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HER2+ breast cancer treatment and cardiotoxicity: monitoring and management.

ABSTRACT: BACKGROUND:Breast cancer is a leading cause of death for women worldwide, with incidence increasing in lower-income countries. For patients with human epidermal growth factor receptor-2-positive (HER2+) breast cancer, widespread availability of several agents targeting the HER2 receptor has resulted in survival gains over the past decades. However, improved survival has resulted in an increased need for management and mitigation of adverse events associated with anticancer therapy. Cardiac adverse events such as decreased ejection fraction and heart failure have been of particular concern in patients with HER2+?breast cancer. Anti-HER2 agents and chemotherapies (specifically anthracyclines, which are frequently used to treat HER2+?disease) have been associated with cardiotoxicity. As increasing numbers of patients are living longer due to more effective therapy, a better understanding of both monitoring and management of cardiotoxicity is urgently needed. METHODS:A comprehensive review of the literature was conducted via PubMed in January 2018 for phase II and phase III trials of "trastuzumab", "lapatinib", "pertuzumab", "T-DM1", "neratinib", in "breast cancer". Literature was evaluated for content related to cardiac adverse events. FINDINGS:We describe the incidence of and proposed mechanisms for the cardiotoxicity of available HER2-targeted therapies. We summarize current and emerging practices in the management of cardiotoxicity and provide guidance for routine patient care in real-world practice using illustrative patient scenarios. CONCLUSIONS:The future of cardiotoxicity management in patients with HER2+?breast cancer is discussed, with a focus on novel techniques to improve cardiac outcomes, including new imaging modalities, biomarkers, interventional therapies, and ongoing trials.

SUBMITTER: Jerusalem G

PROVIDER: S-EPMC6661020 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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HER2+ breast cancer treatment and cardiotoxicity: monitoring and management.

Jerusalem Guy G Lancellotti Patrizio P Kim Sung-Bae SB

Breast cancer research and treatment 20190605 2

<h4>Background</h4>Breast cancer is a leading cause of death for women worldwide, with incidence increasing in lower-income countries. For patients with human epidermal growth factor receptor-2-positive (HER2+) breast cancer, widespread availability of several agents targeting the HER2 receptor has resulted in survival gains over the past decades. However, improved survival has resulted in an increased need for management and mitigation of adverse events associated with anticancer therapy. Cardi ...[more]

PMID: 31165940

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Project description:OBJECTIVES:This study sought to determine the rate of chemotherapy-related cardiotoxicity and to estimate adherence to recommendations for cardiac monitoring among breast cancer patients treated with chemotherapy. BACKGROUND:Heart failure (HF) is a known complication associated with cancer therapies. Little is known regarding the rate of chemotherapy-related cardiotoxicity and adherence to recommendations for cardiac monitoring among chemotherapy-treated breast cancer patients. METHODS:Patients >18 years of age with a diagnosis of nonmetastatic invasive breast cancer between 2009 and 2014, treated with chemotherapy within 6 months of their diagnosis, were identified in the Truven Health MarketScan (IBM Watson Health, Cambridge, Massachusetts) database. HF, comorbidities, and treatment details were identified using diagnosis and billing codes. Analyses included descriptive statistics, Cox proportional hazard regression, and logistic regression. RESULTS:A total of 16,456 patients were included; the median age was 56 years old. Cardiotoxicity was identified in 4.2% of patients. Therapy with trastuzumab (hazard ratio [HR]: 2.01; 95% confidence interval [CI]: 1.72 to 2.36) and anthracyclines (HR: 1.53; 95% CI: 1.30 to 1.80), Deyo comorbidity scores (HR: 1.38; 95% CI: 1.15 to 1.66; HR: 2.47; 95% CI: 1.94 to 3.15 for scores of 1 and ?2, respectively), hypertension (HR: 1.28, 95% CI: 1.09 to 1.51), and valve disease (HR: 1.93; 95% CI: 1.48 to 2.51) were associated with an increased risk of cardiotoxicity. Patients ?35 years of age (HR: 0.37; 95% CI: 0.19 to 0.72) and 36 to 49 years of age (HR: 0.49; 95% CI: 0.38 to 0.62) were less likely to have cardiotoxicity than patients 65 years of age and older. Among 4,325 patients treated with trastuzumab, guideline-adherent cardiac monitoring was identified in 46.2% of patients. Therapies using anthracyclines (odds ratio [OR]: 1.58; 95% CI: 1.35 to 1.87), taxanes (OR: 1.63; 95% CI: 1.27 to 2.08), and radiation (OR: 1.22; 95% CI: 1.08 to 1.39) were associated with guideline-adherent monitoring. CONCLUSIONS:HF is an uncommon complication of breast cancer therapies. The risk was higher among patients treated with trastuzumab or anthracyclines and lower in younger patients. Cardiac monitoring among trastuzumab-treated patients should be a priority among high-risk patients and in the presence of comorbidities or other chemotherapies such as those using anthracyclines.

Project description:BackgroundBreast cancer treatment is associated with the occurrence of various cardiac adverse events. One of the mechanisms associated with cardiotoxicity is oxidative stress, against which cells are protected by antioxidative enzymes. Genetic variability of antioxidative enzymes can affect enzyme activity or expression, which modifies the ability of cells to defend themselves against oxidative stress and could consequently contribute to the occurrence of treatment-related cardiotoxicity. Our aim was to evaluate the association of common polymorphisms in antioxidative genes with cardiotoxicity after adjuvant radiotherapy (RT) in HER2-positive breast cancer patients.MethodsOur retrospective study included 101 HER2-positive early breast cancer patients who received trastuzumab and adjuvant RT. We isolated DNA from buccal swabs and used competitive allele-specific PCR for genotyping of PON1 rs854560 and rs662, GSTP1 rs1138272 and rs1695, SOD2 rs4880, CAT rs1001179, and HIF1 rs1154965 polymorphisms. N-terminal pro B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction, and NYHA class were used as markers of cardiotoxicity. We used logistic regression to evaluate the association of genetic factors with markers of cardiotoxicity.ResultsCarriers of at least one polymorphic PON1 rs854560 allele were less likely to have increased NT-proBNP (OR = 0.34; 95% CI = 0.15-0.79; P = 0.012), even after adjustment for age (OR = 0.35; 95% CI = 0.15-0.83; P = 0.017). Carriers of at least one polymorphic PON1 rs662 allele were more likely to have increased NT-proBNP (OR = 4.44; 95% CI = 1.85-10.66; P = 0.001), even after adjustment for age (OR = 5.41; 95% CI = 2.12-13.78; P < 0.001). GSTP1 rs1695 was also associated with decreased NT-proBNP in the multivariable analysis (P = 0.026), while CAT rs1001179 was associated with NYHA class in the univariable (P = 0.012) and multivariable analysis (P = 0.023).ConclusionIn our study, polymorphisms PON1 rs662 and rs854560, CAT rs1001179, and GSTP1 rs1695 were significantly associated with the occurrence of cardiac adverse events after adjuvant RT and could serve as biomarkers contributing to treatment personalization.

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HER2+ breast cancer treatment and cardiotoxicity: monitoring and management.

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HER2+ breast cancer treatment and cardiotoxicity: monitoring and management.

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