50 years with breast cancer who underwent surgery, the log-rank p values of groups 2 and 3 after adjustment were 0.537 and 0.001, respectively.


Adjuvant RT can increase cardiotoxicity in patients with breast cancer, particularly when used in combination with anthracycline-based CT. Therefore, it should be offered with optimal heart-sparing techniques, particularly in younger patients with good prognosis and long life expectancy.


Cardiotoxicity Breast cancer Anthracycline Radiotherapy Old 



Adjusted hazard ratio


Coronary artery disease


Confidence interval




Diabetes mellitus


Hazard ratio


Heart failure




International Classification of Diseases, Ninth Revision, Clinical Modification


Inverse probability of treatment weighting


National Health Insurance Research Database




Standard deviation


Transient ischemic attack

Risiko der Kardiotoxizität induziert durch adjuvante anthrazyklinbasierte Chemotherapie und Strahlentherapie bei jungen und alten asiatischen Frauen mit Brustkrebs



Das Risiko einer Kardiotoxizität durch adjuvante anthrazyklinbasierte Chemotherapie (CT) und Strahlentherapie (RT) muss noch in einer groß angelegten randomisierten kontrollierten Studie mit einer angemessenen Stichprobe von jungen und alten Frauen mit Brustkrebs untersucht werden.

Patienten und Methoden

Um das Auftreten von schweren Herzerkrankungen (Herzinsuffizienz und koronare Herzkrankheit) bei Patientinnen mit Brustkrebs zu vergleichen, wurden 3489 Frauen, bei denen eine chirurgische Resektion des Brusttumors durchgeführt worden war, retrospektiv aus der Taiwan National Health Insurance Research Database ausgewählt. Die Patienten wurden basierend auf ihren Behandlungsmodalitäten in die folgenden Gruppen eingeteilt: Gruppe 1 (n = 1113), keine Behandlung; Gruppe 2 (n = 646), nur adjuvante RT; Gruppe 3 (n = 705), nur adjuvante anthrazyklinbasierte CT; und Gruppe 4 (n = 1025), kombinierte adjuvante RT und anthrazyklinbasierte CT.


Das durchschnittliche Patientenalter betrug 50,35 Jahre. Nachfolgende Koronararterienerkrankung und Herzinsuffizienz wurden bei 244 (7,0 %) bzw. 206 (5,9 %) Patienten festgestellt. Alle 3 adjuvanten Therapien waren signifikante unabhängige prognostische Faktoren für schwere, das Herz betreffende Zwischenfälle (bereinigtes Hazard Ratio [95%-Konfidenzintervall]: 1,47 [1,24–1,73]; 1,48 [1,25–1,75] und 1,92 [1,65–2,23] in den Gruppen 2, 3 bzw. 4). Bei Patienten im Alter von ≥50 Jahren mit Brustkrebs, die sich einer Operation unterziehen mussten, betrugen die logarithmischen p-Werte der Gruppen 2 und 3 nach Anpassung 0,537 bzw. 0,001.


Adjuvante RT kann die Kardiotoxizität bei Patientinnen mit Brustkrebs erhöhen, insbesondere wenn sie in Kombination mit anthrazyklinbasierter CT angewendet wird. Daher sollte sie mit optimalen herzschonenden Techniken angeboten werden, insbesondere bei jüngeren Patienten mit guter Prognose und langer Lebenserwartung.


Kardiotoxizität Brustkrebs Anthrazyklin Strahlentherapie Alt 



We would like to thank Taipei Medical University for funding (108-wf-swf-09).

Author Contributions

Conception and Design: Chih-Hsin Lee, Jun-Fu Zhang and Szu-Yuan Wu; Collection and Assembly of Data: J Chih-Hsin Lee, Jun-Fu Zhang, Kevin Sheng-Po Yuan, Alexander T.H. Wu and Szu-Yuan Wu; Data Analysis and Interpretation: Chih-Hsin Lee, Jun-Fu Zhang and Szu-Yuan Wu; Administrative Support: Szu-Yuan Wu; Manuscript Writing: All authors; Final Approval of Manuscript: All authors


Taipei Medical University and Wan Fang Hospital (108-wf-swf-09)

Compliance with ethical guidelines

Conflict of interest

C.-H. Lee, J.-F. Zhang, K.S.-P. Yuan, A.T.H. Wu and S.-Y. Wu declare that they have no competing interests.

