Age significantly influences the severity of chemotherapy-induced cardiotoxicity (cardiotoxicity) in HER2-positive breast cancer patients. Comprehensive cardiac monitoring before, during, and after anthracycline and trastuzumab regimens is essential. Tailored assessments can help identify vulnerable patients, optimize treatment, and mitigate risks of heart complications while maintaining therapy efficacy.

Cardiotoxicity has become a major concern in cancer patients, especially those with lung cancer, as anti-tumor therapies can significantly affect patient survival and quality of life. This study aims to develop and validate a dynamic nomogram based on the Inflammation Burden Index (IBI) to predict the risk of cardiac injury within one year after anti-tumor treatment in lung cancer patients.

This single-center, retrospective study included 1386 lung cancer patients who underwent myocardial enzyme testing between July 2018 and January 2023. The IBI was calculated as: IBI = (CRP (mg/dL) × Neutrophils (/μL)) / Lymphocytes (/μL). Statistical analysis using SPSS 22.0 and R 4.4.1, including machine learning algorithms and multivariate logistic analysis, identified independent predictors of cardiac injury. An online dynamic nomogram was developed and validated using internal validation, ROC curves, and decision curve analysis (DCA).

The average age of the 1386 patients was 61.98 ± 9.22 years. Significant independent predictors included age, BMI, hypertension, immunotherapy, D-dimer, LDH, NSE, CKMB, and IBI. The nomogram showed strong discriminative ability with AUC-ROC values of 0.85 for the training set and 0.86 for the validation set. Calibration curves confirmed good fit, and DCA showed high clinical utility.

An online dynamic nomogram based on clinical and inflammatory markers was developed to predict cardiac injury in lung cancer patients following anti-tumor therapy. The model shows strong discriminative ability and potential clinical value, which can provide vital information for oncologists when designing customized clinical treatments.

IntroductionExperts suggest doxorubicin clearance is decreased in women with a body mass index (BMI) of ≥35 kg/m2. However, few data support this recommendation.MethodsWomen receiving doxorubicin for breast cancer in three BMI groups were recruited (n = 15). Doxorubicin dosing was determined by body surface area and was administered by 30-min intravenous infusion. Blood samples were obtained at 0 h (pre-dose) and 0.5, 1, 1.5, 2, 3, 4, 5, 12-24, and 24-72 h following the beginning of infusion. Concentrations of doxorubicin and its metabolite, doxorubicinol, were assayed by LC-MS/MS. Non-compartment analysis was done using PKanalix2021R2 for pharmacokinetic (PK) analyses.ResultsThe median [range] BMI and age were 30.3 [23.5-57] kg/m2 and 53 [31-69] years. Thirteen of the 15 women had samples available for analysis. Four of the 13 had a BMI ≥ 35.0 kg/m2. PK parameters ranged from 37.8% (AUC0-inf) to 91.0% (Vd). Doxorubicinol PK parameters ranged from 37.8% (Cmax) to 67.6% (AUC0-inf). The average doxorubicinol:doxorubicin AUClasts ratio was 0.26 (range: 0.04-0.88). A t-test didn't suggest a significant difference in individual PK parameters (BMI < 35 kg/m2 vs. ≥35.0 kg/m2). The two highest clearances (380 L/h and 250 L/h) had a BMI ≥ 35.0 kg/m2; also, the highest clearance (1114 L/h) for doxorubicinol was ≥35.0 kg/m2.ConclusionsLarge interindividual variabilities in doxorubicin PK were observed in women up to a BMI of 57 kg/m2 and a total body weight of 141.5 kg. Women with a BMI ≥ 35.0 kg/m2 and breast cancer did not appear to have lower clearances of doxorubicin.ClinicalTrials.gov IDNCT01537029.

Breast cancer is one of the leading causes of malignancy affecting women in the United States. Although many effective treatments are available, most come with notable side effects that providers and patients must take into consideration. Various classes of chemotherapeutic agents, including anthracyclines and human epidermal growth factor receptor-2 antagonists, are known to be toxic to myocardial tissue. In this review article, we discuss what is reported in the literature regarding the cardiotoxicity of these agents as well as how to monitor and prevent cardiac injury and dysfunction.

Introduction: Obesity is a chronic disease associated with increased risk for several cancers, including colorectal cancer (CRC), a leading cause of cancer-related mortality. The majority of CRC cases are associated with modifiable risk factors. Metabolic and bariatric surgery (MBS) is a proven, durable, and successful intervention for obesity. This study aimed to evaluate the impact of MBS on CRC risk through measures of association, such as relative risk (RR) and odds ratio (OR). Methods: A systematic search of PubMed, Scopus, Web of Science, ScienceDirect, and Embase was conducted to identify systematic reviews (SR) and meta-analyses examining the relationship between obesity treated with MBS and CRC incidence. The PICO framework guided inclusion criteria, and three independent reviewers screened articles using Rayyan software. Quality assessment was performed using AMSTAR2. Results: Of 1336 screened articles, 10 SR met inclusion criteria, encompassing 53,452,658 patients. Meta-analyses consistently showed a significant reduction in CRC risk following MBS in patients with severe obesity. Risk reductions were reported by Liu et al. (RR: 0.46, 95% CI: 0.32-0.67, p < 0.01), Chierici et al. (RR: 0.46, 95% CI: 0.28-0.75, p = 0.018), Wilson et al. (RR: 0.69, 95% CI: 0.53-0.88, p = 0.003), and Pararas et al. (RR: 0.56, 95% CI: 0.40-0.80, p < 0.001). Sensitivity analyses supported these findings. For colon cancer, Liu and Chierici both reported an RR of 0.75 (95% CI: 0.46-1.21, p = 0.2444) with significant heterogeneity (I2 = 89%). A trend towards reduced rectal cancer risk (RR: 0.74, 95% CI: 0.40-1.39, p = 0.3523) was noted but limited by fewer studies. Sex-specific analyses revealed protective effects in both sexes, with a more pronounced impact in females (RR: 0.54, 95% CI: 0.37-0.79, p = 0.0014). Conclusions: This umbrella review synthesizes current evidence on the impact of MBS on CRC risk, highlighting a consistent protective association. The findings also indicate a potential risk reduction for both colon and rectal cancer, with a more pronounced effect observed among females compared to males. Given the profound implications of MBS on cancer incidence, morbidity, and mortality, further high-quality, long-term studies are essential to deepen our understanding and optimize its role in cancer prevention and patient care.

Breast cancer is a major health challenge for women worldwide, and human epidermal growth factor receptor 2 (HER-2)-positive breast cancers have a relatively high incidence and are highly aggressive. Targeted therapeutic agents, represented by trastuzumab, have been effective in improving the survival rate of HER-2-positive breast cancer patients. However, in clinical applications, this type of targeted drugs exhibits varying degrees of cardiotoxicity, and the mechanism of their cardiotoxicity is currently unclear. In this paper, we classify them into three categories: monoclonal antibodies (mAbs), small-molecule tyrosine kinase inhibitors (TKIs), and antibody-drug conjugate (ADCs). We list the evidence of cardiotoxicity for various drugs based on current clinical trials and summarize their corresponding epidemiological profiles. We also discuss the regulation of cardiotoxicity from three perspectives: clinical biomarkers of cardiotoxicity, permissive cardiotoxicity, and the current status of cardiotoxicity regulation.

