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Background: During the COVID pandemic, we designed and implemented a program, called BQual-D, to maintain high quality care for patients with HR+, HER2 negative MBC who were taking oral anti-cancer therapy and needed to shelter at home. This program augmented available clinical resources with (1) trained nurse coaches to manage side effects, improve adherence, monitor for cancer progression and screen for psychological distress via telehealth, and (2) a care coordinator to arrange blood testing at local labs to facilitate timely medication dose adjustments. BQual-D served patients from August, 2020 through April of 2021. Here, we describe survey results assessing provider satisfaction with BQual-D. Methods: Surveys assessing provider satisfaction were distributed in December, 2020 (Survey#1) and in April, 2021 (Survey#2). Provider demographics were collected with Survey#1. Eight questions assessed satisfaction with different aspects of the BQual-D program, including content of the nurse coach notes, communication with the program, timeliness of communication, frequency of notes, ease of reading the notes, ease of referring patients, and turnaround time for labs, which were rated on a Likert scale of 1 (strongly dissatisfied) to 10 (strongly satisfied), with an additional response choice of 0 (unable to assess). Providers were also asked if BQual-D led to changes in patient management (yes/no), the degree to which BQual-D supported the medical management of the patient (from 1=not at all to 7=significantly), the influence of BQual-D on patient wellbeing (positive effects, no change, negative effects), and the overall quality of care delivered by the program (from 1=excellent to 4=poor). Finally, we asked providers if they would continue to recommend their patients to BQual-D (yes, in the same way as the program has been deployed; yes but with improvements; or no). Results are described by frequencies and means. Results: Nineteen providers responded to Survey#1. Providers were physicians (31.6%), advanced practice providers (31.6%), nurses (31.6%) and a clinical pharmacist (5.3%). Respondents were 89.5% female, 94.7% White, and had a mean age of 44 years and mean 11 years in practice. Providers rated the quality of care provided by the BQual-D program as excellent (44%) or good (57%), all providers surveyed indicated that they would continue to recommend the program to patients, and 95% of providers indicated that the program had a positive effect on patients’ well-being. Half of the respondents indicated that BQual-D resulted in changes in or addition to patient management and 90% indicated that BQual-D significantly supported medical management. Providers were strongly satisfied (scores of 8-10 on the Likert scale) with overall communication with the BQual-D team (74%) and timeliness of communications (79%). Providers were also strongly satisfied with the content (68.4%), frequency (74%), and ease of reading (68%) program notes. Seven providers completed Survey#2, in which providers rated the overall quality of the program as excellent (57%) or good (43%); 86% indicated that they would continue to recommend the program to patients, and 86% indicated that the program had a positive effect on patients’ well-being. Conclusions: During the COVID pandemic, when sheltering at home was encouraged, provider satisfaction with BQual-D, which provided additional health resources (nurse coaches, care coordinator) to support patients on oral therapy for HR+ MBC, was high. Resources needed to implement BQual-D should be explored as a way of providing additional support for patients and providers in order to minimize the requirement for in-person visits. Funding: Supported by a grant from Pfizer. Citation Format: Gretchen Kimmick, Smrithi Davakaran, Heather Moore, Cynthia Rose, Pamela Gentry, Michael Willis, Susan Dent, Sarah Sammons, Jeremy Force, Kelly Westbrook, Carey Anders, Rebecca Shelby. Best quality care from a distance (BQual-D): Maintaining high quality care for hormone receptor positive (HR+) metastatic breast cancer (MBC) during the COVID pandemic, description of the program and provider satisfaction [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-06.

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.

Cancer patients and survivors have elevated cardiovascular risk when compared with noncancer patients. Cardio-oncology has emerged as a new subspecialty to comanage and address cardiovascular complications in cancer patients such as heart failure, atherosclerotic cardiovascular disease (ASCVD), valvular heart disease, pericardial disease, and arrhythmias. Cardiac computed tomography (CT) can be helpful in identifying both clinical and subclinical ASCVD in cancer patients and survivors. Radiation therapy treatment planning CT scans and cancer staging/re-staging imaging studies can quantify calcium scores which can identify pre-existing subclinical ASCVD. Cardiac CT can be helpful in the evaluation of cardiac tumors and pericardial diseases, especially in patients who cannot tolerate or have a contraindication to cardiac magnetic resonance. In this review, we describe the optimal utilization of cardiac CT in cancer patients, including risk assessment for ASCVD and identification of cancer treatment-related cardiovascular toxicity., Central Illustration, Highlights • Cardiac CT can assess for subclinical atherosclerosis, allowing for better risk stratification. • Cardiac CT has high accuracy to evaluate for obstructive coronary artery disease. • CAC scanning may be useful after radiation therapy to assess the extent of vascular calcifications. • Cardiac CT can accurately depict cardiac tumors, pericardial effusions, and cardiac function.

