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Trastuzumab cardiotoxicity

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https://www.readbyqxmd.com/read/29305325/modeling-trastuzumab-related-cardiotoxicity-in-vitro-using-human-stem-cell-derived-cardiomyocytes
#1
Yosuke K Kurokawa, Michael R Shang, Rose T Yin, Steven C George
Trastuzumab (Herceptin®), a monoclonal antibody against the ErbB2 (HER2) receptor, has significantly improved clinical outcomes for HER2+ breast cancer patients. However, the drug also has known cardiotoxic side effects through mechanisms that are not fully understood. Here we utilized human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) to model trastuzumab-related cardiotoxicity in vitro. We demonstrate that cardiotoxic effects of ErbB2 inhibition by trastuzumab can be recapitulated only when the cardioprotective effects of ErbB2/4 signaling is observed...
January 2, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29280043/cardiac-biomarkers-for-early-detection-and-prediction-of-trastuzumab-and-or-lapatinib-induced-cardiotoxicity-in-patients-with-her2-positive-early-stage-breast-cancer-a-neoaltto-sub-study-big-1-06
#2
Noam Ponde, Ian Bradbury, Matteo Lambertini, Michael Ewer, Christine Campbell, Helene Ameels, Dimitrios Zardavas, Serena Di Cosimo, José Baselga, Jens Huober, Miguel Izquierdo, Debora Fumagalli, Ivana Bozovic-Spasojevic, Marion Maetens, Nadia Harbeck, Lajos Pusztai, Michael Berghorn, Young-Hyuck Im, Manuel Ruiz Borrego, Dar-Ren Chen, Richard Rodeheffer, Martine Piccart, Thomas Suter, Evandro de Azambuja
BACKGROUND: Biomarkers of cardiac damages, such as troponin T (TnT) and the amino-terminal fragment of brain natriuretic peptide (NT-proBNP), may be useful as early predictors of cardiac dysfunction. The role of these biomarkers in patients receiving lapatinib and/or trastuzumab before anthracyclines is unknown. This study explores TnT and NT-proBNP as predictors of early cardiac toxicity in neoadjuvant breast cancer patients. METHODS: This sub-study of the NEOALTTO trial tested if changes in the levels of TnT and NT-proBNP occurred after 2 weeks of anti-HER2 therapy (lapatinib, trastuzumab or their combination) alone and/or after 18 weeks of anti-HER2 therapy plus weekly paclitaxel...
December 27, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29247589/whole-exome-sequencing-to-identify-genetic-markers-for-trastuzumab-induced-cardiotoxicity
#3
Chihiro Udagawa, Hiromi Nakamura, Hiroshi Ohnishi, Kenji Tamura, Tatsunori Shimoi, Masayuki Yoshida, Teruhiko Yoshida, Yasushi Totoki, Tatsuhiro Shibata, Hitoshi Zembutsu
Although trastuzumab-induced cardiotoxicity is an important determinant to limit the use of this drug, the molecular mechanism of risk for this toxicity is not well understood. To identify genetic variants determining the risk of trastuzumab-induced cardiotoxicity, we performed whole exome sequencing of germline DNA samples from 9 patients with trastuzumab-induced cardiotoxicity, and conducted a case-control association study of 2,258 genetic variants between 9 cases (with trastuzumab-induced cardiotoxicity) and general Japanese population controls registered in Human Genetic Variation Database (HGVD)...
December 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/29231164/lapatinib-plus-capecitabine-in-patients-with-her2-positive-metastatic-breast-cancer-a%C3%A2-systematic-review%C3%A2
#4
Rebecca Madden, Sam Kosari, Gregory M Peterson, Nasser Bagheri, Jackson Thomas
OBJECTIVE: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which accounts for 20 - 25% of cases of breast cancers, is highly aggressive. Due to cardiotoxicity and increasing resistance associated with trastuzumab, the first-line treatment, there is a need for effective second-line therapies in treating HER2-positive breast cancer. In this context, there has been increasing interest in the combination of lapatinib plus capecitabine. The aim of this systematic review was to assess the efficacy of lapatinib plus capecitabine for HER2-positive breast cancer after progression with trastuzumab therapy, in comparison with capecitabine monotherapy and other agents such as vinorelbine and trastuzumab emtansine...
