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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.

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.

BackgroundRe-allocation of resources during the COVID-19 pandemic has resulted in delays in care delivery to patients with cardiovascular disease and cancer. The ability of health care providers to provide optimal care in this setting has not been formally evaluated.ObjectivesTo assess the impact of COVID-19 resource re-allocation on scheduling, testing, elective procedures, telemedicine access, use of new COVID-19 therapies, and providers’ opinions on healthcare policies among oncology and cardiology practitioners.MethodsAn electronic survey was conducted by a cardio-oncology collaborative network through regional and state chapters of the American College of Cardiology, American Society of Clinical Oncology, and the International Cardio-Oncology Society. Descriptive statistics were reported by frequency and proportion for analyses, and stratified categorically by geographic region and specialty.ResultsOne thousand four hundred fifteen providers (43 countries) participated: 986 cardiologists, 306 oncologists, and 118 trainees/internal medicine. 63% (195/306) of oncologists vs 92% (896/976) of cardiologists reported cancellations of treatments/elective procedures (p = 0.01). 46% (442/970) of cardiologists and 25% (76/303) of oncologists modified the scope of their practice (p = p = 0.018). Telemedicine was less common in Europe 81% (74/91), and Latin America 64% (101/158), than the United States, 88% (950/1097) (p = ConclusionsThese results support initiatives to promote expanded coverage for telemedicine, increased access to PPE, better testing availability and involvement of medical professional societies to help with preparedness for future health care crisis.

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.

Background As treatments for cancer have improved, more people are surviving cancer. However, compared to people without a history of cancer, cancer survivors are more likely to die of cardiovascular disease (CVD). Increased risk for CVD-related mortality among cancer survivors is partially due to lack of medication adherence and problems that exist in care coordination between cancer specialists, primary care physicians, and cardiologists. Methods/Design The Onco-primary care networking to support TEAM-based care (ONE TEAM) study is an 18-month cluster-randomized controlled trial with clustering at the primary care clinic level. ONE TEAM compares the provision of the iGuide intervention to patients and primary care providers versus an education-only control. For phase 1, at the patient level, the intervention includes video vignettes and a live webinar; provider-level interventions include electronic health records-based communication and case-based webinars. Participants will be enrolled from across North Carolina one of their first visits with a cancer specialist (e.g., surgeon, radiation or medical oncologist). We use a sequential multiple assignment randomized trial (SMART) design. Outcomes (measured at the patient level) will include Healthcare Effectiveness Data and Information Set (HEDIS) quality measures of management of three CVD comorbidities using laboratory testing (glycated hemoglobin [A1c], lipid profile) and blood pressure measurements; (2) medication adherence assessed pharmacy refill data using Proportion of Days Covered (PDC); and (3) patient-provider communication (Patient-Centered Communication in Cancer Care, PCC-Ca-36). Primary care clinics in the intervention arm will be considered non-responders if 90% or more of their participating patients do not meet the modified HEDIS quality metrics at the 6-month measurement, assessed once the first enrollee from each practice reaches the 12-month mark. Non-responders will be re-randomized to either continue to receive the iGuide 1 intervention, or to receive the iGuide 2 intervention, which includes tailored videos for participants and specialist consults with primary care providers. Discussion As the population of cancer survivors grows, ONE TEAM will contribute to closing the CVD outcomes gap among cancer survivors by optimizing and integrating cancer care and primary care teams. ONE TEAM is designed so that it will be possible for others to emulate and implement at scale. Trial registration This study (NCT04258813) was registered in clinicaltrals.gov on February 6, 2020.

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.