Contemporary anticancer drugs have significantly improved cancer survival at the expense of cardiovascular toxicities, including heart disease, thromboembolic disease, and hypertension. One of the most common side effects of these drugs is hypertension, especially in patients treated with vascular endothelial growth factor inhibitors, as well as tyrosine kinase inhibitors and proteasome inhibitors. Adjunctive therapy, including corticosteroids, calcineurin inhibitors, and nonsteroidal anti-inflammatories, as well as anti-androgen hormone therapy for prostate cancer, may further increase blood pressure in these patients. Cancer therapy-induced hypertension is often dose limiting, increases cardiovascular mortality in cancer survivors, and is usually reversible after interruption or discontinuation of treatment. The exact molecular mechanisms underlying hypertension are unclear, but recent discoveries indicate an important role for reduced nitric oxide generation, oxidative stress, endothelin-1, prostaglandins, endothelial dysfunction, increased sympathetic outflow, and microvascular rarefaction. In addition, genetic polymorphisms in vascular endothelial growth factor receptors are implicated in vascular endothelial growth factor inhibitor-induced hypertension. Diagnosis, management, and follow-up of cancer therapy-induced hypertension follow national hypertension guidelines because evidence-based clinical trials specifically addressing patients who develop hypertension as a result of cancer therapy are currently lacking. Rigorous baseline assessment of patients before therapy is started requires particular emphasis on assessing and treating cardiovascular risk factors. Hypertension management follows guidelines for the general population, although special attention should be given to rebound hypotension after termination of cancer therapy. Management of these complex patients requires collaborative care involving oncologists, cardiologists, hypertension specialists, primary care professionals, and pharmacists to ensure the optimal therapeutic effect from cancer treatment while minimizing competing cardiovascular toxicities.

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: Human epidermal growth factor receptor 2 (HER2) overexpressing malignancies, including breast and gastro-esophageal, are associated with a poor prognosis. The cardiotoxicity of trastuzumab, a HER2-targeting monoclonal antibody, is well established. However, the cardiotoxic effect of pertuzumab, another HER2-directed therapy, is less well documented. The objective of this systematic review and meta-analysis was to determine the risk of cardiac events in patients with HER2-positive cancer who are receiving pertuzumab. Methods: We performed a systematic review of phase 2 and 3 randomized controlled trials in which the addition of pertuzumab to other standard therapies in patients with stage I-IV HER2-positive cancer was evaluated, and cardiac adverse effects reported. We searched MEDLINE (1946-2020), Embase (1974-2020), and CENTRAL. Two independent reviewers assessed the risk of bias and extracted the data. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated from the pooled data using the inverse variance method and random-effects models. Results: Eight randomized controlled trials (8420 patients) were included: 1 was gastro-esophageal; 7 were breast cancer trials. Participants’ median age ranged from 49 to 61.5 years. All participants received trastuzumab and chemotherapy in addition to pertuzumab or placebo. Compared with placebo, pertuzumab increased the risk of clinical heart failure (HF; RR [95% CI]: 1.97 [1.05-3.70]; I2 = 0%). However, pertuzumab had no demonstrable effect on asymptomatic/minimally symptomatic left ventricular systolic dysfunction (RR [95% CI]: 1.19 [0.89-1.61]; I2 = 19%). Conclusions: Pertuzumab increases the risk of clinical HF, but not asymptomatic/minimally symptomatic left ventricular systolic dysfunction, in HER2-positive cancer patients. Further research into the mechanisms underlying pertuzumab-related HF is needed to understand its clinical spectrum of cardiotoxicity. Résumé: Introduction: Les tumeurs malignes qui surexpriment le récepteur 2 du facteur de croissance épidermique humain (HER2, de l’anglais Human epidermal growth factor receptor 2), notamment le cancer du sein et le cancer de la jonction gastro-œsophagienne, sont associées à un mauvais pronostic. La cardiotoxicité du trastuzumab, un anticorps monoclonal qui vise le HER2, est bien établie. Toutefois, les effets cardiotoxiques du pertuzumab, un autre traitement qui vise le HER2, sont moins bien démontrés. L’objectif de cette revue systématique et de cette méta-analyse était de déterminer le risque d’événements cardiaques chez les patients atteints d’un cancer HER2 positif qui prennent du pertuzumab. Méthodes: Nous avons réalisé une revue systématique d’essais comparatifs à répartition aléatoire de phase 2 et de phase 3 lors desquels nous avons évalué l’ajout du pertuzumab à d’autres traitements standards chez les patients atteints d’un cancer HER2 positif de stades I-IV, et signalé les effets indésirables sur le cœur. Nous avons fait des recherches dans MEDLINE (1946-2020), Embase (1974-2020) et CENTRAL. Deux examinateurs indépendants ont évalué le risque de biais et extrait les données. Les données groupées ont permis de calculer les intervalles de confiance (IC) à 95 % des risques relatifs (RR) au moyen de la méthode de la variance inverse et des modèles à effets aléatoires. Résultats: Nous avons inclus huit essais contrôlés randomisés (8420 patients), soit un qui portait sur le cancer de la jonction gastro-œsophagienne, et sept sur le cancer du sein. L’âge médian des participants se situait entre 49 à 61,5 ans. Tous les participants ont pris le trastuzumab et ont suivi une chimiothérapie en plus de la prise du pertuzumab ou du placebo. Comparativement au placebo, le pertuzumab a fait augmenter le risque de manifestations cliniques de l’insuffisance cardiaque (IC) (RR [IC à 95 %] : 1,97 [1,05-3,70]; I2 = 0 %). Toutefois, le pertuzumab n’a démontré aucun effet sur la dysfonction systolique du ventricule gauche asymptomatique/minimalement symptomatique (RR [IC à 95 %] : 1,19 [0,89-1,61]; I2 = 19 %). Conclusions: Le pertuzumab fait augmenter le risque de manifestations cliniques de l’IC, mais pais la dysfonction systolique du ventricule gauche asymptomatique/minimalement symptomatique, chez les patients atteints d’un cancer HER2 positif. Des recherches plus approfondies sur les mécanismes sous-jacents à l’IC liée au pertuzumab sont nécessaires pour comprendre son spectre de manifestations cliniques de cardiotoxicité.