December 12, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29225726/incidence-diagnosis-and-treatment-of-cardiac-toxicity-from-trastuzumab-in-patients-with-breast-cancer
#5
Somaira Nowsheen, Paul V Viscuse, Ciara C O'Sullivan, Nicole P Sandhu, Tufia C Haddad, Anne Blaes, Jennifer Klemp, Lara Nhola, Joerg Herrmann, Kathryn J Ruddy
Purpose of review: Treatment with trastuzumab is a cornerstone of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer treatment, but carries an unfortunate risk of toxicity to the cardiovascular system. Here we review recent findings on trastuzumab-associated cardiotoxicity, focusing on its incidence, diagnosis, and treatment. Recent findings: Screening with multigated acquisition scan (MUGA) or echocardiogram (ECHO) is recommended to assess cardiac function prior to and during trastuzumab therapy...
September 2017: Current Breast Cancer Reports
https://www.readbyqxmd.com/read/29199719/retrospective-study-of-efficacy-and-safety-of-neoadjuvant-docetaxel-carboplatin-and-trastuzumab-in-her2-positive-locally-advanced-and-oligometastatic-breast-cancer-an-indian-experience
#6
A Tiwari, A Gogia, Svs Deo, N K Shukla, S Mathur, D N Sharma
BACKGROUND: The neoadjuvant chemotherapy in HER2-positive breast cancer consists of a chemotherapy backbone and HER2-directed therapy. The increase in cardiotoxicity by the use of trastuzumab with an anthracycline-based regimen has led to the use of nonanthracycline-based alternative regimens. The docetaxel, carboplatin, and trastuzumab (TCH) are one such regimen. The efficacy and toxicity of this regimen have not been widely studied in Indian patients. AIMS: This retrospective study aims to evaluate the efficacy and toxicity of neoadjuvant TCH regimen in locally advanced and oligometastatic HER2-positive breast cancer in Indian patients...
January 2017: Indian Journal of Cancer
https://www.readbyqxmd.com/read/29189161/toxicology-of-trastuzumab-an-insight-into-mechanisms-of-cardiotoxicity
#7
Jie An, M Saeed Sheikh
Trastuzumab is a humanized monoclonal antibody that is approved for the treatment of breast and gastric malignancies. Although it has shown promise as a biotherapeutic, its cardiotoxicity remains a major concern. Genotoxic anticancer anthracyclines such as doxorubicin and epirubicin are also known for their cardiotoxic effects. However, trastuzumab and anthracyclines are suggested to mediate cardiotoxicity via different pathways. The available lines of evidence suggest that trastuzumab can exacerbate the cardiotoxic effects of anthracyclines and thus, prior exposure to anthracyclines is a regarded as one of the risk factors for trastuzumab-induced cardiotoxcity...
November 29, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29164397/factors-for-time-to-trastuzumab-induced-cardiotoxicity-in-breast-cancer-patients
#8
Mi Hyung Lee, Jeong Yee, Young Ju Kim, Jin Young Moon, Joo Hee Kim, Sandy Jeong Rhie, Hye Sun Gwak
Trastuzumab is a drug used for the treatment of metastatic breast cancer patients. Due to blockage of the human epidermal growth factor receptor 2 signaling in cardiac myocytes, cardiotoxicity has been observed. There are many studies that investigated risk factors for trastuzumab-induced cardiotoxicity, but no study has been published for factors on the time to cardiotoxicity. This study aimed to investigate the factors for the time to occur trastuzumab-induced cardiotoxicity. From January 2014 to December 2015, a retrospective study was performed with breast cancer patients who were treated with trastuzumab...
November 21, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29115937/trastuzumab-resumption-after-extremely-severe-cardiotoxicity-in-metastatic-breast-cancer-patient-a-case-report
#9
Santino Minichillo, Ilaria Gallelli, Elena Barbieri, Marta Cubelli, Daniela Rubino, Sara Quercia, Massimo Dall'Olio, Claudio Rapezzi, Claudio Zamagni
BACKGROUND: Trastuzumab-related cardiotoxicity has been reported in patients receiving trastuzumab concurrently with other agents, especially with anthracyclines. Cardiac function damage is generally rare, precox and mild with trastuzumab alone. CASE PRESENTATION: We report the case of a 49 year-old woman affected by metastatic breast cancer who developed trastuzumab-related cardiogenic shock due to pump failure (with LVEF of about 15%) after three months of treatment...