Background: Modern breast cancer (BC) therapies have led to significant improvement in disease free and overall survival, but are associated with off target toxicity including cardiotoxicity. Current cardio-protective strategies have included all patients (pts) receiving potential cardiotoxic cancer therapy with modest clinic benefit. In this pilot study, we examined the role of cardioprotective therapy (CPT) in BC pts identified as having subclinical or clinical cardiotoxicity. Methods: Early BC patients (pts) in the PREFECT Study (NCT03543228) were serially examined for cardiac function up to 1-year after initiation of chemotherapy (CT) using cardiac magnetic resonance (CMR) imaging. CT included epirubucin and cyclophosphamide every 2 weeks x 4 followed by paclitaxel (weekly x 12 or every 2 weeks x 4) and targeted therapy (e.g trastuzumab) if human epidermal growth factor receptor 2 (HER2) positive. Myocardial strain was quantified using fast-strain encoded (fast-SENC) across 37 left and 11 right ventricular segments. The percent of segments with normal strain (≤17%) was calculated (% normal MyoStrain). Clinical cardiotoxicity (CTx) was defined as an absolute change in left ventricular ejection fraction (LVEF) > 10 % to below 53 %; subclinical CTx was defined as an asymptomatic decrease in LVEF of 15 % or worsening global longitudinal strain (GLS) > 15 %, or abnormal cardiac biomarkers (troponin, brain natriuretic peptide (BNP), N terminal-BNP). Descriptive statistics were used to summarize subject demographics, medical history, cardiovascular measures, and response to CPT. Response to CPT was defined as restoration of cardiac function, wall motion, absence of cardiac symptoms, and normalization of cardiac biomarkers. Results: A total of 40 BC pts age 50 (+/- 12.5) years and body mass index of 25.4 (+/- 5.8 kg/m2) were enrolled and followed for 273 +/- 126 days. Clinical CTx was observed in 4 (10 %) patients and subclinical CTx in 15 (37.5%). Pts with clinical CTx were older, had a higher Charlson co-morbidity index, and had significantly reduced cardiac function (49.5% +/- 9.5% normal MyoStrain) despite normal CMR LVEF (54.2% +/- 4.0%). Pts with subclinical CTx had a smaller decline in cardiac function (58.6% +/- 9.1% normal MyoStrain) despite normal CMR LVEF (56.4% +/- 4.9%). 12/19 pts with CTx showed improvement with CPT (candesartan -9, ramipril -2, lisinopril -1, and beta-blockers (BB): yes -8, no -4); 1 did not improve, 4 did not receive CPT and 2 remained on ineffective anti-hypertensive medication. Pts at baseline, without CTx, or showing improvement based on CPT, had significantly higher % normal MyoStrain (79.0% +/- 11.8%, 79.5% +/- 9.3%, and 80.4% +/- 9.8% respectively) and normal CMR LVEF (59.7% +/- 4.2%, 59.9% +/- 4.9%, and 60.7% +/- 5.1% respectively). Discussion: Identifying BC pts at high risk of experiencing cancer therapy related cardiotoxicity enables a more tailored approach to cardio-preventative strategies. In this pilot study the majority (12/19) of BC pts identified with subclinical or clinical CTx demonstrated improvement in cardiac function with CPT. Proactive tailored cardio-protection may also prevent long term permanent cardiac dysfunction and associated heart failure. Larger, multi-center trials are warranted to evaluate the short and long term benefits of CPT in this pt population. Citation Format: Susan Faye Dent, Henning Steen, Moritz Montenbruck, Sebastian Esch, Pia Wulfing, Kyle Janson, Daniel Lenihan. Cardioprotective therapy in breast cancer patients with subclinical and clinical cardiotoxicty [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 P5-14-18.