With the aim of improving personalized treatment of patients on chemotherapy, the objective of the study was to assess the degree of association between selected Quality of life (QoL) indicators and both clinical and imaging cardiac status indicators when detecting deterioration in QoL of these patients.In a cohort clinical study in Hamburg, from August 2017 through October 2020, 59 cancer patients, aged 18-80 years, were evaluated before chemotherapy, and at several follow-ups, using EQ-5D and SF-36 QoL questionnaires, fast strain-encoded (fast-SENC) cardiac magnetic resonance (CMR), conventional CMR, and echocardiography, and further received a clinical and biomarker examination. Data was analyzed using survival analyses. A decline of more than 5% in each observed QoL metric value was defined as the observed event. Patient were separated into groups according to the presentation of cardiotoxicity as per its clinical definition, the establishment of the indication for cardioprotective therapy initiation, and by a worsening in the value of each observed imaging metric by more than 5% in the previous follow-up compared to the corresponding pre-chemotherapy baseline value.Among clinical cardiac status indicators, the indication for cardioprotective therapy showed statistically good association with QoL scores (EQ-5D p=0.028; SF-36 physical component p=0.016; SF-36 mental component p=0.012). In terms of imaging metrics, the MyoHealth segmental myocardial strain score was the only one demonstrating consistently good QoL score association (EQ-5D p=0.005; SF-36 physical component p=0.056; SF-36 mental component p=0.002).Established fast-SENC CMR scores are capable of highlighting patients with reduced QoL, who require more frequent/optimal management.Z namenom izboljšati personalizirano zdravljenje bolnikov, ki prejemajo kemoterapijo, je bil cilj naše raziskave oceniti stopnjo povezanosti med izbranimi kazalniki kakovosti življenja (QoL) ter kliničnimi in slikovnimi kazalniki srčnega statusa v kontekstu zaznave poslabšanja QoL teh bolnikov.V kohortni klinični študiji v Hamburgu smo od avgusta 2017 do oktobra 2020 59 bolnikom z rakom, starim 18–80 let, pred kemoterapijo in več kontrolnimi pregledi, napravili oceno QoL z vprašalnikoma EQ-5D in SF-36, hitro z deformacijo miokarda kodirano (fast-SENC) magnetnoresonančno slikanje srca (CMR), konvencionalno CMR, ultrazvočni pregled srca ter klinični pregled z določitvijo biomarkerjev. Podatke smo analizirali z analizo preživetja. Upad za več kot 5 % v vrednosti posameznega opazovanega kazalnika QoL je bil izbran kot opazovani dogodek. Razdelitev bolnikov v skupine je bila definirana glede na pojav kardiotoksičnosti po njeni klinični definiciji, postavitev indikacije za zdravljenje z zdravili za zaščito srčne mišice ter na osnovi poslabšanja vrednosti posameznega opazovanega slikovnega kazalnika za več kot 5 % ob zadnjem kontrolnem pregledu v primerjavi z njegovo vrednostjo pred pričetkom kemoterapije.Med kliničnimi kazalniki srčnega statusa je postavitev indikacije za zdravljenje z zdravili za zaščito srčne mišice pokazala statistično dobro povezanost s kazalniki QoL (EQ-5Dp = 0,028; SF-36 telesna komponenta p = 0,016; SF-36 mentalna komponenta p = 0,012). Med slikovnimi kazalniki je bila MyoHealth ocena segmentne krčljivosti miokarda edina, ki je pokazala konsistentno dobro povezanost s kazalniki QoL (EQ-5D p = 0,005; SF-36 telesna komponenta p = 0,056; SF-36 mentalna komponenta p = 0,002).Uveljavljeni fast-SENC kazalniki CMR so se pokazali za sposobne izpostaviti bolnike z zmanjšano QoL, ki potrebujejo pogostejšo/optimalnejšo obravnavo.