Assessment of cardiac disease before cancer therapy is crucial, as advancements in cancer treatment have led to prolonged survival and an increase in cardiovascular complications. Specifically, esophageal cancer and heart disease share common risk factors, such as smoking and obesity. Radiation therapy (RT) for esophageal cancer is associated with elevated cardiac radiation exposure. This study aimed to assess the prevalence of coronary artery disease (CAD) in patients with esophageal cancer who were eligible for RT.

We examined the prevalence of coronary artery stenosis, abnormal myocardial perfusion, and late enhancement using pre-RT cardiac computed tomography (CT) data of 41 patients with thoracic esophageal cancer who were referred for RT between January 2017 and June 2023 and had no history of ischemic heart disease.

The median age of the 41 patients was 71 years, with 40 patients being male. Cardiac CT identified significant coronary stenosis (≥50% luminal narrowing) in 18 patients (44%), among whom 9 (50%) had severe stenosis, multivessel disease, or myocardial ischemia. Significant stenosis was most frequently observed in the left anterior descending artery (16/18). Late enhancement, indicating myocardial infarction, was observed in seven patients (17%).

Patients with esophageal cancer without a history of ischemic heart disease had a high prevalence (44%) of CAD, with half of them having severe stenosis, multivessel disease, or myocardial ischemia. Given the high prevalence of coronary stenosis, pre-treatment cardiac evaluation is crucial for patients with esophageal cancer. Incorporating cardiac CT findings into radiotherapy planning is recommended to optimize patient care.

Anthracycline usage has been linked to cardiovascular adverse events (CAEs), which is unpredictable. It is critical to identify the characteristics of vulnerable populations and risk factors in order to reduce the occurrence of CAEs.

This meta-analysis aimed to assess the correlation between various risk factors and CAEs induced by anthracyclines.

We systematically searched for studies from PubMed, Cochrane, Embase, and assessed the publication bias. Anthracyclines, hypertension, radiation therapy, diabetes, smoking, age, gender, hyperlipidemia, and obesity were meta-analyzed using a fixed or random effects model.

Sixteen studies were included in this meta-analysis. The results showed that pooled relative ratio for CAEs was 1.69 (95% CI: 1.39-2.06, p<0.001) for anthracyclines, and that risk factors for CAEs caused by anthracyclines included hypertension (RR = 2.15, 95% CI: 1.53-3.01, p < 0.001), radiation therapy (RR = 1.71, 95% CI: 1.19-2.47, p < 0.001), diabetes (RR = 1.57, 95% CI: 1.20-2.06, p<0.001), smoking (RR = 1.35, 95% CI: 0.96-1.88, p < 0.05), and age (RR = 1.16, 95% CI: 1.07-1.26, p < 0.001). In addition, BMI > 25 kg/m2 (RR = 1.34, 95% CI: 1.08-1.67, p = 0.470), gender (RR = 1.17, 95% CI: 1.06-1.2, p = 0.350), and hyperlipidemia (RR = 1.10, 95% CI: 0.91-1.34, p = 0.327) was not significantly associated with CAEs caused by anthracyclines.

Our research findings indicate that patients with a history of hypertension, radiation therapy, diabetes, smoking, and elderly individuals are at an elevated risk of cardiovascular disease in the process of administration of anthracycline drugs. Consequently, careful case selection and condition monitoring are important in the treatment process.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

Strong evidence supports the benefits of exercise following both cardiovascular disease and cancer diagnoses. However, less than one-third of Australians who are referred to exercise rehabilitation complete a program following a cardiac diagnosis. Technological advances make it increasingly possible to embed real-time supervision, tailored exercise prescription, behavior change, and social support into home-based programs.

This study aimed to explore demographic and health characteristics associated with the likelihood of breast cancer survivors uptaking a digitally delivered cardiac exercise rehabilitation program and to determine whether this differed according to intervention timing (ie, offered generally, before, during, or after treatment). Secondary aims were to explore the knowledge of cardiac-related treatment side-effects, exercise behavior, additional intervention interests (eg, diet, fatigue management), and service fee capabilities.

This cross-sectional study involved a convenience sample of breast cancer survivors recruited via social media. A self-reported questionnaire was used to collect outcomes of interests, including the likelihood of uptaking a digitally delivered cardiac exercise rehabilitation program, and demographic and health characteristics. Descriptive statistics were used to summarize sample characteristics and outcomes. Ordered logistic regression models were used to examine associations between demographic and health characteristics and likelihood of intervention uptake generally, before, during, and after treatment, with odds ratios (ORs) <0.67 or >1.5 defined as clinically meaningful and statistical significance a priori set at P≤.05.

A high proportion (194/208, 93%) of the sample (mean age 57, SD 11 years; median BMI=26, IQR 23-31 kg/m2) met recommended physical activity levels at the time of the survey. Living in an outer regional area (compared with living in a major city) was associated with higher odds of uptake in each model (OR 3.86-8.57, 95% CI 1.04-68.47; P=.01-.04). Receiving more cardiotoxic treatments was also associated with higher odds of general uptake (OR 1.42, 95% CI 1.02-1.96; P=.04). There was some evidence that a higher BMI, more comorbid conditions, and lower education (compared with university education) were associated with lower odds of intervention uptake, but findings differed according to intervention timing. Respondents identified the need for better education about the cardiotoxic effects of breast cancer treatment, and the desire for multifaceted rehabilitation interventions that are free or low cost (median Aus $10, IQR 10-15 per session; Aus $1=US $0.69 at time of study).

These findings can be used to better inform future research and the development of intervention techniques that are critical to improving the delivery of a digital service model that is effective, equitable, and accessible, specifically, by enhancing digital inclusion, addressing general exercise barriers experienced by chronic disease populations, incorporating multidisciplinary care, and developing affordable delivery models.

Chemotherapy-induced cardiotoxicity (CIC) is a significant challenge in cancer treatment, leading to heart failure and myocardial infarction. With rising cancer survival rates, the long-term cardiovascular health of survivors has gained importance. While several cardioprotective medications have been studied to mitigate chemotherapy's harmful effects on the heart, more research is needed to confirm their effectiveness and optimal use.

This review synthesizes evidence on cardioprotective drugs in managing CIC. The authors conducted a comprehensive literature search of peer-reviewed articles, clinical trials, and meta-analyses published between January 2000 and May 2024. Studies were selected based on relevance, quality, and focus on mechanisms, efficacy, and clinical outcomes of cardioprotective agents such as beta-blockers, ACE inhibitors, ARBs, statins, and dexrazoxane.

Cardioprotective medications show potential in alleviating the impact of chemotherapy on heart function. Beta-blockers and ACE inhibitors effectively reduce heart failure incidence and improve cardiac outcomes. Statins, with their anti-inflammatory and antioxidative properties, and dexrazoxane, which reduces anthracycline-induced cardiotoxicity, also show promise. However, variability in study designs, patient groups, and chemotherapy treatments complicates the establishment of standardized treatment protocols.

Cardioprotective drugs hold significant promise in managing CIC and improving cardiac outcomes for cancer patients. Current evidence supports the efficacy of beta-blockers, ACE inhibitors, statins, and dexrazoxane. Further research is needed to establish standardized protocols, evaluate long-term safety, and optimize treatment timing. Integrating cardioprotective strategies into oncological care can enhance the quality of life and prognosis for cancer survivors.