Background: The APHINITY trial demonstrated that pertuzumab, when added to adjuvant trastuzumab and chemotherapy, modestly but statistically significantly improved invasive disease-free survival (IDFS) among patients with HER2-positive, operable breast cancer. From November 2011 until August 2013, 2400 patients were randomly assigned to receive pertuzumab and 2405 to receive placebo. The clinical cut off-date for the primary analysis was 19 Dec 2016 after a median follow-up of 45.4 months. In the intent-to-treat (ITT) population, the estimates of the 3-year rates of IDFS were 94.1% in the pertuzumab group and 93.2% in the placebo group (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.66 to 1.00; P=0.045). The benefit appeared more pronounced in patients with node-positive disease, with a HR of 0.77 (95% CI 0.62-0.96), and in those with hormone receptor-negative disease, where the HR was 0.76 (95% CI 0.56-1.04). Based on these results, pertuzumab in combination with trastuzumab was approved for high risk early HER2-positive breast cancer patients. The first interim analysis of OS took place at that same time. A total of 169 patients had died, with no significant treatment effect with regards to mortality found at that time. Diarrhea, grade 3 or higher, was more frequent within the pertuzumab group (9.8%) compared with the placebo group (3.7%). Heart failure, cardiac death, and cardiac dysfunction were infrequent in both treatment groups. Results: At 74.1 months of median follow-up (clinical cut-off date June 19, 2019), we now report results of the pre-planned, calendar-driven second interim OS analysis which requires a p-value of 0.0012 to reach statistical significance. Updated descriptive analyses of IDFS and cardiac safety were also performed. Fewer deaths were observed in the pertuzumab (P) arm [125 (5.2%) vs 147 (6.1%)], however statistical significance was not reached at this interim analysis. The hazard ratio for OS is 0.85 [95% CI 0.67-1.07 (p=0.17)]; 6-year OS percents are 94.8% vs 93.9% (0.9% difference).Updated IDFS results based on 508 events in the ITT population are: hazard ratio 0.76 [95% CI 0.64-0.91]; 6-year IDFS percents are 90.6% vs 87.8% (2.8% difference). Of note, the difference was due mainly to the reduction in distant (5.9% vs 7.7%) and loco-regional (1.2% vs 2.0%) BC relapses. The node-positive cohort continues to derive clear benefit from the addition of P: hazard ratio 0.72 (95% CI 0.59-0.87). The benefit in terms of 6-year IDFS percent is 4.5% [87.9% vs 83.4%].In the node-negative cohort, the IDFS hazard ratio is 1.02 (95% CI; 0.69-1.53) with 95% of patients being event-free in both arms at 6 years.With longer follow up, a treatment benefit of P is also seen in the hormone receptor (HR) positive cohort: IDFS hazard ratio for HR positive is 0.73 (95% CI 0.59 -0.92). IDFS hazard ratio for HR negative is 0.83 (95% CI 0.63 -1.10). No new cardiac safety concerns emerged. One additional primary cardiac event (heart failure) was reported in the P arm and 1 additional patient in each arm had a secondary cardiac event resulting to 18 and 8 for primary cardiac events and 65 and 68 for secondary cardiac events in the P and placebo arms, respectively. The benefit of P in HER2+ early BC is maintained, with the greatest benefit continuing to be observed in the node positive population. With longer follow-up, the benefit of P no longer appears to depend on HR status. Continued follow up of patients is very important to determine possible benefit for OS. A calendar-driven third interim OS analysis is planned in 2.5 years, and the event-driven final OS analysis is planned when 640 deaths have occurred. Citation Format: Martine Piccart, Marion Procter, Debora Fumagalli, Evandro de Azambuja, Emma Clark, Michael S. Ewer, Eleonora Restuccia, Guy Jerusalem, Susan Dent, Linda Reaby, Hervé Bonnefoi, Ian Krop, Tsang-Wu Liu, Tadeusz Pieńkowski, Masakazu Toi, Nicolas Wilcken, Michael Andersson, Young-Hyuck Im, Ling-Ming Tseng, Hans-Joachim Lueck, Marco Colleoni, Estefania Monturus, Mihaela Sicoe, Sébastien Guillaume, José Bines, Richard Gelber, Giuseppe Viale, Christoph Thomssen. Interim overall survival analysis of APHINITY (BIG 4-11): A randomized multicenter, double-blind, placebo-controlled trial comparing chemotherapy plus trastuzumab plus pertuzumab versus chemotherapy plus trastuzumab plus placebo as adjuvant therapy in patients with operable HER2-positive early breast cancer [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 GS1-04.