Precision medicine has ushered in a new era of targeted treatments for numerous malignancies, leading to improvements in overall survival. Unlike traditional chemotherapy, many molecular targeted antineoplastic agents are available in oral formulation, leading to enhanced patient convenience and a perception of reduced risk of adverse effects. Although oral antineoplastic agents are generally well-tolerated, cardiovascular toxicities are being reported with increasing frequency in part due to U.S. Food and Drug Administration and manufacturer recommended cardiac monitoring. Monitoring strategies have focused on left ventricular dysfunction, hypertension, and QT prolongation/arrhythmias. Given the rapid pace of development and availability of new oral antineoplastic agents, the purpose of this review is to provide clinicians with an up-to-date practical approach to monitoring and management of cardiovascular toxicities with the aim of improving overall outcomes for patients with cancer.

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.

The field of cardio-oncology was born from the necessity for recognition and management of cardiovascular diseases among patients with cancer. This need for this specialty continues to grow as patients with cancer live longer as a result of lifesaving targeted and immunologic cancer therapies beyond the usual chemotherapy and/or radiation therapy. Often, potentially cardiotoxic anticancer treatment is necessary in patients with baseline cardiovascular disease. Moreover, patients may need to continue therapy in the setting of incident cancer therapy-associated cardiotoxicity. Herein, we present and discuss the concept of

Background: CDK 4/6 inhibitors in patients (pts) with HR+/HER2- ABC has led to significant improvements in clinical outcomes, however our understanding of the impact of these treatments on CV health is unknown. Gains in overall survival should not be offset by increased CV morbidity and mortality; a particular concern given the shared risk factors for both breast cancer and CV disease. Objective: The aim of this study was to describe patient characteristics, treatment patterns and cardiovascular risk factors and disease in pts with ABC treated with endocrine therapy (ET) or ET + CDK 4/6 inhibitor. Methods: We retrospectively studied pts with HR+/HER2- ABC who were receiving first line endocrine therapy. Post-menopausal (PM) women, pre-menopausal women on ovarian suppression (OS), and men were included. Two cohorts were included: Group A - treated with ET alone (2012-2014; prior to US approval of CDK 4/6 inhibitors) and Group B - treated with ET+ CDK 4/6 inhibitor (2015-2017). The following data was extracted from Duke University Health System’s electronic medical record (EPIC) and entered into a REDCap database: demographics, baseline cardiovascular risk factors, and co-morbidities. Pt characteristics are summarized using medians and interquartile ranges for continuous variables and categorical descriptions are summarized using frequencies and percentages. Results: In total 103 patients were included with 57 in Group A (ET alone) and 46 in Group B (ET + CDK 4/6 inhibitor). Median age was 62.0 and 63.5 years in Group A and B, respectively. Fifty-three (93%) of pts in Group A were PM women compared to 37 (80%) PM women and 1 (3%) male in Group B. The groups seemed to be similar in terms of race (white 70% vs 72%), baseline body mass index (28.2 vs 27.6), baseline systolic blood pressure (132.0 vs 135.5) and diastolic blood pressure (79.0 vs 77.5). Similarly, the groups seemed to be similar in baseline hypertension (68% vs 62%); diabetes (23% vs 24%); Hemoglobin A1c (7.2% vs 6.4%) or family history of CV disease (56% vs 55%), Group A versus Group B, respectively. There were slightly more current/past smokers in Group B than Group A (48% vs 35%) and more pts in Group A with a history of hyperlipidemia relative to Group B (52% vs 31%). Conclusions: In this retrospective descriptive cohort study there seemed to be no differences in demographics or baseline CV risk factors between the ET and ET + CDK 4/6 inhibitor cohorts with the exception of more baseline hyperlipidemia in the ET cohort. This might suggest that baseline CV risk factors did not dissuade practioners from prescribing ET + CDK 4/6 inhibitor therapy. We plan to expand our cohort to collect information on type and duration of ET and CDK 4/6 inhibitors, reason for treatment discontinuation, and CV events (eg heart failure, arrhythmias, stroke, myocardial infarction), to better understand the impact that cardiovascular risk factors have on outcomes in breast cancer patients taking ET+ CDk 4/6 inhibitor. Table 1: Demographics and CV risk factors in ABC patients treated with ET or ET + CDK4/6 inhibitor Median (IQR) unless otherwise indicatedGroup A ET (n=57)Group B ET+ CDK 4/6 inhibitor (n=46)Age median (range)62.0 (27-84)63.5 (30-82)Menopausal status, n (%) Post menopausal Premenopausal + OS Male53 (93) 4 (7) 037 (80) 8 (17) 1 (3)Race, n (%) White Other40 (70) 17 (30)33 (72) 13 (28)Type of Insurance, n (%) Private Medicare Medicare and Private Medicaid Medicaid and Medicare Vererans Sponsored Self-Pay Unknown19 (33) 14 (25) 16 (28) 1 (2) 4 (7) 0 3 (5) 019 (41) 4 (9) 15 (33) 1 (2) 4 (9) 1 (2) 0 2 (4)BMI (kg/m2)28.2 (24.9, 30.6)27.6 (24.4, 34.5)Baseline BP (mmHg) Systolic Diastolic132.0 (118.0, 145.0) 79.0 (73.0, 84.0)135.5 (124.0, 149.0) 77.5 (72.0, 84.0)HgbA1c (%)7.2 (6.4, 7.4)6.4 (5.4, 6.4)CVRF, n (%) Hypertension Diabetes FH CVD Current/past smokers Hyperlipidemia36 (68) 13 (23) 28 (56) 20 (35) 29 (52)28 (62) 11 (24) 22 (55) 22 (48) 14 (31)OS = ovarian suppression; BMI = body mass index; BP = blood pressure; HgbA1c = hemoglobin A1c; CVRF = cardiovascular risk factors; FH = family history; CVD = cardiovascular disease; IQR = Interquartile range Citation Format: Susan Dent, Gloria Broadwater, Terry Hyslop, Kevin Oeffinger, Michel Khouri, Sanjeev Balu, Gretchen Kimmick. Cardiovascular (CV) risk profile in patients with estrogen receptor (ER) positive HER2 negative advanced breast cancer (ABC): A retrospective cohort study (CAREB) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-48.