November 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29108307/association-between-obesity-and-trastuzumab-related-cardiac-toxicity-in-elderly-patients-with-breast-cancer
#10
Hai-Yan Wang, Bei-Bei Yin, Dan-Yan Jia, Ying-Long Hou
Purpose: Trastuzumab can improve the prognosis for patients with breast cancer, but its related cardiac toxicity is concerning. This study aimed to identify the risk factors associated with trastuzumab-related cardiac toxicity in elderly patients with HER2-positive breast cancer. Patients and methods: A total of 133 elderly (≥ 65 years) patients who were diagnosed with breast cancer between June 1, 2007, and January 31, 2016, and received trastuzumab treatment were retrospectively reviewed...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977908/cardiotoxicity-of-trastuzumab-in-patients-with-her2-positive-gastric-cancer
#11
Ji Soo Park, Jong-Chan Youn, Chi Young Shim, Geu-Ru Hong, Choong-Kun Lee, Jee Hyung Kim, Hyung Soon Park, Su Jin Heo, Seung Hoon Beom, Hyo Song Kim, Sun Young Rha, Hyun Cheol Chung, Seok-Min Kang, Minkyu Jung
Trastuzumab-induced cardiotoxicity (TIC) is the primary adverse event that limits the use of trastuzumab in HER2-positive breast cancer patients. However, the incidence and risk factors of TIC in HER2-positive gastric cancer are not known. Therefore, we evaluated the incidence and predictive factors of TIC in gastric cancer patients treated with trastuzumab in clinical practice. We reviewed cardiac dysfunction in HER2-positive gastric cancer patients between December 2005 and April 2015 in a prospectively-collected database that included prospective clinical trials at Yonsei Cancer Center, Republic of Korea...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28936442/cardiotoxicity-of-cancer-chemotherapy-identification-prevention-and-treatment
#12
REVIEW
Diwakar Jain, Tauseef Ahmad, Mitchel Cairo, Wilbert Aronow
Cardiotoxicity is an important complication of several cancer therapeutic agents. Several well established and newer anticancer therapies such as anthracyclines, trastuzumab and other HER2 receptor blockers, antimetabolites, alkylating agents, tyrosine kinase inhibitors (TKIs), angiogenesis inhibitors, and checkpoint inhibitors are associated with significant cardiotoxicity. Cardiovascular imaging employing radionuclide imaging, echocardiography and magnetic resonance imaging are helpful in early detection and prevention of overt heart failure secondary to cardiotoxicity of cancer therapy...
September 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28863313/duration-of-adjuvant-trastuzumab-in-her2-positive-breast-cancer-overall-and-disease-free-survival-results-from-meta-analyses-of-randomized-controlled-trials
#13
REVIEW
Bishal Gyawali, Saroj Niraula
BACKGROUND: One year of trastuzumab, chosen empirically, improves survival of women with early-stage, HER2-positive breast cancer but also adds substantially to cost, toxicity, and inconvenience. Longer treatment does not improve outcomes, but potentiates toxicities. METHODS: Medline, Embase, and major conference proceedings were searched systematically in June 2017 to identify Randomized Controlled Trials (RCTs) comparing one year versus shorter durations of trastuzumab in adjuvant treatment of breast cancer...
November 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28822666/reliability-of-left-ventricular-ejection-fraction-from-three-dimensional-echocardiography-for-cardiotoxicity-onset-detection-in-patients-with-breast-cancer
#14
Cinzia Lorenzini, Claudio Lamberti, Michele Aquilina, Andrea Rocca, Pietro Cortesi, Cristiana Corsi
BACKGROUND: Cardiotoxicity is a well-known adverse effect of various chemotherapeutic agents that can be monitored by echocardiography. A decrease in left ventricular ejection fraction (LVEF) triggers consideration for therapy modification or interruption. The aim of this study was to evaluate how variability in LVEF estimates computed using three-dimensional echocardiography could influence cardiotoxicity onset detection. METHODS: One hundred eighty one patients with breast cancer treated with anthracycline and trastuzumab were analyzed...
August 16, 2017: Journal of the American Society of Echocardiography
https://www.readbyqxmd.com/read/28781309/congestive-heart-failure-during-osimertinib-treatment-for-epidermal-growth-factor-receptor-egfr-mutant-non-small-cell-lung-cancer-nsclc
#15
Hiromi Watanabe, Eiki Ichihara, Hirohisa Kano, Kiichiro Ninomiya, Mitsune Tanimoto, Katsuyuki Kiura
We herein report a case of congestive heart failure which developed during osimertinib treatment. A 78-year-old woman presented with mild exertional dyspnea three weeks after starting osimertinib for the treatment of epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer. She was diagnosed with congestive heart failure caused by the osimertinib. In contrast to trastuzumab, a human epidermal growth factor receptor 2 (HER2) monoclonal antibody that often causes cardiac dysfunction, the causal relationship between osimertinib and cardiotoxicity has so far received little attention and thus remains unclear...