Background: Meta-analyses have demonstrated that young women ≤40 (YW) derive the most benefit from chemotherapy (EBCTCG, Lancet. 1998). Oncotype DX was designed to determine the benefit of chemotherapy in women with ER+/HER2-, node-negative (LN-) breast cancer based on recurrence score (RS). TAILORx reported clinically meaningful benefits in freedom-from-distant recurrence in women Methods: Using the National Cancer Data Base (NCDB), we identified individuals age 25) RS. Age categories were classified as ≤40, 41-50, and >50. Chi-square tests or Fisher’s exact tests were used to compare categorical variables. Logistic regression was used to estimate the association of RS score and age group with adjuvant chemotherapy use, after adjustment for known covariates. Kaplan-Meier curves were used to visualize unadjusted overall survival (OS), and Cox proportional hazards models were used to estimate adjusted OS. Results: 120,051 women were identified, of whom 4,781 were ≤40 years, 24,846 were 41-50, and 90,424 were >50. By age group, 20% of YW had a high RS compared to 12% of women age 41-50 and 15% of women >50 (p50 to receive chemotherapy (p Conclusions: High RS is more common in YW (≤40) than those age 41-50 or >50, and is associated with worse OS. YW with an int or low RS are more likely to receive chemotherapy despite unclear benefit. Chemotherapy was omitted in over half of YW with RS of 16-25, highlighting the uncertainty in clinical practice which will remain until further studies inform optimal systemic treatment specific to YW. 1. Sparano, J.A., et al., Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer. New England Journal of Medicine, 2019. 380(25): p. 2395-2405. Citation Format: Sarah Sammons, Yi Ren, Jeremy Force, Oluwadamilola M. Fayanju, Laura H. Rosenberger, Jennifer K. Plichta, Gretchen Kimmick, Kelly Westbrook, Susan Dent, Carey Anders, Samantha M. Thomas, Terry Hyslop, E. S. Hwang, P. K. Marcom, Rachel A. Greenup. Characterization of oncotype DX recurrence score and chemotherapy utilization patterns in young women (≤40) with early stage ER+/HER-, lymph node negative breast cancer [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 P3-08-10.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with backbone endocrine therapy have markedly improved progression-free survival and overall survival over endocrine therapy alone in advanced hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer and are the standard of care in the first- or second-line setting. There are few data to drive decision making for subsequent treatment strategies after inevitable disease progression after CDK4/6i. Information about the genomic landscape of CDK4/6i-resistant disease is emerging. Resistance mechanisms appear to be varied, but mutations in PIK3CA and ESR1, which can be acquired while receiving treatment, are frequent. Activating PIK3CA mutations are present in up to 35% of patients and are now the most actionable genomic alteration in HR+/HER2- advanced breast cancer with the recent approval of alpelisib and fulvestrant. Everolimus-based combinations and chemotherapy appear to have continued efficacy after progression while receiving CDK4/6i, although historical data on benefit include CDK4/6i-naive patients. Use of selective estrogen down-regulators over aromatase inhibitors is best once the patient has an acquired ESR1 mutation. Tumor biopsy with genomic sequencing and repeat biomarker analysis in patients with CDK4/6i- and endocrine-resistant disease will be integral to guide subsequent treatment strategies and to inform clinical trial eligibility. Promising novel therapeutics in CDK4/6i-resistant disease including oral selective estrogen down-regulators, fibroblast growth factor receptor antagonists, and immunotherapy will be discussed.

Session V of the Colloquium was chaired by Professors Teresa Lopez-Fernandez of Spain and Grzegorz Opolski of Poland. The 3 speakers addressed cardio-oncology issues as they relate to both clinical studies and real life situations. Professor Susan Dent discussed cardio-oncology networks for patients, emphasizing the importance of establishing a framework where the expertise of the cardiology consultant can supplement and reinforce the goals of optimal cancer therapy. Professor Thomas Suter moved the discussion further, sharing his insight into cardiac monitoring in clinical trials, emphasizing the lack of uniform criteria and lack of consensus regarding reversibility of cardiac events and long-term implications of modest declines in systolic function frequently found in clinical trials for which long-term follow-up may not be a component of the trial. Professor Giorgio Minotti added important considerations to the discussion of clinical trials. He emphasized that the usual reporting of cardiac systolic function omits important diastolic dysfunction data generated but often ignored during the routine cardiac exams. The inclusion of cardiac biomarker changes would also help to broaden the perspective of cardiac effects and events seen in patients enrolled in clinical trials.