Background The phase III SANDPIPER study assessed taselisib (GDC-0032), a potent, selective PI3K inhibitor, plus fulvestrant in estrogen receptor-positive, HER2-negative, PIK3CA-mutant locally advanced or metastatic breast cancer. Patients and methods Postmenopausal women with disease recurrence/progression during/after an aromatase inhibitor were randomized 2 : 1 to receive taselisib (4 mg; taselisib arm) or placebo (placebo arm) plus fulvestrant (500 mg). Stratification factors were visceral disease, endocrine sensitivity, and geographic region. Patients with PIK3CA-mutant tumors (central cobas® PIK3CA Mutation Test) were randomized separately from those without detectable mutations. The primary endpoint was investigator-assessed progression-free survival (INV-PFS) in patients with PIK3CA-mutant tumors. Secondary endpoints included objective response rate, overall survival, clinical benefit rate, duration of objective response, PFS by blinded independent central review (BICR-PFS), safety, and time to deterioration in health-related quality of life. Results The PIK3CA-mutant intention-to-treat population comprised 516 patients (placebo arm: n = 176; taselisib arm: n = 340). INV-PFS was significantly improved in the taselisib {7.4 months [95% confidence interval (CI), 7.26-9.07]} versus placebo arm (5.4 months [95% CI, 3.68-7.29]) (stratified hazard ratio [HR] 0.70; 95% CI, 0.56-0.89; P = 0.0037) and confirmed by BICR-PFS (HR 0.66). Secondary endpoints, including objective response rate, clinical benefit rate, and duration of objective response, showed consistent improvements in the taselisib arm. Safety was assessed in all randomized patients who received at least one dose of taselisib/placebo or fulvestrant regardless of PIK3CA-mutation status (n = 629). Serious adverse events were lower in the placebo versus taselisib arm (8.9% versus 32.0%). There were more discontinuations (placebo arm: 2.3%; taselisib arm: 16.8%) and dose reductions (placebo arm: 2.3%; taselisib arm: 36.5%) in the taselisib arm. Conclusion SANDPIPER met its primary endpoint; however, the combination of taselisib plus fulvestrant has no clinical utility given its safety profile and modest clinical benefit.

Serum biomarkers are an important tool in the baseline risk assessment and diagnosis of cardiovascular disease in cancer patients receiving cardiotoxic cancer treatments. Increases in cardiac biomarkers including cardiac troponin and natriuretic peptides can be used to guide initiation of cardioprotective treatments for cancer patients during treatment and to monitor the response to cardioprotective treatments, and they also offer prognostic value. This position statement examines the role of cardiac biomarkers in the management of cancer patients. The Cardio-Oncology Study Group of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the Cardio-Oncology Council of the ESC have evaluated the current evidence for the role of cardiovascular biomarkers in cancer patients before, during and after cardiotoxic cancer therapies. The characteristics of the main two biomarkers troponin and natriuretic peptides are discussed, the link to the mechanisms of cardiovascular toxicity, and the evidence for their clinical use in surveillance during and after anthracycline chemotherapy, trastuzumab and HER2-targeted therapies, vascular endothelial growth factor inhibitors, proteasome inhibitors, immune checkpoint inhibitors, cyclophosphamide and radiotherapy. Novel surveillance clinical pathways integrating cardiac biomarkers for cancer patients receiving anthracycline chemotherapy or trastuzumab biomarkers are presented and future direction in cardio-oncology biomarker research is discussed.