Medicago sativa L. is gaining attention as a sustainable plant-based food protein. Alfalfa saponins (ASs) typically exist in a glycosylated form in nature, which has poor cell membrane permeability, while the deglycosylated saponins may show better bioactivity. The AS was deglycosylated by β-glucosidase from Aspergillus niger, and the chemical structures and biological activities, including in vivo assays, of AS and deglycosylated AS (DAS) were determined. The results showed that the half maximal inhibitory concentration for 2,2-diphenyl-1-picrylhydrazyl inhibition of DAS was 29.5 µg/mL, demonstrating a significantly higher reducing capacity compared to AS (p < 0.05). The DAS induced 33.8% antibacterial activity against Escherichia coli and enhanced the proliferation of human airway epithelial cells (BEAS-2B) at a concentration of 125 µg/mL. In vivo experiments on C57BL/6 mice fed a high-fat diet demonstrated that high-level DAS treatment produced significantly greater hypolipidemic effects compared to AS (p < 0.05). Thus, the AS can be deglycosylated, which leads to an improvement in biological activity, particularly since the DAS exhibits significantly enhanced hypolipidemic activity. PRACTICAL APPLICATION: Alfalfa saponins were deglycosylated by β-glucosidase from Aspergillus niger, which contributed to increased bioactivity, particularly its hypolipidemic activity.

Epidemiology studies have demonstrated a clear association between obesity and the development of several distinct malignancies, with excessive visceral adiposity being an increasingly prevalent feature in patients with cancer presenting for therapeutic intervention. Clinical trials and meta-analyses have helped to inform effective and safe dosing of traditional systemically administered anticancer agents in adult patients with cancer and obesity, but there remains much debate not only regarding the effect of obesity on the more novel targeted molecular and immune-based therapies, but also about how obesity is best defined and measured clinically. Low muscle mass is associated with poor outcomes in cancer, and body composition studies using biochemical and imaging modalities are helping to fully delineate the importance of both obesity and sarcopenia in clinical outcomes; such studies might also go some way to explaining how obesity can paradoxically be associated with favourable clinical outcomes in certain cancers. As the cancer survivorship period increases and the duration of anticancer treatment lengthens, this Review highlights the challenges facing appropriate treatment selection and emphasizes how a multidisciplinary approach is warranted to manage weight and skeletal muscle loss during and after cancer treatment.

Anthracyclines are essential in pediatric cancer treatment, but patients are at risk cancer therapy-related cardiac dysfunction (CTRCD). Standardized definitions by the International Cardio-Oncology Society (IC-OS) aim to enhance precision in risk assessment.

Categorize distinct phenotypes among pediatric patients undergoing anthracycline chemotherapy using unsupervised machine learning.

Pediatric cancer patients undergoing anthracycline chemotherapy at our institution were retrospectively included. Clinical and echocardiographic data at baseline, along with follow-up data, were collected from patient records. Unsupervised machine learning was performed, involving dimensionality reduction using principal component analysis and K-means clustering to identify different phenotypic clusters. Identified phenogroups were analyzed for associations with CTRCD, defined following contemporary IC-OS definitions, and hypertensive response.

A total of 187 patients (63.1% male, median age 15.5 years [10.4-18.7]) were included and received anthracycline chemotherapy with a median treatment duration of 0.66 years [0.35-1.92]. Median follow-up duration was 2.78 years [1.31-4.21]. Four phenogroups were identified with following distribution: Cluster 0 (32.6%, n = 61), Cluster 1 (13.9%, n = 26), Cluster 2 (24.6%, n = 46), and Cluster 3 (28.9%, n = 54). Cluster 0 showed the highest risk of moderate CTRCD (HR: 3.10 [95% CI: 1.18-8.16], P = 0.022) compared to other clusters. Cluster 3 demonstrated a protective effect against hypertensive response (HR: 0.30 [95% CI: 0.13- 0.67], P = 0.003) after excluding baseline hypertensive patients. Longitudinal assessments revealed differences in global longitudinal strain and systolic blood pressure among phenogroups.

Unsupervised machine learning identified distinct phenogroups among pediatric cancer patients undergoing anthracycline chemotherapy, offering potential for personalized risk assessment.

Trastuzumab is primarily utilized in the treatment of patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer. This study aimed to investigate the incidence of cardiac toxicity associated with trastuzumab in HER2-positive breast cancer patients at Iran Hospital in 2023, as well as the factors influencing this toxicity. In this cross-sectional study, 200 patients diagnosed with HER2-positive breast cancer and receiving trastuzumab were included. The criteria for heart failure in this study were defined as an ejection fraction (EF) of less than 50% or a decrease of greater than 10% in EF. Descriptive statistics, the chi-square statistical test, Fisher's exact test, and logistic regression analyses were employed to assess the variables. A p-value of less than 0.05 was deemed statistically significant. The mean age of the participants was 51.5 ± 2.5 years. The odds ratio (OR) for the variable of anthracyclines was 1.3 (95% CI: 1.2-1.4); for opium use, the OR was 2.7 (95% CI: 0.9-8.5); for diabetes, the OR was 2.7 (95% CI: 1.2-5.9); for ischemic heart disease, the OR was 3.5 (95% CI: 1.6-7.7); and for hypertension, the OR was 4.8 (95% CI: 2.1-10.7). The OR for obesity was 1.45 (95% CI: 1.01-2.18), and the OR for age was 1.10 (95% CI: 1.01-1.12). No statistically significant association was found between opium use and cardiotoxicity (p = 0.07). This research contributes to the identification of factors that may predict responses to anthracyclines and the potential for cardiotoxicities. Ultimately, this information could inform the development of more personalized treatment strategies.

Chemotherapy associated with breast cancer often induces cardiotoxicity, which compromises patients' health and quality of life.

To verify the effect of physical exercise on chemotherapy-induced cardiotoxicity, through the assessment of cardiac function in patients with breast cancer.

A systematic review and meta-analysis of clinical studies was conducted to evaluate the effectiveness of physical training in chemotherapy-induced cardiomyopathy in the PubMed, Web of Sciences and Scopus databases. Thirteen studies were included in the systematic review and eleven studies in the data meta-analysis.

Global longitudinal strain presents a cardioprotective effect when compared to the control group (Heterogeneity: Chi² = 12.81, df = 10 (p = 0.23); I² = 22 %.) Test for global effect: Z = 2, 13 (p = 0.03). Physical training is more effective (test for subgroup differences, p = 0.031) in attenuating the impairment of %GLS induced by chemotherapy if performed concomitantly with exposure to chemotherapy (95 % CI; Heterogeneity: Chi² = 7.49, gl = 5 (p = 0.19); I² = 33 %; Test for global effect: Z = 2.33 (p = 0.02) when compared after chemotherapy treatment, or in the long term (for 12 months or more). However, without benefits in LVEF (Heterogeneity: Chi² = 42.14, df = 10 (p < 0.00001); I² = 76 %) Test for global effect: Z = 2.51 (p = 0.01) Conclusion: Exercise training is a cardioprotective approach in breast cancer patients who experience chemotherapy-induced cardiotoxicity. Exercise during exposure to chemotherapy has greater effects on preserving cardiac function.

Doxorubicin (DOX) has been widely used in the treatment of breast cancer, but it is directly associated with late-onset cardiovascular disease (CVD). Whether anthropometric, food intake or other risk factors together with DOX-based chemotherapy can increase the risk of developing cardiotoxicity remains uncertain. We examined the association between anthropometric variables with doxorubicin-induced cardiotoxicity in women with breast cancer.