August 15, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28763429/genome-wide-association-study-of-cardiotoxicity-in-the-ncctg-n9831-alliance-adjuvant-trastuzumab-trial
#16
Daniel J Serie, Julia E Crook, Brian M Necela, Travis J Dockter, Xue Wang, Yan W Asmann, DeLisa Fairweather, Katelyn A Bruno, Gerardo Colon-Otero, Edith A Perez, E Aubrey Thompson, Nadine Norton
OBJECTIVES: The major clinical side effect of the ERBB2-targeted breast cancer therapy, trastuzumab, is a decline in the left ventricular ejection fraction (LVEF). Improved markers are needed to better identify patients susceptible to cardiotoxicity. METHODS: The NCCTG N9831 trial compared adjuvant doxorubicin and cyclophosphamide followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or concurrent paclitaxel and trastuzumab (arm C) in patients with HER2-positive breast cancer...
October 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28759384/cardiotoxic-effects-of-anthracycline-based-therapy-what-is-the-evidence-and-what-are-the-potential-harms
#17
REVIEW
Bennett E Levis, Phillip F Binkley, Charles L Shapiro
Despite the known cardiotoxic effects of doxorubicin and other anthracyclines, no evidence-based guidelines exist for the surveillance and prevention of chemotherapy-induced cardiotoxicity in adult survivors of breast cancer who have had limited previous doses of anthracyclines (ie, total cumulative dose 240 mg/m2), or limited-dose anthracyclines followed by trastuzumab-based regimens. Nonetheless, some national and international cardio-oncology and cardiac-imaging organisations recommend increased cardiac surveillance during or after treatment, measurement of cardiac biomarkers and other surrogate endpoints, and in some cases initiation of cardioprotective drug therapy in asymptomatic women...
August 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28736636/biological-agents-in-gastrointestinal-cancers-adverse-effects-and-their-management
#18
REVIEW
Nivedita Arora, Arjun Gupta, Preet Paul Singh
Biological therapy comprises agents that by virtue of their unique mechanisms of action, are able to specifically incite a response against or target malignant cells. They differ from conventional chemotherapy with regard to mechanisms of action, indications and side effect profile. Biologic agents have revolutionized therapy for a number of malignancies. In the setting of gastrointestinal (GI) malignancies, agents targeting vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (Her2/Neu) and epidermal growth factor receptor (EGFR) have proven to be invaluable additions to chemotherapy...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28735727/investigation-of-the-role-of-dna-methylation-in-the-expression-of-erbb2-in-human-myocardium
#19
Adolfo Quiñones-Lombraña, Rachael Hageman Blair, Javier G Blanco
The ERBB2 gene encodes a transmembrane tyrosine kinase receptor that belongs to the epidermal growth factor receptor (EGFR) family. ERBB2 plays a pivotal role during heart development and is essential for normal cardiac function, particularly during episodes of cardiac stress. The monoclonal antibody drug trastuzumab is used for the therapy of breast cancers that overexpress ERBB2. The clinical use of trastuzumab is limited by the development of cardiotoxicity in some patients. Inter-individual differences in the expression of ERBB2 in cardiac tissue may impact the risk of cardiotoxicity...
September 10, 2017: Gene
https://www.readbyqxmd.com/read/28710537/cardiac-safety-of-non-anthracycline-trastuzumab-based-therapy-for-her2-positive-breast-cancer
#20
Anthony F Yu, Roy B Mukku, Shivani Verma, Jennifer E Liu, Kevin C Oeffinger, Richard M Steingart, Clifford A Hudis, Chau T Dang
PURPOSE: Trastuzumab improves overall survival for women with HER2-positive breast cancer but is associated with cardiotoxicity, especially when administered after anthracyclines. Use of non-anthracycline trastuzumab-based regimens is rising, particularly for patients with low-risk disease or with multiple cardiovascular risk factors. We performed a single-center retrospective cohort study to assess the cardiac safety of trastuzumab without anthracyclines outside of a clinical trial setting...
November 2017: Breast Cancer Research and Treatment
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