Anthracyclines are frequently used in adjuvant treatment for early-stage breast cancer (ESBC). The purpose of this study was to evaluate cardiotoxic effects in the first five years after treatment with different anthracycline-based regimens. CCTG MA.21 (NCT000142) was a phase III trial in ESBC that compared cyclophosphamide (75 mg/m2) orally for 14 days, epirubicin (60 mg/m2) and fluorouracil, IV days one and eight (CEF) for six cycles; dose-dense epirubicin (120 mg/m2) and cyclophosphamide, IV every 2 weeks for six cycles with concurrent G-CSF then paclitaxel every 2 weeks for four cycles (ddEC/T); doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks for four cycles then four cycles q3 weekly paclitaxel (175 mg/m2) (AC/T). Endpoints: LVEF decline; LV function changes (heart failure), or Grade 3–4 cardiac ischemia/infarction. A competing risk analysis was performed with endpoints of cardiotoxicity or recurrence in first 5 years after completion of chemotherapy. 2104 women were randomized. Compliance with cardiac LVEF assessments was 70% at 5 years in all arms. The 5-year cumulative risks of any cardiac event for CEF, ddECT, and AC/T were 22.3% (95%CI 18.9 to 25.7), 14.2% (95%CI 11.0 to 17.3), and 8.1% (95%CI 5.8 to 10.4), respectively, p

This position statement from the Heart Failure Association of the European Society of Cardiology Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society presents practical, easy-to-use and evidence-based risk stratification tools for oncologists, haemato-oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi-targeted kinase inhibitors for chronic myeloid leukaemia targeting BCR-ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies.

In the cardio-oncology population, drug interactions are of particular importance given the complex pharmacological profile, narrow therapeutic index, and inherent risk of therapies used to manage cardiovascular disease and cancer. Drug interactions may be beneficial or detrimental to the desired therapeutic effect. Clinicians in both cardiology and oncology should be cognizant of these potential drug-drug interactions that may reduce the efficacy or safety of either cardiovascular or cancer therapies. These risks can be mitigated through increased recognition of potential drug-drug interaction, use of alternative medications when possible, and careful monitoring. This scientific statement provides clinicians with an overview of pharmacodynamic and pharmacokinetic drug-drug interactions in patients with cancer exposed to common cardiovascular and cancer medications.

Breast cancer treatment can have a diverse array of delayed and long-term effects, including cardiovascular events such as heart failure, valvular damage, coronary artery disease, arrythmias, and cardiac dysfunction. The adverse cardiovascular effects of anthracyclines and trastuzumab in the treatment of early and advanced breast cancer have been well elucidated withing the literature; however, there is less understanding of the potential cardiovascular impact of more recent novel breast cancer therapies. Dual HER2 targeted therapy (pertuzumab/trastuzumab) is now standard of care for neoadjuvant and adjuvant treatment, particularly in the setting of lymph node involvement, but is there a higher risk of cardiotoxicity? There is a limited understanding of the potential short- and long-term cardiovascular toxicity associated with antibody-drug conjugates, such as T-DM1 and fam-trastuzumab deruxtecan, and well as oral anti-HER2 tyrosine kinase inhibitors such as lapatinib, neratinib, and more recently tucatinib. CDK4/6 inhibitors (eg ribociclib) combined with endocrine therapy have significantly improved clinical outcomes for individuals with hormone receptor positive, HER-2 advanced breast cancer but are associated with an increased risk of QTc prolongation, which can be compounded by electrolyte abnormalities and drug-drug interactions. Immune checkpoint inhibitors (pembrolizumab) are approved in the neoadjuvant (high risk) and advanced setting (PDL-1 positive) for triple negative breast cancer but are associated with several toxicities including endocrinopathies and rarely fatal myocarditis. The goal of this session is to improve the awareness and understanding of the potential cardiovascular toxicities associated with modern anti-cancer therapies used in the treatment of breast cancer. Citation Format: Susan Dent. Beyond anthracyclines and trastuzumab: Cardiotoxicity of novel agents [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED13-1.