Twenty-six women (53.7 ± 9.6 y) undergoing DOX-based chemotherapy (408.3 ± 66.7 mg/m2) participated in the study. We collected data on body composition (bioimpedance), dietary intake (24 h) and cardiac function (echocardiographic assessment of left ventricular ejection fraction, LVEF). All measurements were taken at baseline, one month of treatment completion and one-year follow-up after start of treatment. DOX-induced cardiotoxicity was defined as ≥ 10% absolute decrease in LVEF. Thus, the participants were then grouped as DOX-induced (DIC) or non-DOX-induced (non-DIC) cardiotoxicity. Data are shown as mean ± SD (standard deviation). We performed comparisons between the two groups using Student's t-test for independent samples or Generalized Estimating Equations (groups + 3 evaluation time points) with Bonferroni post-hoc test. Lastly, the correlations were analyzed using Pearson correlation; p < 0.05 for all tests.

At baseline the participants' body mass index (BMI) was 29.9 ± 7.9 kg/m2 and LVEF was 67.4 ± 6.2%. Seven of them (26.9%) developed therapy-induced cardiotoxicity (ΔLVEF - 3.2 ± 2.6%; p < 0.001). Postmenopausal status and family history of CVD were more prevalent in the DIC group than non-DIC group. We found no consistent BMI changes in the groups over time. Interestingly, the non-DIC group showed a small increase in visceral fat at treatment completion and increased waist circumference at one-year follow-up compared to baseline. These same changes were not seen in the DIC group. We also observed a pattern of correlation of some anthropometric variables with LVEF: the more unfavorable the body composition the more pronounced the LVEF decrease at one-year follow-up, though not associated with cardiotoxicity.

Our study did not provide sufficient evidence to support that anthropometric variables, food intake or other risk factors increase the risk of developing cardiotoxicity. However, there are apparent trends that need to be further investigated in larger samples.

Many cardiovascular diseases are characterized by diastolic dysfunction, which associates with worse clinical outcomes like overall mortality and hospitalization for heart failure (HF). Diastolic dysfunction has also been suspected to represent an early manifestation of cardiotoxicity induced by cancer drugs, with most of the information deriving from patients treated with anthracyclines; however, the prognostic implications of diastolic dysfunction in the anthracycline-treated patient have remained poorly explored or neglected. Here the molecular, pathophysiologic and diagnostic aspects of anthracycline-related diastolic dysfunction are reviewed in the light of HF incidence and phenotype in cancer survivors. We describe that the trajectories of diastolic dysfunction toward HF are influenced by a constellation of patient- or treatment- related factors, such as comorbidities and exposure to other cardiotoxic drugs or treatments, but also by prospective novel opportunities to treat diastolic dysfunction. The importance of a research-oriented multidimensional approach to patient surveillance or treatment is discussed within the framework of what appears to be a distinct pathophysiologic entity that develops early during anthracycline treatment and gradually worsens over the years.

Cardiotoxic chemotherapy is used to treat malignancies such as breast cancer and lymphoma. These treatments predispose patients to cardiotoxicity that can lead to cancer treatment-related cardiac dysfunction (CTRCD). The use of high doses of anthracyclines or in combination with human epidermal growth factor receptor 2 antagonists is associated with a progressively higher risk of CTRCD. CTRCD is preceded by increased activation of the sympathetic nervous system and abnormal left ventricular mechanical deformation as measured by abnormal global longitudinal strain (GLS). Low-level tragus stimulation (LLTS) is a new, safe, noninvasive technique that offers great potential to reduce increased sympathetic activation and improve GLS. Here, we describe a study method to examine the effects of LLTS on autonomic balance and cardiac function in breast cancer or lymphoma patients treated with anthracyclines.

A first-in-human pilot, randomized, double-blind feasibility study will evaluate 104 patients (age >50 y) with breast cancer or lymphoma who receive anthracyclines with one additional CTRCD risk factor. Patients undergo 2 weeks of LLTS daily (1 h/d). Autonomic balance will be measured using heart rate variability metrics. Strain imaging using GLS will be performed pre and post-LLTS. Endothelial inflammation and oxidative stress measures will be performed using in vitro assays at baseline and after 2 weeks.

We hypothesize that LLTS stabilizes sympathovagal imbalance and improves cardiac performance in anthracycline-treated patients with breast cancer or lymphoma.

Female sex is frequently cited as a risk factor for anthracycline cardiotoxicity based on pediatric data, but the role of sex in the development of cardiotoxicity has not been clearly established in adults.

To assess the effect of female sex on the development of incident heart failure (HF) in adult patients treated with anthracyclines.

This was a retrospective cohort study of 1525 adult patients with no prior history of HF or cardiomyopathy who were treated with anthracyclines between 1992 and 2019. The primary outcome was new HF within 5 years of the first dose of anthracyclines. The effect of sex was assessed using Cox proportional hazards and competing risk models.

Over a median (IQR) follow-up of 1.02 (0.30-3.01) years, 4.78% of patients developed HF (44 men and 29 women). Female sex was not associated with the primary outcome in a multivariable Cox proportional hazards model (HR 0.87; 95% CI 0.53-1.43; P = 0.58). Similar results were observed in a multivariable model accounting for the competing risk of death (HR 0.94; 95% CI 0.39-2.25; P = 0.88). Age, coronary artery disease and hematopoietic stem cell transplant were associated with the primary outcome in a multivariable Cox proportional hazards model. Age and body mass index were associated with the primary outcome in a multivariable competing risk model.

In this large, single-center, retrospective cohort study, female sex was not associated with incident HF in adult patients treated with anthracyclines.

Female sex is frequently cited as a risk factor for anthracycline cardiotoxicity based on pediatric data, but the role of sex in the development of cardiotoxicity has not been clearly established in adults. In this retrospective cohort study, we assessed the effect of female sex on the development of incident heart failure in adult patients treated with anthracyclines. Using Cox proportional hazards and competing risk regression models, we found that there was no association between female sex and heart failure after treatment with anthracyclines.

To understand how body composition in those with elevated body mass index impacts left ventricular function decline during cancer treatment, we determined the association between baseline body mass index (BMI), intra-abdominal adipose tissue (IAT) and subcutaneous adipose tissue (SAT) with baseline to 3-month left ventricular ejection fraction (LVEF) change among women receiving potentially cardiotoxic chemotherapy for breast cancer, lymphoma, or sarcoma.

Women underwent potentially cardiotoxic chemotherapy, such as doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab, for treatment of breast cancer, lymphoma, or sarcoma. We obtained magnetic resonance images (MRIs) of body composition and cardiac function prior to treatment, and then a repeat MRI for cardiac function assessment at three months into treatment. Analyses and assessment of abdominal adipose tissue volumes and LVEF outcomes were conducted by independent reviewers blinded to all patient identifiers. A general linear model was created to examine associations between adipose tissue depots, BMI, and 3-month LVEF change.

Women (n = 210) aged 56 ± 11 years with breast cancer, lymphoma, and sarcoma were enrolled (n = 195, 14, 1 respectively). Baseline BMI, IAT, and SAT fat were independently associated with 3-month LVEF declines (p = 0.001 to 0.025 for all). After adjusting for baseline cardiovascular disease risk factors, BMI, IAT, and SAT, BMI remained the only variable associated with 3-month LVEF decline (p = 0.047).

These results suggest that factors other than abdominal adipose tissue or traditional cardiovascular risk factors may contribute to 3-month declines in LVEF among women with elevated BMI receiving potentially cardiotoxic chemotherapy. Further investigation should be conducted on psychosocial stress, physical activity, sleep, or diet.

DETECTIV_NCT01719562, WF99112, & WF97415-NCT02791581.

The benefits in survivorship gained with anthracycline (ANT)-based chemotherapies for breast cancer are unfortunately mitigated for some patients by irreversible cardiotoxicity. Randomised controlled trials (RCTs) have explored multiple cardioprotection options, however, it remains unclear which drug is most effective in preserving left ventricular ejection fraction (LVEF). This study aimed to perform a systematic review and network meta-analysis, using Bayesian and frequentist approaches, of RCTs evaluating cardioprotective agents.

