Circulating apoptotic proteins are increased in long-term disease-free breast cancer survivors.
Circulating apoptotic proteins are increased in patients with heart failure. We evaluated whether circulating soluble (s) apoptosis-related proteins and inflammation markers are increased in long-term disease free breast cancer survivors and associated with cardiotoxicity, and if subgroups could be identified based on the applied treatments. Circulating tumour necrosis factor (TNF) alpha, sTNF-receptor (sTNF-R) 1 and 2, sFas, sFas ligand, sTNF-related apoptosis inducing ligand (sTRAIL) and serum HER2 were measured with immunoassay. High-sensitivity C-reactive protein (HS-CRP), fibrinogen, plasma B-type and N-terminal atrial natriuretic peptide (NT-ANP and BNP) were also determined. Thirty-four patients with median 6.0 years follow-up and 12 healthy age-matched women were enrolled. Chemotherapy, consisting of five cycles fluorouracil, epirubicin (90 mg/m(2)), cyclophosphamide (FEC) (n=14) or four cycles FEC followed by myeloablation with high-dose carboplatin, cyclophosphamide, thiotepa (n=20), preceded irradiation and tamoxifen. Circulating apoptosis markers were higher in patients than in controls. No associations with cardiac dysfunction were observed. sFas ligand and sTRAIL were higher in the high-dose than in the standard-dose group. In conclusion, we observed increased circulating apoptotic protein levels in long-term disease-free breast cancer survivors, treated with adjuvant chemoradiotherapy, particularly after myeloablative chemotherapy. The potential relation with late cardiotoxicity of antineoplastic therapy deserves further study.
Perik
Patrick J
PJ
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Van der Graaf
Winette T A
WT
De Vries
Elisabeth G E
EG
Boomsma
Frans
F
Messerschmidt
Juergen
J
Van Veldhuisen
Dirk J
DJ
Sleijfer
Dirk T
DT
Gietema
Jourik A
JA
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood* / Q000150:complications / Q000628:therapy*; D002097:C-Reactive Protein / Q000032:analysis; D003430:Cross-Sectional Studies; D018572:Disease-Free Survival; D005260:Female; D006333:Heart Failure / Q000209:etiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011878:Radiotherapy / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood; D053221:TNF-Related Apoptosis-Inducing Ligand; D013629:Tamoxifen / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019014:fas Receptor / Q000097:blood
D051017:Apoptosis Regulatory Proteins; D009320:Atrial Natriuretic Factor; D002097:C-Reactive Protein; D008562:Membrane Glycoproteins; D020097:Natriuretic Peptide, Brain; D018719:Erb-b2 Receptor Tyrosine Kinases; D053221:TNF-Related Apoptosis-Inducing Ligand; D013629:Tamoxifen; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C505653:TNFSF10 protein, human