The discipline of cardio-oncology has expanded at a remarkable pace. Recent developments and challenges to clinicians who practice cardio-oncology were presented at the Global Cardio-Oncology Summit on October 3 to 4, 2019, in São Paulo, Brazil. Here, we present the top 10 priorities for our field that were discussed at the meeting, and also detail a potential path forward to address these challenges. Defining robust predictors of cardiotoxicity, clarifying the role of cardioprotection, managing and preventing thromboembolism, improving hematopoietic stem cell transplant outcomes, personalizing cardiac interventions, building the cardio-oncology community, detecting and treating cardiovascular events associated with immunotherapy, understanding tyrosine kinase inhibitor cardiotoxicity, and enhancing survivorship care are all priorities for the field. The path forward requires a commitment to research, education, and excellence in clinical care to improve our patients' lives., Central Illustration, Highlights • The discipline of cardio-oncology has enjoyed extensive and complex development at a breathtaking pace. • Extensive ongoing clinical and basic research continue to shape and formulate the practice of cardio-oncology. • The path forward for the field needs to be centered on excellence in clinical care, transformative research, and broad education principles.

Background Cardio-oncology is a young sub-specialty that addresses the needs of cancer patients at risk of, or who have experienced cancer therapy related cardiac dysfunction (CTRCD). This study assessed clinicians’ understanding of cardio-oncology, opinions towards current practice, and approach to diagnosing and managing CTRCD. Methods A 45-question survey was administered online via Survey Monkey and WeChat to health care providers (HCPs) comprising of cardiologists, oncologists, and others from September 2017 to March 2018. Implementation of the survey followed a modified Dillman’s Total Design Method. Results In total, 160 responses were collected from 22 countries; majority were from cardiologists (53.8%) and oncologists (32.5%). The remaining 13.7% identified themselves as “others,” including general internists, cardio-oncologists, pediatric oncologists, radiation oncologists, cardiac rehabilitation therapists, nurse practitioners, research students, and pharmacists. In the setting of metastatic cancer, there was a difference in risk tolerance for cardiotoxicity between subspecialties. In this case, more cardiologists (36.7%) accepted a 5–10% risk of cardiotoxicity compared to oncologists (20.0%). Majority of cardiologists felt that cardiotoxicity should be monitored, even in asymptomatic cancer patients (55.8%). Only 12% of oncologists selected this response. In contrast, 50.0% of oncologists reported that cardiologists should be involved only when patients develop cardiotoxicity. In comparison, 6.5% of cardiologists selected this response. Majority of cardiologists stated that cardio-oncology clinics would significantly improve cancer patients’ prognosis (88.3%); only 45.8% of oncologists shared this opinion. Of all respondents, 66.9% stated they were familiar with a variety of international guidelines for managing cardiotoxicity. Of all oncologists, 65.3% indicated that they referred to these guidelines for clinical decision making. Conclusions Despite the growth of cardio-oncology clinics, there are significant knowledge gaps regarding prevention and treatment strategies for CTRCD among health care providers. Knowledge translation from guidelines and collaboration between cardiologists and oncologists are needed to improve cardiovascular outcomes of cancer patients. Electronic supplementary material The online version of this article (10.1186/s40959-019-0049-2) contains supplementary material, which is available to authorized users.

In breast cancer patients, coincidental detection of CAC at chest CT may be important in determining cardiovascular (CV) outcomes and facilitate CV disease primary prevention strategies.408 consecutive breast cancer patients referred to cardiac oncology clinic were included in the study. 256 patients without a prior history of coronary artery disease had undergone a chest CT. CT images were reviewed to detect CAC. Framingham risk score (FRS) was calculated and patient electronic medical records were interrogated to document the incidence of a composite clinical end point of all-cause mortality and cardiac events (coronary revascularization, heart failure hospitalization and de novo atrial fibrillation). Prevalence of statin prescribing was also collected.Patients were followed for a median of 6.5 years. 112 clinical events occurred. Clinical follow up was 98%. CAC was found in 26% of patients. On multivariable analysis, CAC and advance cancer stage, but not FRS predicted the composite clinical end point (OR for CAC 2.59, p 0.01). CAC but not FRS also predicted the incidence of cardiac events (OR for CAC 4.90, p 0.01). CAC was present in 7.3% of patients with low FRS; none had been prescribed a statin. In patients with CAC and FRS ≥ 10%, 45% were not on a statin.CAC is a common coincidental finding at CT chest in breast cancer patients referred to cardiac oncology. CAC but not FRS was predictive of composite clinical events and cardiac events. Detection of CAC at chest CT could alter the prescribing of primary prevention strategies to help prevent future cardiac events in breast cancer patients.

