Clinical and genetic risk factors for epirubicin-induced cardiac toxicity in early breast cancer patients

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• 作者：Christof Vulsteke ; Alena M. Pfeil ; Charlotte Maggen…
• 关键词：Anthracycline ; induced cardiotoxicity ; Genetic variability ; Early breast cancer ; Left ventricular ejection fraction
• 刊名：Breast Cancer Research and Treatment
• 出版年：2015
• 出版时间：July 2015
• 年：2015
• 卷：152
• 期：1
• 页码：67-76
• 全文大小：384 KB
• 参考文献：1.Roché H, Fumoleau P, Spielmann M, Canon JL, Delozier T, Serin D, Symann M, Kerbrat P, Soulié P, Eichler F, Viens P, Monnier A, Vindevoghel A, Campone M, Goudier MJ, Bonneterre J, Ferrero JM, Martin AL, Genève J, Asselain B (2006) Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 trial. J Clin Oncol 24(36):5664-671PubMed View Article
  2.Kremer LC, van der Pal HJ, Offringa M, van Dalen EC, Vo?te PA (2002) frequency and risk factors of subclinical cardiotoxicity after anthracycline therapy in children: a systematic review. Ann Oncol 13(6):819-29PubMed View Article
  3.Shan K, Lincoff AM, Young JB (1996) Anthracycline-induced cardiotoxicity. Ann Intern Med 125(1):47-8PubMed View Article
  4.Barry E, Alvarez JA, Scully RE, Miller TL, Lipshultz SE (2007) Anthracycline-induced cardiotoxicity: course, pathophysiology, prevention and management. Expert Opin Pharmacother 8(8):1039-058PubMed View Article
  5.Roca-Alonso L, Pellegrino L, Castellano L, Strebbin J (2012) Breast cancer treatment and adverse cardiac events: what are the molecular mechanisms? Cardiology 122(4):253-59PubMed View Article
  6.Hudson MM, Rai SN, Nunez C, Merchant TE, Marina NM, Zalamea N, Cox C, Phipps S, Pompeu R, Rosenthal D (2007) Noninvasive evaluation of late anthracycline cardiac toxicity in childhood cancer survivors. J Clin Oncol 25(24):3635-643PubMed View Article
  7.Wildiers H, Jurcut R, Ganame J, Herbots L, Neven P, De Backer J, Denys H, Cocquyt V, Rademakers F, Voigt JU, Paridaens R (2008) A Pilot study to investigate the feasibility and cardiac effects of pegylated liposomal doxorubicin (PL-DOX) as adjuvant therapy in medically fit elderly breast cancer patients. Crit Rev Hematol 67(2):133-38View Article
  8.Jurcut R, Wildiers H, Ganame J, D’hooge J, De Backer J, Denys H, Paridaens R, Rademakers F, Voigt JU (2008) Strain rate imaging detects early cardiac effects of pegylated liposomal doxorubicin as adjuvant therapy in elderly patients with breast cancer. J Am Soc Echocardiogr 21(12):1283-289PubMed View Article
  9.Vulsteke C, Lambrechts D, Dieudonné A, Hatse S, Brouwers B, van Brussel T, Neven P, Belmans A, Sch?ffski P, Paridaens R, Wildiers H (2013) Genetic variability in the multidrug resistance associated protein-1 (ABCC1/MRP1) predicts hematological toxicity in breast cancer patients receiving (neo-)adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide (FEC). Ann Oncol 24:1513-525PubMed View Article
  10.Semsei AF, Erdelyi DJ, Ungvari I, Csagoly E, Hegyi MZ, Kiszel PS, Lautner-Csorba O, Szabolcs J, Masat P, Fekete G, Falus A, Szalai C, Kovacs GT (2012) ABCC1 polymorphisms in anthracycline-induced cardiotoxicity in childhood acute lymphoblatic leukaemia. Cell Biol Int 36(1):79-6PubMed View Article
  11.Wojnowski L, Kulle B, Schirmer M, Schlüter G, Schmidt A, Rosenberger A, Vonhof S, Bickeb?ller H, Toliat MR, Suk EK, Tzvetkov M, Kruger A, Seifert S, Kloess M, Hahn H, Loeffler M, Nürnberg P, Pfreundschuh M, Trümper L, Brockm?ller J, Hasenfuss G (2005) NAD(P)H oxidase and multidrug resistance protein genetic polymorphisms are associated with doxorubicin-induced cardiotoxicity. Circulation 112(24):3754-762PubMed View Article
  12.Visscher H, Ross CJ, Rassekh SR, Barhdadi A, Dubé MP, AL-Saloos H, Sandor GS, Caron HN, van Dalen EC, Kremer LC, van der Pal HJ, Brown AM, Rogers PC, Phillips MS, Rieder MJ, Carleton BC, Hayden MR, Canadian Pharmacogenomics Network for Drug Safety Consortium (2012) Pharmacogenomic prediction of anthracycline-induced cardiotoxicity in children. J Clin Oncol 30(13):1422-428PubMed View Article
  13.Visscher H, Ross CJ, Rassekh SR, Sandro GS, Caron HN, van Dalen EC, Kremer LC, van der Pal HJ, Rogers PC, Rieder MJ, Carleton BC, Hayden MR, CPNDS Consortium (2013) Validation of variants in SLC28A3 and UGT1A6 as genetic markers predictive of anthracycline-induced cardiotoxicity in children. Pediatr Blood Cancer 60(8):1375-381PubMed View Article
  14.Rajic V, Aplenc R, Debeljak M, Prestor VV, Karas-Kuzelicki N, Mlinaric-Rascan I, Jazbec J (2009) Influence of the polymorphism in candidate genes on late cardiac damage in patients treated due to leukemia in childhood. Leuk Lymphoma 50(10):1693-698PubMed View Article
  15.Cascales A, Pastor-Quirante F, Sanchez-Vega B, Luengo-Gil G, Corral J, Ortuno-Pacheco G, Vicente V, de la Pena FA (2013) Association of anthracycline-related cardiac histological lesions with NADPH oxidase functional polymorphisms. Oncologist. 18(4):446-53PubMed Central PubMed View Article
  16.Blanco JG, Sun CL, Landier W, Chen L, Esparza-Duran D, Leisenring W, Mays A, Friedman DL, Ginsberg JP, Hudson MM, Neglia JP, Oeffinger KC, Ritchey AK, Villaluna D, Relling MV, Bhatia S (2012) Anthracycline-related cardiomyopathy after childhood cancer: role of polymorphisms in carbonyl reductase genes—a report from the Children’s Oncology Group. J Clin Oncol 30(13):141
• 作者单位：Christof Vulsteke (1)
  Alena M. Pfeil (2)
  Charlotte Maggen (3)
  Matthias Schwenkglenks (2)
  Ruth Pettengell (4)
  Thomas D. Szucs (2)
  Diether Lambrechts (5) (6)
  Anne-Sophie Dieudonné (3)
  Sigrid Hatse (7)
  Patrick Neven (3)
  Robert Paridaens (7)
  Hans Wildiers (7)
  
