Abstract | BACKGROUND: Chemo- and radiotherapy for breast cancer (BC) can lead to cardiotoxicity even years after the initial treatment. The pathophysiology behind these late cardiac effects is poorly understood. Therefore, we studied a large panel of biomarkers from different pathophysiological domains in long-term BC survivors, and compared these to matched controls. METHODS AND RESULTS: In total 91 biomarkers were measured in 688 subjects: 342 BC survivors stratified either to treatment with chemotherapy ± radiotherapy (n = 170) or radiotherapy alone (n = 172) and matched controls. Mean age was 59 ± 9 years and 65 ± 8 years for women treated with chemotherapy ± radiotherapy and radiotherapy alone, respectively, with a mean time since treatment of 11 ± 5.5 years. No biomarkers were differentially expressed in survivors treated with radiotherapy alone vs. controls (P for all >0.1). In sharp contrast, a total of 19 biomarkers were elevated, relative to controls, in BC survivors treated with chemotherapy ± radiotherapy after correction for multiple comparisons (P <0.05 for all). Network analysis revealed upregulation of pathways relating to collagen degradation and activation of matrix metalloproteinases. Furthermore, several inflammatory biomarkers including growth differentiation factor 15, monocyte chemoattractant protein 1, chemokine (C-X-C motif) ligand 16, tumour necrosis factor super family member 13b and proprotein convertase subtilisin/kexin type 9, elevated in survivors treated with chemotherapy, showed an independent association with lower left ventricular ejection fraction. CONCLUSION:
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Authors | Jasper Tromp, Liselotte M Boerman, Iziah E Sama, Saskia W M C Maass, John H Maduro, Yoran M Hummel, Marjolein Y Berger, Geertruida H de Bock, Jourik A Gietema, Annette J Berendsen, Peter van der Meer |
Journal | European journal of heart failure
(Eur J Heart Fail)
Vol. 22
Issue 7
Pg. 1239-1246
(07 2020)
ISSN: 1879-0844 [Electronic] England |
PMID | 32078215
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. |
Chemical References |
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Topics |
- Aged
- Biomarkers
- Breast Neoplasms
(drug therapy)
- Female
- Heart Failure
- Humans
- Middle Aged
- Stroke Volume
- Survivors
- Ventricular Function, Left
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