Purpose of Review HER2-targeted therapies have led to improved clinical outcomes in early and advanced breast cancer (BC). We review the long-term cardiotoxicity of HER2-targeted therapy in early and advanced BC, our current knowledge of cardiotoxicity of novel HER2-targeted therapies, and propose a cardiac monitoring (CM) strategy for this population. Recent Findings Long-term data from studies with HER2-targeted therapy in the adjuvant setting have failed to demonstrate an increase in cardiotoxicity over time, and rates of cardiotoxicity seen with novel HER2 agents remain low. Despite over a decade of experience with HER2-targeted therapy, CM in clinical practice is inconsistent in patients with early BC and almost non-existent in advanced BC. Summary Long-term follow-up of clinical trials with HER2-targeted agents in early and advanced BC has failed to demonstrate increased rates of cardiotoxicity over time, attesting to the long-term safety of this class of drugs for the majority of patients, although the long-term cardiac safety of newer HER2 agents in the non-clinical trial setting is largely unknown. We propose CM incorporating clinical history, cardiac imaging, and biomarkers.

Purpose CompLEEment-1 is a phase 3b trial in an expanded patient population with hormone receptor-positive (HR +), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC), the largest current trial of cyclin-dependent kinase 4 and 6 inhibitors in ABC. Methods Patients treated with ≤ 1 line of prior chemotherapy and no prior endocrine therapy for ABC received ribociclib 600 mg/day (3-weeks-on/1-week-off) plus letrozole 2.5 mg/day and additionally monthly goserelin/leuprolide in men and pre-/perimenopausal women. Eligibility criteria allowed inclusion of patients with stable CNS metastases and an Eastern Cooperative Oncology Group performance status of 2. Primary objectives were safety and tolerability, and secondary objectives were efficacy and quality of life (QoL). Results Overall, 3,246 patients were evaluated (median follow-up 25.4 months). Rates of all-grade and grade ≥ 3 treatment-related adverse events (AEs) were 95.2% and 67.5%, respectively. Treatment-related discontinuations due to all grade and grade ≥ 3 AEs occurred in 12.9% and 7.3% of patients, respectively. Rates of all-grade AEs of special interest (AESI) were as follows: neutropenia (74.5%), increased alanine aminotransferase (16.2%), increased aspartate aminotransferase (14.1%), and QTcF prolongation (6.7%); corresponding values for grade ≥ 3 AESI were 57.2%, 7.7%, 5.7%, and 1.0%, respectively. Median time to progression was 27.1 months (95% confidence interval, 25.7 to not reached). Patient QoL was maintained during treatment. Conclusion Safety and efficacy data in this expanded population were consistent with the MONALEESA-2 and MONALEESA-7 trials and support the use of ribociclib plus letrozole in the first-line setting for patients with HR + , HER2– ABC. Trial registration linicalTrials.gov NCT02941926.

With the advent of novel cancer therapeutics and improved screening, more patients are surviving a cancer diagnosis or living longer with advanced disease. Many of these treatments have associated cardiovascular toxicities that can manifest in both an acute and a delayed fashion. Arrhythmias are an increasingly identified complication with unique management challenges in the cancer population. The purpose of this scientific statement is to summarize the current state of knowledge regarding arrhythmia identification and treatment in patients with cancer. Atrial tachyarrhythmias, particularly atrial fibrillation, are most common, but ventricular arrhythmias, including those related to treatment-induced QT prolongation, and bradyarrhythmias can also occur. Despite increased recognition, dedicated prospective studies evaluating true incidence are lacking. Moreover, few studies have addressed appropriate prevention and treatment strategies. As such, this scientific statement serves to mobilize the cardio-oncology, electrophysiology, and oncology communities to develop clinical and scientific collaborations that will improve the care of patients with cancer who have arrhythmias.