  1. Integrated Cancer Center Ghent, AZ Maria Middelares, Ghent, Belgium
  2. Institute of Pharmaceutical Medicine (ECPM), University of Basel, Basel, Switzerland
  3. Department of Gynaecology and Obstetrics, University Hospitals Leuven, Louvain, Belgium
  4. Cellular and Molecular Medicine, St. George’s University of London, London, UK
  5. Vesalius Research Center, Vlaams Instituut voor Biotechnologie (VIB), Louvain, Belgium
  6. Laboratory for Translational Genetics, Department of Oncology, KU Leuven, Louvain, Belgium
  7. Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Herestraat 49, 3000, Louvain, Belgium
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7217

文摘

Anthracycline-induced cardiotoxicity (ACT) is a well-known serious adverse drug reaction leading to substantial morbidity. The purpose of this study was to assess ACT occurrence and clinical and genetic risk factors in early breast cancer patients. In 6 genes of interest (ABCC1, ABCC2, CYBA, NCF4, RAC2, SLC28A3), 10 single nucleotide polymorphisms (SNPs) involved in ACT were selected based on a literature search. Eight hundred and seventy-seven patients treated between 2000 and 2010 with 3- cycles of (neo) adjuvant 5-fluorouracil, epirubicin and cyclophosphamide (FEC) were genotyped for these SNPs using Sequenom MassARRAY. Main outcome measures were asymptomatic decrease of left ventricular ejection fraction (LVEF)?>?10?% and cardiac failure grade 3- (CTCAE 4.0). To evaluate the impact of these 10 SNPs as well as clinical factors (age, relative dose intensity of epirubicin, left-sided radiotherapy, occurrence of febrile neutropenia, and planned and received cycles of epirubicin) on decrease of LVEF and cardiac failure, we performed uni- and multivariable logistic regression analysis. Additionally, exploratory analyses including 11 additional SNPs related to the metabolism of anthracyclines were performed. After a median follow-up of 3.62?years (range 0.40-.60), a LVEF decline of?>?10?% occurred in 153 patients (17.5?%) and cardiac failure in 16 patients (1.8?%). In multivariable analysis, six cycles of FEC compared to three cycles received and heterozygous carriers of the rs246221 T-allele in ABCC1 relative to homozygous carriers of the T-allele were significantly associated with LVEF decline of?>?10?% (OR 1.3, 95?% CI 1.1-.4, p?<?0.001 and OR 1.6, 95?% CI 1.1-.3, p?=?0.02). Radiotherapy for left-sided breast cancer was associated with cardiac failure (OR 3.7, 95?% CI 1.2-1.5, p 0.026). The other 9 SNPs and clinical factors tested were not significantly associated. In our exploratory analysis, no other SNPs related to anthracycline metabolism were retained in the multivariate model for prediction of LVEF decline. ACT in breast cancer patients is related to number of received cycles of epirubicin and left-sided radiotherapy. Additional studies should be performed to independently confirm the potential association between rs246221 in ABCC1 and LVEF.