title: Comparison of the long term cardiac effects associated with 9 and 52 weeks of trastuzumab in HER2-positive early breast cancer.
abstract: OBJECTIVE
  Trastuzumab induced cardiotoxicity (TIC) was defined as the most serious side effect. Long term cardiac effects of trastuzumab are still not known, thus we aimed to compare the long term cardiac effects of adjuvant trastuzumab therapies of HER2-positive breast cancer according to the treatment duration.
  
  
  METHODS
  Patients who completed adjuvant trastuzumab treatment at least 6 months before for the adjuvant setting in HER2-positive breast cancer were included in the study. A total of 164 patients were included in this study: 108 and 56 patients were treated with 9 weeks and 52 weeks of trastuzumab, respectively. The main limitation of our study is that due to the cross-sectional evaluation of cardiac biomarkers we cannot predict the status of baseline cardiac biomarkers of this population.
  
  
  RESULTS
  The median follow-up of the study was 32 (10-95) months. The accompanying chronic diseases were similar in both groups. Baseline left ventricular ejection fraction (LVEF) was 65.5 ± 3.4% vs 67.1 ± 4.5% in the 9 weeks and 52 weeks trastuzumab treatment groups, respectively (p = 0.13). Symptomatic heart failure was not observed during trastuzumab treatment in either group. Trastuzumab induced cardiotoxicity (TIC) was observed in 2 (1.9%) and 17 (30.3%) patients in the 9 and 52 weeks trastuzumab treatment groups, respectively (p < 0.001). After a median 24 months of follow-up from the last dose of trastuzumab, mean LVEF values were similar between the two treatment arms (p = 0.29). In the subgroup analyses, mean LVEF values were significantly lower in patients who developed TIC compared to those who did not develop TIC (61.9 ± 3.6% vs 64.4 ± 2.6%, p = 0.04). Average mean LVEF loss from baseline was significantly higher in patients who developed TIC compared to those who did not develop TIC (10.0 ± 6.0% vs 1.5 ± 6.2%, p < 0.001). Cardiac biomarkers were similar in both treatment groups. In the subgroup analyses serum High-sensitivity C-reactive protein (hs-CRP) and prohormone brain natriuretic peptide (pro-BNP) levels were significantly higher in patients who developed TIC compared to those who did not develop TIC.
  
  
  CONCLUSIONS
  TIC was observed to be significantly higher in the 52 weeks trastuzumab group. At the end of 32 months of follow-up mean LVEF values and cardiac biomarkers were similar between the two treatment groups. In the subgroup analyses, significant LVEF loss and higher cardiac biomarkers which show cardiac damage in patients who developed TIC can be permanent in some of the patients and long term cardiac damage may be underestimated.
authors.affiliation: Yıldırım Beyazıt University, Department of Medical Oncology , Ankara , Turkey.
authors.forename: Mehmet Ali Nahit
authors.initials: MA
authors.lastname: Şendur
authors.forename: Sercan
authors.initials: S
authors.lastname: Aksoy
authors.forename: Hikmet
authors.initials: H
authors.lastname: Yorgun
authors.forename: Nuriye
authors.initials: N
authors.lastname: Ozdemir
authors.forename: Fatma Meric
authors.initials: FM
authors.lastname: Yilmaz
authors.forename: Ozan
authors.initials: O
authors.lastname: Yazıcı
authors.forename: Cevdet
authors.initials: C
authors.lastname: Zungun
authors.forename: Kudret
authors.initials: K
authors.lastname: Aytemir
authors.forename: Nurullah
authors.initials: N
authors.lastname: Zengin
authors.forename: Kadri
authors.initials: K
authors.lastname: Altundag
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D002097:C-Reactive Protein / Q000032:analysis; D066126:Cardiotoxicity; D003430:Cross-Sectional Studies; D055088:Early Detection of Cancer; D061345:Early Medical Intervention; D005260:Female; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis; D006801:Humans; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D013318:Stroke Volume; D013995:Time; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D002097:C-Reactive Protein; D020097:Natriuretic Peptide, Brain; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C109794:pro-brain natriuretic peptide (1-76); C508053:ERBB2 protein, human
keywords: Breast cancer; HER2; Trastuzumab; Trastuzumab induced cardiotoxicity