Ethical standards

Our protocols were reviewed and approved by the Institutional Review Board of Taipei Medical University (TMU-JIRB No. 201402018).

Supplementary material

66_2019_1428_MOESM1_ESM.docx (23 kb)
Table S1. Multivariate Cox regression analysis in Asian women with breast cancer who underwent surgery and received different adjuvant treatments (outcome of interest: coronary artery disease).
66_2019_1428_MOESM2_ESM.docx (23 kb)
Table S2. Multivariate Cox regression analysis in Asian women with breast cancer who underwent surgery and received different adjuvant treatments (outcome of interest: heart failure).
66_2019_1428_MOESM3_ESM.docx (23 kb)
Table S3. Multivariate Cox regression analysis in Asian women with breast cancer who underwent surgery and received different adjuvant treatments (interaction analysis for age and adjuvant therapies).
66_2019_1428_MOESM4_ESM.docx (22 kb)
Table S4. Multivariate Cox regression analysis in old (age ≥50 years) Asian women with breast cancer who underwent surgery and received different adjuvant treatments (interaction analysis for radiotherapy and anthracycline-based chemotherapy).
66_2019_1428_MOESM5_ESM.docx (22 kb)
Table S5. Multivariate Cox regression analysis in young (age <50 years) Asian women with breast cancer who underwent surgery and received different adjuvant treatments (interaction analysis for radiotherapy and anthracycline-based chemotherapy).
66_2019_1428_MOESM6_ESM.docx (23 kb)
Table S6. Competing risk analysis by using the cause-specific proportional hazard model in Asian women with breast cancer who underwent surgery and received different adjuvant treatments (endpoint of interest: death).
66_2019_1428_MOESM7_ESM.docx (22 kb)
Table S7. Multivariate Cox regression in 3073 surviving Asian women with breast cancer who underwent surgery and received different adjuvant treatments for risk factors of major cardiac events.
66_2019_1428_MOESM8_ESM.docx (22 kb)
Table S8. Multivariate Cox regression analysis in Asian women with breast cancer who underwent surgery and received different adjuvant treatments (outcome of interest: major cardiac events)
66_2019_1428_MOESM9_ESM.docx (80 kb)
Figure S1. Estimates of cumulative incidence of major cardiac events in Asian women with breast cancer who underwent surgery, as obtained using the inverse probability of treatment weighting-adjusted Kaplan–Meier method and stratified by total dose of radiotherapy.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Chih-Hsin Lee
    • 1
    • 3
    • 7
  • Jun-Fu Zhang
    • 1
  • Kevin Sheng-Po Yuan
    • 4
  • Alexander T. H. Wu
    • 5
  • Szu-Yuan Wu
    • 2
    • 3
    • 6
    • 7
    Email author
  1. 1.Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang HospitalTaipei Medical UniversityTaipeiTaiwan
  2. 2.Institute of Clinical Science, Zhongshan HospitalFudan UniversityShanghaiChina
  3. 3.Department of Internal Medicine, School of Medicine, College of MedicineTaipei Medical UniversityTaipeiTaiwan
  4. 4.Department of Otorhinolaryngology, Wan Fang HospitalTaipei Medical UniversityTaipeiTaiwan
  5. 5.Ph.D. Program for Translational MedicineTaipei Medical UniversityTaipeiTaiwan
  6. 6.Department of Radiation Oncology, Wan Fang Medical CenterTaipei Medical UniversityTaipeiTaiwan
  7. 7.Epidemiology and Bioinformatics Center, Wan fang HospitalTaipei Medical UniversityTaipeiTaiwan

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