Two authors searched four databases (CENTRAL, Cochrane Reviews, MEDLINE, SCOPUS), to find RCTs evaluating cardioprotective agents. Trial populations were limited to patients with breast cancer without prior ANT exposure. The primary outcome was mean LVEF change pre and post ANT dosing. Our primary analysis utilised a Bayesian approach, while our sensitivity analysis used frequentist methodology (Prospero registration number CRD42020199580).

From 4,007 search results, we identified 12 RCTs, with their various trial arms considered separately-nine beta-blocker (BB), two angiotensin-converting enzyme inhibitor /angiotensin receptor blockers [(AA)+BB=AABB], one AA, one spironolactone, one statin-evaluating 1,126 patients (age 50.5 years). Bayesian network meta-analysis showed no difference in LVEF preservation between AA (1.3%, 95% credible interval [-0.20, 2.9]), BB (0.77, [-0.21, 1.8]), AABB (0.84 [-1.1, 2.8]), spironolactone (0.72, [-2.3, 3.7]) or statin (0.60, [-2.4, 3.6]) when compared against placebo. However, the frequentist analysis showed benefits from using AA (mean difference, 1.32% [0.32, 2.33]) and BB (mean difference, 0.76% [0.12, 1.4]).

There is insufficient evidence to support prophylactic cardioprotection to prevent EF reduction. However, frequentist analysis suggested that AA or BBs provide cardioprotection. Thus, for those already on other anti-hypertensives, switching to AA or BBs could be considered.

Older women with breast cancer frequently experience toxicity-related hospitalizations during adjuvant chemotherapy. Although the geriatric assessment can identify those at risk, its use in clinic remains limited. One simple, low-cost marker of vulnerability in older persons is fall history. Here, the authors examined whether falls prechemotherapy can identify older women at risk for toxicity-related hospitalization during adjuvant chemotherapy for breast cancer.

In a prospective study of women >65 years old with stage I-III breast cancer treated with adjuvant chemotherapy, the authors assessed baseline falls in the past 6 months as a categorical variable: no fall, one fall, and more than one fall. The primary end point was incident hospitalization during chemotherapy attributable to toxicity. Multivariable logistic regression was used to examine the association between falls and toxicity-related hospitalization, adjusting for sociodemographic, disease, and geriatric covariates.

Of the 497 participants, 60 (12.1%) reported falling before chemotherapy, and 114 (22.9%) had one or more toxicity-related hospitalizations. After adjusting for sociodemographic, disease, and geriatric characteristics, women who fell more than once within 6 months before chemotherapy had greater odds of being hospitalized from toxicity during chemotherapy compared to women who did not fall (50.0% vs. 20.8% experienced toxicity-related hospitalization, odds ratio, 4.38; 95% confidence interval, 1.66-11.54, p = .003).

In this cohort of older women with early breast cancer, women who experienced more than one fall before chemotherapy had an over 4-fold increased risk of toxicity-related hospitalization during chemotherapy, independent of sociodemographic, disease, and geriatric factors.

The 2022 ESC Guidelines on Cardio-Oncology recommend baseline cardiovascular risk stratification before starting anticancer drugs, using the new risk assessment tools proposed by the Heart Failure Association (HFA) and the International Cardio-Oncology Society (ICOS).Our study aimed to assess the clinical application of HFA/ICOS risk score in breast cancer patients undergoing chemotherapy and its usefulness in predicting the development of chemotherapy-related cardiac dysfunction (CTRCD).

A prospective multicentric study enrolled 109 breast cancer patients treated with anthracyclines with or without trastuzumab. A cardiological evaluation, including ECG and echocardiogram at baseline (T0), 3 (T1), 6 (T2), and 12 months (T3) after starting treatment was performed. HFA/ICOS score was assessed in all patients. The population was divided into low, medium, high, and very-high risk.During follow-up, CTRCD and other cardiovascular events have been evaluated.

61 patients were low risk, 37 medium, 9 high, 2 very-high risk criteria. We found a significantly higher incidence of overall cardiotoxicity (CTRCD and other cardiovascular events) in the very-high risk group (100%) compared with the medium (29%) and low risk groups (13%). CTRCD incidence was also significantly higher in the high risk group (55%). CTRCD resulted as being associated with baseline arterial hypertension and baseline HFA/ICOS risk score of high ( p  = 0.006) or very-high ( p  < 0.0001).

Our study confirms the HFA/ICOS score's ability to predict cardiovascular toxicity in breast cancer women and the need for close monitoring especially in high and very-high risk patients.

Doxorubicin (DOX) is an anthracycline antibiotic widely used as a chemotherapeutic agent to treat solid tumours and hematologic malignancies. Although useful in the treatment of cancers, the benefit of DOX is limited due to its cardiotoxic effect that is observed in a large number of patients. In the literature, there is evidence that the presence of various factors may increase the risk of developing DOX-induced cardiotoxicity. A better understanding of the role of these different factors in DOX-induced cardiotoxicity may facilitate the choice of the therapeutic approach in cancer patients suffering from various cardiovascular risk factors. In this review, we therefore discuss the latest findings in both preclinical and clinical research suggesting a link between DOX-induced cardiotoxicity and various risk factors including sex, age, ethnicity, diabetes, dyslipidaemia, obesity, hypertension, cardiovascular disease and co-medications.

Monoclonal antibody products are an increasing portion of novel drug approvals. The labeling of initial drug approvals frequently involves body-size-based rather than fixed-dose administration regimens for adults without clear rationale for doing so. This presents challenges when prescribing these products for patients with extremes of body habitus who constitute a small portion of enrollment in pre-approval investigations. Fixed-dose regimens allow for standardized preparation with the potential to reduce the risk of calculation errors, drug waste, and make home administration more practical. Fixed-dose rather than body-size-based monoclonal antibody regimens should serve as the initial approach in early phase 1 clinical trials.

Several studies have suggested that sarcopenia is associated with an increased treatment toxicity in patients with cancer. The aim of this study is to evaluate the relationship between sarcopenia and anthracycline-related cardiotoxicity.

Patients who received anthracycline-based chemotherapy between 2014 and 2018 and had baseline abdominal CT and baseline and follow-up echocardiography after anthracycline treatment were included. European Society of Cardiology ejection fraction criteria and American Society of Echocardiography diastolic dysfunction criteria were used for definition of cardiotoxicity. Sarcopenia was defined on the basis of skeletal muscle index (SMI) and psoas muscle index (PMI) calculated on CT images at L3 and L4 vertebra levels.

A total of 166 patients (75 men and 91 women) were included. Sarcopenia was determined in 33 patients (19.9%) according to L3-SMI, in 17 patients (10.2%) according to L4-SMI and in 45 patients (27.1%) according to PMI. 27 patients (16.3%) developed cardiotoxicity. PMI and L3-SMI were significantly associated with an increased risk of cardiotoxicity (L3-SMI: HR=3.27, 95% CI 1.32 to 8.11, p=0.01; PMI: HR=3.71, 95% CI 1.58 to 8.73, p=0.003).

This is the first study demonstrating a significant association between CT-diagnosed sarcopenia and anthracycline-related cardiotoxicity. Routine CT scans performed for cancer staging may help clinicians identify high-risk patients in whom closer follow-up or cardioprotective measures should be considered.

