Twenty years of anti-HER2 therapy-associated cardiotoxicity

Pondé, Noam; Lambertini, Matteo; Azambuja, Evandro de

doi:10.1136/esmoopen-2016-000073

Cited by 85 publications

(69 citation statements)

References 127 publications

(136 reference statements)

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“…On the other hand, studies have indicated that obesity might increase the risk of cardiac toxicity in breast cancer patients who received trastuzumab (HER2-targeted monoclonal antibody) therapy [108], [109], [110]. Evidence shows that HER2 plays important physiological roles in the development of the heart and cardiomyocyte survival [111], [112]. Therefore, treatment with trastuzumab could be associated with the deleterious effects of the HER2 blockade (Table 5).…”

Section: Characteristics Of Her2 Expressionmentioning

confidence: 99%

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

Ray

2017

Hormone Molecular Biology and Clinical Investigation

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Abstract:Obesity is associated with the risk of several health disorders including certain cancers. Among obesity-related cancers, postmenopausal breast carcinoma is a well-studied one. Apart from an increase in certain types of lipids in obesity, excess adipose tissue releases many hormone-like cytokines/adipokines, which are usually pro-inflammatory in nature. Leptin is one of such adipokines and significantly linked with the intracellular signaling pathways of other growth factors such as insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2). In general, HER2 is overexpressed in roughly 30% of breast carcinomas; its presence indicates aggressive tumor behavior. Conversely, HER2 has certain effects in normal conditions such as differentiation of preadipocytes, cardiovascular health and vitamin D metabolism. HER2 has no known endogenous ligand, but it may form dimers with other three members of the epidermal growth factor receptor (EGFR) family and can activate downstream signaling pathways. Furthermore, HER2 is intimately connected with several enzymes, e.g. fatty acid synthase (FASN), phosphatidylinositol 3-kinase (PI3K), AKT and mechanistic target of rapamycin (mTOR), all of which play significant regulatory roles in lipogenic pathways or lipid metabolism. In obesity-related carcinogenesis, characteristics like insulin resistance and elevated IGF-1 are commonly observed. Both IGF-1 and leptin can modulate EGFR and HER2 signaling pathways. Although clinical studies have shown mixed results, the behavior of HER2+ tumor cells including HER2 levels can be altered by several factors such as obesity, leptin and fatty acids. A precise knowledge is useful in new therapeutic approaches against HER+ tumors.

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Section: Characteristics Of Her2 Expressionmentioning

confidence: 99%

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

Ray

2017

Hormone Molecular Biology and Clinical Investigation

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“…Transaminase elevations are usually transient and without any clinical impact. Lastly, although cardiotoxicity remains a clinically significant toxicity for all anti-HER2 therapies, novel agents such as T-DM1 seem to have a reduced potential to cause it [33]. Nevertheless, these findings should be considered with caution as patients from clinical trials are highly selected and not always fully representative of patients seen in clinical practice.…”

Section: Safety Of Trastuzumab Emtansinementioning

confidence: 99%

Late Administration of Trastuzumab Emtansine Might Lead to Loss of Chance for Better Outcome in Patients with HER2-Positive Metastatic Breast Cancer

et al. 2018

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The optimal sequence of anti-human epidermal growth factor receptor 2 (HER2) therapies in metastatic breast cancer (MBC) is still undetermined. Physicians must therefore make decisions based on clinical trials and their own experience for the best treatment sequence in these patients. The objective of this review is to summarize the efficacy and safety data for trastuzumab emtansine (T-DM1) in patients with MBC. Additionally, the concept of ‘loss of chance for a better outcome' is investigated. It applies to patients who are not receiving the best possible treatment for their disease. Physicians should strive to offer the best possible care, although getting optimal results in each individual patient is not guaranteed. Lastly, the number of patients with MBC lost per treatment line is evaluated. We conclude that both concepts reinforce the importance of giving the most active treatments as soon as possible in the course of disease to secure the longest possible survival for HER2-positive MBC patients.

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“…As we now have over two decades of experience administering trastuzumab, there is significant information available regarding the rates, timing, and long-term outcomes of trastuzumab-related cardiotoxicity (19). In addition, patient and treatment characteristics that increase risk are well characterized.…”

Section: Incidence Timing and Risk Factors For Trastuzumab-related mentioning

confidence: 99%

Incidence, Diagnosis, and Treatment of Cardiac Toxicity From Trastuzumab in Patients With Breast Cancer

Nowsheen

Viscuse

O’Sullivan

et al. 2017

Curr Breast Cancer Rep

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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. Because trastuzumab-induced cardiotoxicity is typically reversible, cessation of trastuzumab and/or administration of first line heart failure agents effectively restores cardiac function in most cases. Severe trastuzumab-induced cardiotoxicity is rare enough that the risk-benefit ratio still weighs in favor of its use in the vast majority of patients with HER2+ breast cancer. Summary An improved understanding of the pathophysiology underlying trastuzumab-induced cardiotoxicity and the identification of patients at highest risk will allow us to continue to safely administer trastuzumab in patients with breast cancer.

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Twenty years of anti-HER2 therapy-associated cardiotoxicity

Cited by 85 publications

References 127 publications

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

Late Administration of Trastuzumab Emtansine Might Lead to Loss of Chance for Better Outcome in Patients with HER2-Positive Metastatic Breast Cancer

Incidence, Diagnosis, and Treatment of Cardiac Toxicity From Trastuzumab in Patients With Breast Cancer

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