Background During the COVID pandemic, we designed and implemented a program, called BQual-D, to maintain high quality care for patients with HR+, HER2 negative MBC who were taking oral anti-cancer therapy and needed to shelter at home. This program augmented available clinical resources with (1) trained nurse coaches to manage side effects, improve adherence, monitor for cancer progression and screen for psychological distress via telehealth, and (2) a care coordinator to arrange blood testing at local labs to facilitate timely medication dose adjustments. BQual-D served patients from August 2020 through April 2021. Here, we describe survey results assessing patient (pt) satisfaction with BQual-D. Methods Pt’s satisfaction surveys included questions rated on a Likert scale (1 “strongly disagree” to 5 “strongly agree”) with questions regarding the following: satisfaction with the quality of the nurse coaching calls; perception that the nurse coach listened to what they were trying to convey; whether or not their needs were met by the nurse coaching calls; whether they felt that they received adequate explanation regarding the nurse coaching calls; whether they would recommend the nurse coaching calls to a friend; perception of whether or not the nurse coach was negative or critical towards them; whether or not they would do it over (i.e., if they would return to the nurse coaching calls); whether or not they felt that the nurse coach was friendly or warm toward them; they were able to more effectively deal with care and symptoms; they felt free to express themselves; they were able to focus on what was of real concern to them; the nurse seemed to understand what they were thinking and feeling. Patients were also asked how much the calls helped with their care and symptoms. Descriptive statistics are reported (i.e., frequencies and means). Results 84 pts were screened and contacted for the BQual-D program. Of the 64 pts who responded, 52 (81.3%) were interested and enrolled in BQual-D; 12 (18.8%) declined. Among those who enrolled, 1 voluntarily withdrew, and 7 withdrew due to change in treatment. Participants had a mean age of 65 (range 36 – 88 yrs) and the following racial distribution - Caucasian/White (38, 73.1%), Black or African American (12, 23.1%), American Indian (1, 1.9%) and American Indian or Alaskan Native (1, 1.9%). Satisfaction surveys were received from 32 (50%) pts. Results of surveys regarding patient satisfaction with the nurse coach were generally positive. Pts agreed or strongly agreed that they were satisfied with the quality of the nurse coaching calls (94%), the nurse coach listened to what they were trying to convey (94%), their needs were met by the nurse coaching calls (91%), they understood the purpose of the call (90%), and they would recommend the nurse coaching calls to a friend (88%). The majority (74%) agreed or strongly agreed that they were able to more effectively deal with their care and symptoms after the nurse coach calls. When asked how much the calls helped their care and symptoms, 61% indicated that they made things a lot better, 19% indicated that they made things somewhat better, 16% indicated that they made no difference. One patient indicated that the calls made things somewhat worse. Conclusions During the COVID pandemic, when sheltering at home was encouraged, patient satisfaction with BQual-D, which provided additional health resources (nurse coaches, care coordinator) to support pts on oral therapy for HR+ MBC, was high. Resources needed to implement BQual-D should be explored as a way of providing additional support for pts to minimize the requirement for in-person visits. Funding: Supported by a grant from Pfizer. Citation Format: Gretchen Kimmick, Smrithi Divakaran, Heather Moore, Cynthia Rose, Pamela Gentry, Michael Willis, Susan Dent, Sarah L. Sammons, Jeremy Force, Kelly Westbrook, Carey Anders, Rebecca Shelby. Best Quality of Care from a Distance (BQual-D): Maintaining high quality care for hormone receptor positive (HR+) metastatic breast cancer (MBC) during the COVID pandemic, patient participation and satisfaction with the program. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-51.

Background: Treatment for premenopausal women with high or intermediate risk hormone receptor (HR)+ breast cancer (BC) now includes the concurrent use of ovarian function suppression (OFS) and an aromatase inhibitor (AI) therapy to induce near complete estrogen deprivation (NCED). The long-term cardiovascular (CV) sequela for women treated with NCED is unknown. Premature menopause in the non-cancer population is associated with CV disease, including atherosclerosis and coronary artery disease, which can be detected pre-clinically by myocardial perfusion imaging and coronary artery plaques. This, together with the CV morbidity associated with other aspects of BC treatment and future life-years of these women, warrants further investigation with the goal of identifying pre-clinical markers of myocardial compromise. We seek to do this with the following specific aims: 1. Characterize and quantify the extent of coronary microvascular injury and perfusion changes experienced during early NCED therapy. 2. Characterize and quantify the extent of structural and functional alterations to the aorta and left ventricle while on NCED therapy. 3. Identify potential biomarkers and additional risk factors for CV morbidity in patients receiving NCEDTrial Design: This is a federally funded (NHLBI) prospective cohort study conducted at 3 regional NCI-supported Cancer Centers (Atrium Health Wake Forest Baptist, Virginia Commonwealth and Duke) that will include premenopausal women, age ≤ 55, with Stage I-III BC following completion of planned chemotherapy, surgery and radiation with an ECOG 0-1. HR+ BC patients will receive an AI and OFS. Women with HR- BC are included as comparators. CV imaging and biomarkers will be obtained at baseline, 1 year and 2 years (Table 1). These assessments will include serial cardiac magnetic resonance (CMR) and coronary computed tomography angiography (CCTA) imaging as well as laboratory measurements, including exploratory biomarkers. The primary outcome is myocardial perfusion reserve (MPR) as measured by CMR imaging stress studies. We will correlate CMR imaging with CCTA to provide complementary detail of coronary plaque changes. The study will also assess the relevance of pre-existing risk factors, including an emphasis on racial disparities, on study outcomes, and dynamic change in modifiable and treatment related risk factors. Statistical Methods: We plan to enroll 90 women, 67 in the NCED group and 23 in the HR-group, allowing for a 10% drop out rate. There are two primary types of statistical analyses. The first includes testing hypotheses between group (NCED vs HR-) and within group (longitudinal changes within the NCED group) for Aims 1 and 2. Comparisons will be made using longitudinal mixed models to examine effects on outcomes measured. The second analyses, for Aim 3, involve developing predictive equations utilizing a stepwise linear regression approach to determine if patient demographics, clinical parameters and serum biomarkers are associated with MPR. The sample size allows 80% power to address specific aims for between and within group comparisons, including a between group difference of 2.8% in our primary outcome, MPR. Present Accrual: 0 Target Accrual: 90 Contact information: Emily Douglas, MD; edouglas@wakehealth.edu Table 1: Study Procedures Citation Format: Emily Douglas, Nathaniel O’Connell, Mary Hackney, Wendy Bottinor, John Grizzard, Igor Klem, Carolyn Park, Sujethra Vasu, Karl Richardson, Susan Dent, Ralph D’Agostino, Gregory Hundley, Jennifer Jordan, Alexandra Thomas. The CROWN Study (CaRdiac Outcomes With Near complete estrogen deprivation): A multicenter, prospective cohort study of cardiovascular outcomes in premenopausal women treated with ovarian suppression and an aromatase inhibitor [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-01-05.