Breast cancer patients undergoing trastuzumab therapy have greater risk of cardiovascular disease. Risk factors for this effect have been proposed. However, the role of dyslipidemia is not completely understood. This systematic review aimed to explore the role of dyslipidemia in trastuzumab-induced cardiotoxicity.

The investigators searched MEDLINE, Scopus, and Web of Science up to October 25, 2020. A random-effects model was used to determine pooled estimates of the results. The primary endpoint was trastuzumab-induced cardiotoxicity in patients with and without dyslipidemia.

A total of 39 studies were selected for inclusion in our systematic review assessing 21079 patients. One study demonstrated a statistically significant association between dyslipidemia and cardiotoxicity (OR=2.28, 95% CI 1.22-4.26, p=0.01). In all other studies, no such association was observed. Twenty-one studies including 6135 patients were eligible for meta-analysis. In this meta-analysis of unadjusted data, dyslipidemia was significantly associated with cardiotoxicity (OR=1.25, 95% CI 1.01-1.53, p=0.04, I2=0%), however, a subgroup analysis of studies reporting adjusted measures did not demonstrate a significant association (OR=0.89, 95% CI 0.73-1.10, p=0.28, I2=0%).

This systematic review and meta-analysis did not demonstrate a significant association between dyslipidemia alone and the development of cardiotoxicity. In the absence of other relevant cardiovascular risk factors, review of lipid profile may not be obligatory, and management of patients could be performed without referral for cardio-oncology assessment. Further investigation of risk factors for trastuzumab-induced cardiotoxicity is required to confirm these results.

Cancer therapy-related cardiac dysfunction (CTRCD) is an important treatment-limiting toxicity for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer that adversely affects cancer and cardiovascular outcomes. Easy-to-use tools that incorporate readily accessible clinical variables for individual estimation of CTRCD risk are needed.

From 2004 to 2013, 1440 patients with stage I to III HER2-positive breast cancer treated with trastuzumab-based therapy were identified. A multivariable Cox proportional hazards model was constructed to identify risk factors for CTRCD and included the 1377 patients in whom data were complete. Nine clinical variables, including age, race, body mass index, left ventricular ejection fraction, systolic blood pressure, coronary artery disease, diabetes, arrhythmia, and anthracycline exposure were built into a nomogram estimating risk of CTRCD at 1 year. The nomogram was validated for calibration and discrimination using bootstrap resampling. A total of 177 CTRCD events occurred within 1 year of HER2-targeted treatment. The nomogram for prediction of 1-year CTRCD probability demonstrated good discrimination, with a concordance index of 0.687. The predicted and observed probabilities of CTRCD were similar, demonstrating good model calibration.

A nomogram composed of 9 readily accessible clinical variables provides an individualized 1-year risk estimate of CTRCD among women with HER2-positive breast cancer receiving HER2-targeted therapy. This nomogram represents a simple-to-use tool for clinicians and patients that can inform clinical decision-making on breast cancer treatment options, optimal frequency of cardiac surveillance, and role of cardioprotective strategies.

 Doxorubicin is an important antineoplastic agent with wide interindividual variability in response to treatment and in its cardiotoxic effects. To determine the effect of genotypic status of three single-nucleotide variants in ABCC1, NCF4, and CBR3 genes and nutritional status assessed by body mass index, on the population pharmacokinetics of Doxorubicin and its cardiotoxic effects in pediatric patients with leukemia.

Seventy pediatric patients treated with Doxorubicin were studied, in which 189 biological samples were obtained to determine Doxorubicin concentrations (1 to 3 samples per patient) at different times, for 20 h.

Low body mass index and age ≤ 7 years were associated with decreased clearance of Doxorubicin, and female gender was associated with increased clearance of Doxorubicin. Low BMI and low height were associated with a decrease and increase, respectively, in the intercompartmental clearance (Q) of Doxorubicin. TT homozygosity of the single-nucleotide variant rs3743527 of the ABCC1 gene was associated with an increase in clearance and decreased area under the curve, AA homozygosity of the single-nucleotide variant rs1883112 of the NCF4 gene was associated with a decrease in the volume of distribution in the peripheral compartment (V2), and GG homozygosity of CBR3 rs1056892 with increasing area under the curve.

Some covariates studied are directly related to the increase or decrease of the pharmacokinetic parameters of Doxorubicin. Decreased clearance, V2, and increased area under the curve were associated with systolic dysfunction, and decreased Q and V2 were associated with diastolic dysfunction. These results may contribute to the effective and safe use of Doxorubicin in pediatric patients with leukemia.

Breast cancer has become the most common cancer in the US and worldwide. While advances in early detection and treatment have resulted in a 40% reduction in breast cancer mortality, this reduction has not been achieved uniformly among racial groups. A large percentage of non-metastatic breast cancer mortality is related to the cardiovascular effects of breast cancer therapies. These effects appear to be more prevalent among patients from historically marginalized racial/ethnic backgrounds, such as African American and Hispanic individuals. Anthracyclines, particularly doxorubicin and daunorubicin, are the first-line treatments for breast cancer patients. However, their use is limited by their dose-dependent and cumulative cardiotoxicity, manifested by cardiomyopathy, ischemic heart disease, arrhythmias, hypertension, thromboembolic disorders, and heart failure. Cardiotoxicity risk factors, such as genetic predisposition and preexisting obesity, diabetes, hypertension, and heart diseases, are more prevalent in racial/ethnic minorities and undoubtedly contribute to the risk. Yet, beyond these risk factors, racial/ethnic minorities also face unique challenges that contribute to disparities in the emerging field of cardio-oncology, including socioeconomic factors, food insecurity, and the inability to access healthcare providers, among others. The current review will address genetic, clinical, and social determinants that potentially contribute to this disparity.

Cancer therapy-related cardiac dysfunction (CTRCD) is a potentially serious cardiotoxicity of treatments for ERBB2-positive breast cancer (formerly HER2). Identifying early biomarkers of cardiotoxicity could facilitate an individualized approach to cardiac surveillance and early pharmacologic intervention. Circulating cell-free DNA (cfDNA) of cardiomyocyte origin is present during acute cardiac injury but has not been established as a biomarker of CTRCD.

To determine whether circulating cardiomyocyte cfDNA is associated with CTRCD in patients with ERBB2-positive breast cancer treated with anthracyclines and ERBB2-targeted therapy.

A prospective cohort of 80 patients with ERBB2-positive breast cancer enrolled at an academic cancer center between July 2014 and April 2016 underwent echocardiography and blood collection at baseline, after receiving anthracyclines, and at 3 months and 6 months of ERBB2-targeted therapy. Participants were treated with doxorubicin-based chemotherapy followed by trastuzumab (+/- pertuzumab). The current biomarker study includes participants with sufficient biospecimen available for analysis after anthracycline therapy. Circulating cardiomyocyte-specific cfDNA was quantified by a methylation-specific droplet digital polymerase chain reaction assay. Data for this biomarker study were collected and analyzed from June 2021 through April 2022.

The outcome of interest was 1-year CTRCD, defined by symptomatic heart failure or an asymptomatic decline in left ventricular ejection fraction (≥10% from baseline to less than lower limit of normal or ≥16%). Values for cardiomyocyte cfDNA and high-sensitivity cardiac troponin I (hs-cTnI) measured after patients completed treatment with anthracyclines were compared between patients who later developed CTRCD vs patients who did not using the Wilcoxon rank sum test, and the association of post-anthracycline cardiomyocyte cfDNA level with CTRCD was estimated using logistic regression.

