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.
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Patrick J
PJ
Perik
Winette T A
WT
Van der Graaf
Elisabeth G E
EG
De Vries
Frans
F
Boomsma
Juergen
J
Messerschmidt
Dirk J
DJ
Van Veldhuisen
Dirk T
DT
Sleijfer
Jourik A
JA
Gietema
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