There are nearly 17 million cancer survivors in the United States, including those who are currently receiving cancer therapy with curative intent and expected to be long-term survivors, as well as those with chronic cancers such as metastatic disease or chronic lymphocytic leukemia, who will receive cancer therapy for many years. Current clinical practice guidelines focus on lifestyle interventions, such as exercise and healthy eating habits, but generally do not address management strategies for clinicians or strategies to increase adherence to medications. We discuss 3 cardiometabolic comorbidities among cancer survivors and present the prevalence of comorbidities prior to a cancer diagnosis, treatment of comorbidities during cancer therapy, and management considerations of comorbidities in long-term cancer survivors or those on chronic cancer therapy. Approaches to support medication adherence and potential methods to enhance a team approach to optimize care of the individual with cancer across the continuum of disease are discussed.

Cardiometabolic disease (CMD) is the most common preventable cause of death in the world. A number of components are included in the spectrum of CMD, such as metabolic syndrome/obesity, hyperglycemia/diabetes, dyslipidemia, and hypertension, which are independently associated with cardiovascular disease risk. These conditions often occur together, and patients with cancer frequently undergo treatments that can generate or worsen CMD. This review highlights and presents mechanistic and epidemiological evidence regarding CMD in four categories of anticancer medications, namely, mTOR/PI3K-Akt inhibitors, multi-targeted tyrosine kinase inhibitor (TKI), immune checkpoint inhibitor therapy, and endocrine therapy. Patients taking these medications need careful monitoring during therapy. There is a role for cardio-oncology and onco-primary care specialists in optimally managing patients at risk to mitigate CMD during treatment with these and other investigational anti-cancer medications.

Background: Trastuzumab (T) has improved patient (pt) outcomes in HER2+ breast cancer (BC) but carries a risk of cardiotoxicity. In the adjuvant setting, guidelines recommend cardiac monitoring (CM) every 3-4 months. In Ontario, Canada, pts with advanced BC (aBC) have CM every 6 months during HER targeted therapy, despite lack of evidence this practice improves patient outcomes. This study was conducted to understand predictive factors for cardiotoxicity and determine the impact of cardiovascular imaging in the HER2+ aBC population. Methods: This was a retrospective population-based cohort study of aBC pts treated with T (all lines), in Ontario (2007-17). Patient-level data was obtained using linked administrative databases through the Institute for Clinical Evaluative Sciences (ICES). The overall cohort was divided into two groups, those who developed a cardiac event and those who did not. In this study, a cardiac event (CE) was defined as new diagnosis of heart failure, cardiomyopathy or pulmonary edema between cycle 1 of T up to 90 days after final dose. Pts with pre-existing heart disease were excluded. Analysis included descriptive statistics for pt characteristics and logistic regression (LR) for factors predictive of CE. LR treated most patient characteristics as categorical values, including age in 10-year intervals ( Results: Of the 2284 pts with HER2+ aBC treated with T, 167 (7.3%) developed a CE. Median age first dose T was 57 (IQR 49 - 66); 61 (IQR 51-70) for pts with CE. Median cycles T 16 (IQR 7-32); 21 (IQR 8-45) for pts with CE (p60 (OR 5.21, 95% CI 1.83 -14.84, p=0.05) and higher number cycles of T (OR 1.01; 95% CI 1-101, p=0.0282). Conclusions: This is the first population-based study to report on cardiac events and cardiac monitoring in HER2 + aBC pts during T-based therapy. Older age and longer treatment with T were associated with increased risk of a CE. Most pts had CM in this cohort consistent with regional guidelines, however the group with no monitoring did not see increased rates of CEs. Future research should focus on evaluating the potential benefit of routine CM in aBC pts at greatest risk of experiencing a CE. Citation Format: Moira K Rushton-Marovac, Isac Lima, Meltem Tuna, Chiara Melloni, Kathy Pritchard, Steven Hawken, Susan F Dent. Cardiac monitoring in advanced breast cancer patients treated with trastuzumab: Does it improve cardiac safety? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-11.