Of 71 patients included in this study, median (IQR) age was 50 (44-58) years, all were treated with dose-dense doxorubicin, and 48 patients underwent breast radiotherapy. Ten of 71 patients (14%) in this analysis developed CTRCD. The level of cardiomyocyte cfDNA at the post-anthracycline time point was higher in patients who subsequently developed CTRCD (median, 30.5 copies/mL; IQR, 24-46) than those who did not (median, 7 copies/mL; IQR, 2-22; P = .004). Higher cardiomyocyte cfDNA level after completion of anthracycline chemotherapy was associated with risk of CTRCD (hazard ratio, 1.02 per 1-copy/mL increase; 95% CI, 1.00-1.03; P = .046).

This study found that higher cardiomyocyte cfDNA level after completion of anthracycline chemotherapy was associated with risk of CTRCD. Cardiomyocyte cfDNA quantification shows promise as a predictive biomarker to refine risk stratification for CTRCD among patients with breast cancer receiving cardiotoxic cancer therapy, and its use warrants further validation.

ClinicalTrials.gov Identifier: NCT02177175.

Trastuzumab (Tra), the first humanized monoclonal antibody that targets human epidermal growth factor receptor 2 (HER2), is commonly used alongside doxorubicin (Dox) as a combination therapy in HER2-positive breast cancer. Unfortunately, this leads to a more severe cardiotoxicity than Dox alone. NLRP3 inflammasome is known to be involved in Dox-induced cardiotoxicity and multiple cardiovascular diseases. However, whether the NLRP3 inflammasome contributes to the synergistic cardiotoxicity of Tra has not been elucidated. In this study, primary neonatal rat cardiomyocyte (PNRC), H9c2 cells and mice were treated with Dox (15 mg/kg in mice or 1μM in cardiomyocyte) or Tra (15.75 mg/kg in mice or 1μM in cardiomyocyte), or Dox combined Tra as cardiotoxicity models to investigate this question. Our results demonstrated that Tra significantly potentiated Dox-induced cardiomyocyte apoptosis and cardiac dysfunction. These were accompanied by the increased expressions of NLRP3 inflammasome components (NLRP3, ASC and cleaved caspase-1), the secretion of IL-β and the pronounced production of ROS. Inhibiting the activation of NLRP3 inflammasome by NLRP3 silencing significantly reduced cell apoptosis and ROS production in Dox combined Tra-treated PNRC. Compared with the wild type mice, the systolic dysfunction, myocardial hypertrophy, cardiomyocyte apoptosis and oxidative stress induced by Dox combined Tra were alleviated in NLRP3 gene knockout mice. Our data revealed that the co-activation of NLRP3 inflammasome by Tra promoted the inflammation, oxidative stress and cardiomyocytes apoptosis in Dox combined Tra-induced cardiotoxicity model both in vivo and in vitro. Our results suggest that NLRP3 inhibition is a promising cardioprotective strategy in Dox/Tra combination therapy.

Aging breast cancer survivors may be at an elevated risk of cardiovascular disease (CVD), but little is known about CVD risk assessment and breast cancer in Korean women. We hypothesized that Korean breast cancer survivors would have higher risks of future CVD within the next 10 years (i.e., Framingham Risk Score [FRS]) than women without cancer.

(1) To compare FRS-based CVD risks in women with and without breast cancer based on propensity score matching; and (2) To explore adiposity-related measures in relation to FRS in Korean women with breast cancer.

Using the cross-sectional data from the 2014-2018 Korean National Health and National Survey (KNHANES), we identified 136 women with breast cancer aged 30-74 years who had no other cancer and no CVD. The comparison group of 544 women with no cancer were selected by 1:4 nearest-neighbor propensity score matching based on breast cancer diagnosis. CVD risk was assessed by FRS based on multiple traditional risk factors (e.g., cholesterol, blood pressure, diabetes, and smoking). Adiposity was measured by physical examination, including body mass index (BMI) and waist-to-height ratio (WHtR). Physical activity and health behaviors were assessed by self-reports.

Women with breast cancer (mean age of 57 years) had similar FRS levels at a low-risk category (< 10%) to women with no cancer (4.9% vs. 5.5%). Breast cancer survivors (mean 8.5 survival years) presented at significantly lower levels of total cholesterol, BMI, and WHtR (all p values < 0.05) than their counterpart. Within the breast cancer group, WHtR ≥ 0.5 was associated with higher FRS, compared to WHtR < 0.5. FRS was not different by survival < 5 years or ≥ 5 years after breast cancer diagnosis.

FRS-based CVD risks were not different in Korean, mostly postmenopausal, women by breast cancer status. Whereas breast cancer survivors had even lower levels of lipid and adiposity measures than women without cancer, those values indicating borderline cardiometabolic risk suggest continued screening and management efforts for these aging women. Future studies are needed to examine longitudinal trajectories of CVD risk factors and CVD outcomes among Korean breast cancer survivors.

Breast cancer is associated with alterations in lipid metabolism. The treatment of breast cancer can also affect serum lipid composition. The purpose of this study was the examination of serum fatty acids (FAs) profiles in breast cancer survivors to assess if the FA levels normalize.

Serum levels of FAs were determined by gas chromatography-mass spectrometry in a group of breast cancer patients at baseline (before treatment, n = 28), at two follow-up visits at 12 months (n = 27) and 24 months (n = 19) after the breast cancer resection, and in the group of healthy controls (n = 25). Multivariate analysis was performed to assess how FA serum profile changes following treatment.

Breast cancer patients' serum FA profiles at follow-ups did not normalize to the levels of control group. The greatest differences were found for levels of branched-chain (BCFA), odd-chain (OCFA) and polyunsaturated (PUFAs) FAs, all of which were significantly increased 12 months after the surgery.

After treatment for breast cancer, the patients' serum FA profile differs from the profile before treatment and from controls, especially 12 months after treatment. Some changes may be beneficial - increased BCFA and OCFA levels, and improved n-6/n-3 PUFA ratio. This may reflect lifestyle changes in breast cancer survivors and have an impact on the risk of recurrence.

Obesity is defined as a body mass index (BMI) of 30 kg/m2 or more and is associated with worse outcomes in patients with breast cancer, resulting in an increased incidence of breast cancer, recurrence, and death. The incidence of obesity is increasing, with almost half of all individuals in the United States classified as obese. Patients with obesity present with unique pharmacokinetics and physiology and are at increased risk of developing diabetes mellitus and cardiovascular disease, which leads to specific challenges when treating these patients. The aim of this review is to summarize the impact of obesity on the efficacy and toxicity of systemic therapies used for breast cancer patients, describe the molecular mechanisms through which obesity can affect systemic therapies, outline the existing American Society of Clinical Oncology (ASCO) guidelines for treating patients with cancer and obesity, and highlight additional clinical considerations for treating patients with obesity and breast cancer. We conclude that further research on the biological mechanisms underlying the obesity-breast cancer link may offer new treatment strategies, and clinicals trials that focus on the treatment and outcomes of patients with obesity and all stages of breast cancer are needed to inform future treatment guidelines.

Human epidermal growth factor receptor two (HER2) target therapies have drastically revolutionised the treatment of HER2-positive breast cancer. Starting with trastuzumab, early phase III trials have already highlighted its significant cardiotoxicity, which is also present, albeit to a lesser extent, in the new generation drugs. Also given the growing population of patients with cardiovascular diseases, it is vital to set up proper long-term follow-up to prevent morbidity related to the development of cardiotoxicity.

