The discipline of Cardio-Oncology has seen tremendous growth over the past decade. It is devoted to the cardiovascular (CV) care of the cancer patient, especially to the mitigation and management of CV complications or toxicities of cancer therapies, which can have profound implications on prognosis. To that effect, many studies have assessed CV toxicities in patients undergoing various types of cancer therapies; however, direct comparisons have proven difficult due to lack of uniformity in CV toxicity endpoints. Similarly, in clinical practice, there can be substantial differences in the understanding of what constitutes CV toxicity, which can lead to significant variation in patient management and outcomes. This document addresses these issues and provides consensus definitions for the most commonly reported CV toxicities, including cardiomyopathy/heart failure and myocarditis, vascular toxicity, and hypertension, as well as arrhythmias and QTc prolongation. The current document reflects a harmonizing review of the current landscape in CV toxicities and the definitions used to define these. This consensus effort aims to provide a structure for definitions of CV toxicity in the clinic and for future research. It will be important to link the definitions outlined herein to outcomes in clinical practice and CV endpoints in clinical trials. It should facilitate communication across various disciplines to improve clinical outcomes for cancer patients with CV diseases.

PURPOSE: APHINITY, at 45 months median follow-up, showed that pertuzumab added to adjuvant trastuzumab and chemotherapy significantly improved invasive disease–free survival (IDFS) (hazard ratio 0.81 [95% CI, 0.66 to 1.00], P = .045) for patients with early human epidermal growth factor receptor 2 (HER2)–positive breast cancer (BC), specifically those with node-positive or hormone receptor (HR)–negative disease. We now report the preplanned second interim overall survival (OS) and descriptive updated IDFS analysis with 74 months median follow-up. METHODS: After surgery and central HER2-positive confirmation, 4,805 patients with node-positive or high-risk node-negative BC were randomly assigned (1:1) to either 1-year pertuzumab or placebo added to standard adjuvant chemotherapy and 1-year trastuzumab. RESULTS: This interim OS analysis comparing pertuzumab versus placebo did not reach the P = .0012 level required for statistical significance ( P = .17, hazard ratio 0.85). Six-year OS were 95% versus 94% with 125 deaths (5.2%) versus 147 (6.1%), respectively. IDFS analysis based on 508 events (intent-to-treat population) showed a hazard ratio of 0.76 (95% CI, 0.64 to 0.91) and 6-year IDFS of 91% and 88% for pertuzumab and placebo groups, respectively. The node-positive cohort continues to derive clear IDFS benefit from pertuzumab (hazard ratio 0.72 [95% CI, 0.59 to 0.87]), 6-year IDFS being 88% and 83%, respectively. Benefit was not seen in the node-negative cohort. In a subset analysis, IDFS benefit from pertuzumab showed a hazard ratio of 0.73 (95% CI, 0.59 to 0.92) for HR-positive disease and a hazard ratio of 0.83 (95% CI, 0.63 to 1.10) for HR-negative disease. Primary cardiac events remain < 1% in both the treatment groups. No new safety signals were seen. CONCLUSION: This analysis confirms the IDFS benefit from adding pertuzumab to standard adjuvant therapy for patients with node-positive HER2-positive early BC. Longer follow-up is needed to fully assess OS benefit.

Aims: The national incidence, risk factors, and associated mortality of atrial fibrillation (AF) in breast cancer patients are unknown. Methods and results: Using the Surveillance, Epidemiology, and End Results-Medicare-linked database, we identified females, ≥66 years old, with a new primary diagnosis of breast cancer from 2007 through 2014. These patients were individually matched 1:1 to Medicare enrolees without cancer, and each pair was followed for 1 year to identify a primary outcome of AF. Cumulative incidence was calculated using competing risk survival statistics. Following this, identifying risk factors of AF among breast cancer patients was conducted using the adjusted Cox proportional hazards model. Finally, Kaplan–Meier methods and adjusted Cox proportional hazards modelling were performed to estimate mortality in breast cancer patients with incident and prevalent AF. This study included 85 423 breast cancer patients. Among these 9425 (11.0%) had AF diagnosis prior to the breast cancer diagnosis. New-onset AF was diagnosed in 2993 (3.9%) patients in a 1-year period after the breast cancer diagnosis [incidence 3.3%, 95% confidence interval (CI) 3.0–3.5%, at 1 year; higher rate in the first 60 days (0.6%/month)]. Comparatively, the incidence of new-onset AF in matched non-cancer controls was 1.8% (95% CI 1.6–2.0%). Apart from traditional demographic and cardiovascular risk factors, breast cancer stage was strongly associated with the development of AF [American Joint Committee on Cancer (AJCC) Stage II/III/IV vs. I: adjusted hazard ratio (aHR) 1.51/2.63/4.21, respectively]. New-onset AF after breast cancer diagnosis (aHR 3.00) is associated with increased 1-year cardiovascular mortality. Conclusion: AF incidence is significantly higher in women after a breast cancer diagnosis. Higher breast cancer stages at diagnos are significantly associated with a higher risk of AF. New-onset AF in the new breast cancer diagnosis setting increases 1-year cardiovascular mortality but not breast cancer-related mortality. Key Question: What are the incidence, prevalence, risk factors and mortality outcomes of atrial fibrillation (AF) in a multi-ethnic representative United States cohort of breast cancer patients? Key Finding: Annual incidence for AF is 3.9% with highest rate in the first 60 days after cancer diagnosis. Cancer stage and grade are the strongest risk factors for AF. New onset AF after breast cancer increases all-cause and cardiovascular mortality. Take Home Message: AF incidence is higher in breast cancer patients and is associated with later stage and grade at diagnosis of breast cancer. Involving cardio-oncology in those who develop AF after cancer diagnosis should be encouraged to improve their cardiovascular and overall prognosis.

Background: Cyclin‐dependent kinase (CDK) 4 and 6 inhibitors have significantly improved survival in patients with hormone receptor–positive metastatic breast cancer. There are few data regarding the epidemiology of cardiovascular adverse events (CVAEs) with these therapies. Methods and Results: Using the OneFlorida Data Trust, adult patients without prior cardiovascular disease who received at least 1 CDK4/6 inhibitor were included in the analysis. CVAEs identified from International Classification of Diseases , Ninth and Tenth Revisions ( ICD‐9/10 ) codes included hypertension, atrial fibrillation(AF)/atrial flutter (AFL), heart failure/cardiomyopathy, ischemic heart disease, and pericardial disease. Competing risk analysis (Fine–Gray model) was used to determine the association between CDK4/6 inhibitor therapy and incident CVAEs. The effect of CVAEs on all‐cause death was studied using Cox proportional hazard models. Propensity‐weight analyses were performed to compare these patients to a cohort of patients treated with anthracyclines. A total of 1376 patients treated with CDK4/6 inhibitors were included in the analysis. CVAEs occurred in 24% (35.9 per 100 person‐years). CVAEs were slightly higher in patients who received CKD4/6 inhibitors compared with anthracyclines ( P =0.063), with higher death rate associated with the development of AF/AFL or cardiomyopathy/heart failure in the CDK4/6 group. The development of cardiomyopathy/heart failure and AF/AFL was associated with increased all‐cause death (adjusted hazard ratio [HR], 4.89 [95% CI, 2.98–8.05]; and 5.88 [95% CI, 3.56–9.73], respectively). Conclusions: CVAEs may be more common with CDK4/6 inhibitors than previously recognized, with increased death rates in these patients who develop AF/AFL or heart failure. Further research is needed to definitively determine cardiovascular risk associated with these novel anticancer treatments.