Influence of Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in early-stage HER2 positive breast cancer

Abstract Trastuzumab has improved the prognosis of HER2 positive breast cancer, but cardiotoxicity remains a concern. We aimed to identify risk factors for trastuzumab-induced cardiotoxicity, with an emphasis on the HER2 Ile655Val single nucleotide polymorphism. This single-center case–control study...

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Autores principales:	Ljubica Vazdar, Ivo Darko Gabrić, Ivan Kruljac, Hrvoje Pintarić, Robert Šeparović, Lora Stanka Kirigin Biloš, Mirjana Pavlović, Ana Tečić Vuger, Mario Štefanović
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b0792d63096946bf96cbd11450c1c581
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spelling	oai:doaj.org-article:b0792d63096946bf96cbd11450c1c5812021-12-02T15:33:12ZInfluence of Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in early-stage HER2 positive breast cancer10.1038/s41598-021-93634-62045-2322https://doaj.org/article/b0792d63096946bf96cbd11450c1c5812021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93634-6https://doaj.org/toc/2045-2322Abstract Trastuzumab has improved the prognosis of HER2 positive breast cancer, but cardiotoxicity remains a concern. We aimed to identify risk factors for trastuzumab-induced cardiotoxicity, with an emphasis on the HER2 Ile655Val single nucleotide polymorphism. This single-center case–control study included 1056 patients with early-stage HER2 positive breast cancer that received adjuvant trastuzumab. Cardiotoxicity was defined as a decline in left ventricular ejection fraction (LVEF) > 15% in patients without previous cardiomyopathy, or > 10% in patients with baseline LVEF of < 50%. Patient characteristics and cardiac parameters were compared in 78 (7.38%) cases and 99 randomly assigned controls, and the polymorphism was genotyped using real-time polymerase chain reaction. Cardiotoxicity was independently associated with advanced age (P = 0.024), lower body mass index (P = 0.023), left breast involvement (P = 0.001), N3 status (P = 0.004), diabetes (P = 0.016), and a family history of coronary artery disease (P = 0.019). Genotype distribution was as follows: A/A (Ile/Ile) was found in 111 (62.7%) patients, A/G (Ile/Val) in 60 (33.9%) patients, and G/G (Val/Val) in 6 (3.4%) patients. The genotype was not associated with cardiotoxicity or the severity of heart failure, reversibility, and recovery time. We found no association between the HER2 Ile655Val polymorphism and trastuzumab-induced cardiotoxicity; therefore, we do not recommend routine cardiotoxicity-risk stratification using this polymorphism.Ljubica VazdarIvo Darko GabrićIvan KruljacHrvoje PintarićRobert ŠeparovićLora Stanka Kirigin BilošMirjana PavlovićAna Tečić VugerMario ŠtefanovićNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ljubica Vazdar Ivo Darko Gabrić Ivan Kruljac Hrvoje Pintarić Robert Šeparović Lora Stanka Kirigin Biloš Mirjana Pavlović Ana Tečić Vuger Mario Štefanović Influence of Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in early-stage HER2 positive breast cancer
description	Abstract Trastuzumab has improved the prognosis of HER2 positive breast cancer, but cardiotoxicity remains a concern. We aimed to identify risk factors for trastuzumab-induced cardiotoxicity, with an emphasis on the HER2 Ile655Val single nucleotide polymorphism. This single-center case–control study included 1056 patients with early-stage HER2 positive breast cancer that received adjuvant trastuzumab. Cardiotoxicity was defined as a decline in left ventricular ejection fraction (LVEF) > 15% in patients without previous cardiomyopathy, or > 10% in patients with baseline LVEF of < 50%. Patient characteristics and cardiac parameters were compared in 78 (7.38%) cases and 99 randomly assigned controls, and the polymorphism was genotyped using real-time polymerase chain reaction. Cardiotoxicity was independently associated with advanced age (P = 0.024), lower body mass index (P = 0.023), left breast involvement (P = 0.001), N3 status (P = 0.004), diabetes (P = 0.016), and a family history of coronary artery disease (P = 0.019). Genotype distribution was as follows: A/A (Ile/Ile) was found in 111 (62.7%) patients, A/G (Ile/Val) in 60 (33.9%) patients, and G/G (Val/Val) in 6 (3.4%) patients. The genotype was not associated with cardiotoxicity or the severity of heart failure, reversibility, and recovery time. We found no association between the HER2 Ile655Val polymorphism and trastuzumab-induced cardiotoxicity; therefore, we do not recommend routine cardiotoxicity-risk stratification using this polymorphism.
format	article
author	Ljubica Vazdar Ivo Darko Gabrić Ivan Kruljac Hrvoje Pintarić Robert Šeparović Lora Stanka Kirigin Biloš Mirjana Pavlović Ana Tečić Vuger Mario Štefanović
author_facet	Ljubica Vazdar Ivo Darko Gabrić Ivan Kruljac Hrvoje Pintarić Robert Šeparović Lora Stanka Kirigin Biloš Mirjana Pavlović Ana Tečić Vuger Mario Štefanović
author_sort	Ljubica Vazdar
title	Influence of Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in early-stage HER2 positive breast cancer
title_short	Influence of Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in early-stage HER2 positive breast cancer
title_full	Influence of Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in early-stage HER2 positive breast cancer
title_fullStr	Influence of Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in early-stage HER2 positive breast cancer
title_full_unstemmed	Influence of Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in early-stage HER2 positive breast cancer
title_sort	influence of ile655val polymorphism on trastuzumab-induced cardiotoxicity in early-stage her2 positive breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b0792d63096946bf96cbd11450c1c581
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Influence of Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in early-stage HER2 positive breast cancer

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