This review discusses the mechanisms of action underlying the cardiotoxicity of HER2 targeted therapies and the main clinical evidence on the toxicity of these drugs. In addition, the patterns of patient assessment prior to the initiation of therapy with HER2 targeted therapies are discussed, as well as the main evidence concerning the follow-up and management of cardiotoxicity.

the mechanisms of cardiotoxicity of new HER2 drugs need further study and, likewise, methods to prevent, monitor and identify HER-2-induced cardiotoxicity need to be implemented. Although some studies highlight the validity of cardiac biomarkers as predictive factors for cardiotoxicity, their actual usefulness and timing is still debated. Further studies are needed to assess the effectiveness of possible pharmacological primary prevention.

The long-term risk of incident atherosclerotic cardiovascular diseases (ASCVD) among cancer patients remains incompletely defined. This study aimed to evaluate the long-term ASCVD risk in cancer patients compared with the non-cancer population.

This was a prospective population-based study using data from the Kailuan cohort, 6,204 individuals with newly diagnosed cancer, free of ASCVD, were matched in a 1:1 ratio to non-cancer controls for age (±1) and sex, from June 2006 to December 2020. Multivariable competing risk analyses were performed to evaluate the association between cancer diagnosis and risk of incident ASCVD events (including myocardial infarction, ischemic stroke, heart failure, and revascularization with coronary artery bypass graft surgery or percutaneous coronary intervention).

During a median follow-up of 5.3 (1.7, 9.7) years, 1,019 incident ASCVD events were observed. Compared to participants without cancer, there was a similar risk for incident ASCVD events among cancer patients within the first few years after cancer diagnosis, and the risk declined over time. Overall, cancer patients showed lower risks of incident ASCVD compared to the non-cancer patients over the long term, with a hazard ratio (95% confidence interval) of 0.52 (0.45-0.60) for composite ASCVD events, 0.43 (0.35-0.53) for ischemic stroke, 0.63 (0.42-0.95) for myocardial infarction, 0.63 (0.48-0.83) for heart failure, and 0.82 (0.60-1.11) for coronary revascularization. Baseline level of low-density lipoprotein cholesterol, fasting blood glucose, blood pressure, and high-sensitivity C-reactive protein could independently predict the incident ASCVD among the study population. Subgroup analyses according to cancer types revealed a significantly lower risk of ASCVD events among patients with digestive cancer or respiratory cancer compared with non-cancer controls, but not for urologic or genital cancer. Multiple sensitivity analyses yielded similar results to the primary analysis.

Long-term ASCVD risk among cancer survivors is not increased compared with the non-cancer individuals, probably driven by a favorable profile of baseline risk factor in cancer population.

Trastuzumab and trastuzumab emtansine are specific antibody and antibody-drug conjugates used in the treatment of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. The aim of this study was to test their effect on the QTc interval duration and left ventricular ejection fraction (LVEF) in our patients, two parameters used in evaluation of cardiotoxicity. From May 2015 to October 2017, 26 patients with preserved LVEF were included in the study. All of them were previously treated with standard paclitaxel and cisplatin-based chemotherapy regimens. Electrocardiogram (ECG) was recorded just before each trastuzumab dose application and six months after the last dose. Echocardiography with LVEF measurement was performed several days before the application of the initial dose, and six months after the last cycle. Later, 24 patients with metastatic disease received additional treatment with trastuzumab emtansine after six months and the same ECG and echocardiography protocol was performed again. Due to reduction in LVEF, two patients were discontinued from additional treatment.

A statistically significant QTc prolongation was found after each drug dose application, with an increase in mean QTc duration with every successive application, reaching the peak QTc values just before the fifth cycle of treatment. The QTc interval returned to its initial value six months after the last cycle (p < 0.001). These results were similar for both drugs. Mean LVEF before both treatment protocols was significantly higher compared to LVEF value after the treatment. LVEF before trastuzumab emtansine treatment was non-significantly higher than LVEF after trastuzumab treatment.

Trastuzumab and trastuzumab emtansine cardiotoxicity manifested as a significant and progressive QTc prolongation after successive drug applications, reaching the peak value just before the fifth cycle of both drugs. Both medications also caused statistically significant but asymptomatic LVEF reduction. Complete reversibility of cardiotoxic effects of both drugs was confirmed by QTc interval and LVEF normalisation after the treatment discontinuation.

Cardiotoxicity is a serious adverse effect that can occur in women undergoing treatment for breast cancer. Identifying patients who will develop cardiotoxicity remains challenging.

To identify, describe, and evaluate all prognostic models developed to predict cardiotoxicity following treatment in women with breast cancer.

This systematic review searched the Medline, Embase, and Cochrane databases up to September 22, 2021, to include studies developing or validating a prediction model for cardiotoxicity in women with breast cancer. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to assess both the risk of bias and the applicability of the prediction modeling studies. Transparency reporting was assessed with the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) tool.

After screening 590 publications, we identified 7 prognostic model studies for this review. Six were model development studies and 1 was an external validation study. Outcomes included occurrence of cardiac dysfunction (echocardiographic parameters), heart failure, and composite clinical outcomes. Model discrimination, measured by the area under receiver operating curves or C statistic, ranged from 0.70 (95% IC, 0.62-0.77) to 0.87 (95% IC, 0.77-0.96). The most common predictors identified in final prediction models included age, baseline left ventricular ejection fraction, hypertension, and diabetes. Four of the developed models were deemed to be at high risk of bias due to analysis concerns, particularly for sample size, handling of missing data, and not presenting appropriate performance statistics. None of the included studies examined the clinical utility of the developed model. All studies met more than 80% of the items in TRIPOD checklist.

In this systematic review of the 6 predictive models identified, only 1 had undergone external validation. Most of the studies were assessed as being at high overall risk of bias. Application of the reporting guidelines may help future research and improve the reproducibility and applicability of prediction models for cardiotoxicity following breast cancer treatment.

Framingham risk score (FRS) is an effective tool for evaluating the 10-year risk of cardiovascular diseases. However, the sensitivity of FRS for anthracycline-induced cardiotoxicity is unclear. This meta-analysis aims to evaluate the correlation between risk factors (hypertension, hyperlipidemia, diabetes, smoking, and obesity) in FRS and anthracycline-induced cardiotoxicity in breast cancer.

We searched PubMed, EMBASE, and Cochrane Library for studies published from inception to January 2022 which reported cardiotoxicity due to anthracycline. Cardiotoxicity defined as any cardiac events were used as the primary endpoint. A total of 33 studies involving 55,708 breast cancer patients treated with anthracyclines were included in this meta-analysis.

At least one risk factor was identified at baseline for the 55,708 breast cancer patients treated with anthracycline. Hypertension [I 2 = 45%, Fixed, RR (95% CI) = 1.40 (1.22, 1.60), p < 0.00001], hyperlipidemia [I 2 = 0%, Fixed, RR (95% CI): 1.35 (1.12, 1.62), p = 0.002], diabetes [I 2 = 0%, Fixed, RR (95% CI): 1.29 (1.05, 1.57), p = 0.01], and obesity [I 2 = 0%, Fixed, RR (95% CI): 1.32 (1.05, 1.67), p = 0.02] were associated with increased risks of cardiac events. In addition, smoking was also associated with reduced left ventricular ejection fraction (LVEF) during anthracycline chemotherapy [I 2 = 0%, Fixed, OR (95% CI): 1.91 (1.24, 2.95), p = 0.003] in studies that recorded only the odds ratio (OR).

Hypertension, hyperlipidemia, diabetes, smoking, and obesity are associated with increased risks of anthracycline-induced cardiotoxicity. Therefore, corresponding measures should be used to manage cardiovascular risk factors in breast cancer during and after anthracycline treatment.