Supplemental Digital Content is available in the text., Background: Our goal was to evaluate the ability of cardiovascular magnetic resonance for detecting and predicting cardiac dysfunction in patients receiving cancer therapy. Left ventricular ejection fraction, global and regional strain utilizing fast-strain-encoded, T1 and T2 mapping, and cardiac biomarkers (troponin and BNP [brain natriuretic peptide]) were analyzed. Methods: Sixty-one patients (47 with breast cancer, 11 with non-Hodgkin lymphoma, and 3 with Hodgkin lymphoma) underwent cardiovascular magnetic resonance scans at baseline and at regular intervals during 2 years of follow-up. The percentage of all left ventricular myocardial segments with strain ≤−17% (normal myocardium [%]) was analyzed. Clinical cardiotoxicity (CTX) and sub-CTX were defined according to standard measures. Results: Nine (15%) patients developed CTX, 26 (43%) had sub-CTX. Of the 35 patients with CTX or sub-CTX, 24 (69%) were treated with cardioprotective medications and showed recovery of cardiac function. The amount of normal myocardium (%) exhibited markedly higher accuracy for the detection of CTX and sub-CTX compared with left ventricular ejection fraction, T1, and T2 mapping as well as troponin I (Δareas under the curve=0.20, 0.24, and 0.46 for normal myocardium (%) versus left ventricular ejection fraction, troponin I, and T1 mapping, P

CDK 4/6 inhibitors, in combination with endocrine therapy, are the standard of care for patients with endocrine-sensitive advanced breast cancer. This class of drug, however, is associated with QT prolongation, which serves as a surrogate marker for Torsades de Pointes (TdP), a cause of life-threatening ventricular arrhythmias and sudden cardiac death. The ICH E14 guidance document uses the Bazett formula for reporting of cardio-dynamic and safety ECG data in clinical trials. While there is substantial familiarity with the Bazett (QTcB) formula (QT/(RR) 1/2), the Fridericia (QTcF) formula (QT/(RR) 1/3 ) is preferred in the cancer population as it is often more accurate at heart rate extreme. Accordingly, the Fridericia formula is currently the standard adopted by the FDA when submitting QT data for review. At the King Faisal Specialist Hospital and Research Center, a total of 82 patients with advanced breast cancer, had a baseline ECG on day 1 before the initiation of ribociclib based therapy. Of the enrolled 82 patients, 19 (23%) were initially excluded from receiving ribociclib based due to a prolonged QTc >450ms, however, when the QTc-interval was manually measured and recalculated using Fridericia and Framingham formulae using MDCalC (https//:www.mdcalc.com),17 of 19 patients successfully received their treatment without any arrhythmogenic effects. Repeat ECG on day14, and day 1 of cycle 2 demonstrated that none of these patients had QTc exceeding 480 ms. Our data highlights the complexities of evaluating the QT interval in oncology patients and the utility of the Fridericia/Framingham formulae in this population. Given these findings, we recommend the adoption of the Fridericia or Framingham formulae for measurement of QTc in all cancer patients exposed to potentially QT-prolonging cancer therapy.

Purpose of Review To give an overview of the role of social media (SoMe) in cardio-oncology during the COVID-19 pandemic. Recent Findings SoMe has been critical in fostering education, outreach, awareness, collaboration, dissemination of information, and advocacy in cardio-oncology. This has become increasingly evident during the COVID-19 pandemic, during which SoMe has helped share best practices, community, and research focused on the impact of COVID-19 in cardiology and hematology/oncology, with cardio-oncology at the interface of these two subspecialty fields. Summary A strength of SoMe is the ability to amplify a message in real-time, globally, with minimal investment of resources. This has been particularly beneficial for the emerging field of cardio-hematology/cardio-oncology, a field focused on the interplay of cancer and cardiovascular disease. SoMe field especially during the COVID-19 pandemic. We illustrate how social media has supported innovation (including telemedicine), amplification of healthcare workers’ voice, and illumination of pre-existing and continued health disparities within the field of cardio-oncology during the pandemic.

Background: The literature suggests that medical oncologists differ on how they use the Oncotype DX (ODX) genomic assay for making decisions about systemic therapy in breast cancer patients. Given the emergence of data supporting the use of genomic profiling for the prognosis and predicting benefit of chemotherapy, we surveyed medical oncologists in Canada to assess their usage and perception of the ODX assay. Methods: A 34-item survey was distributed to Canadian medical oncologists via the Canadian Association of Medical Oncologists. Data was collected on physician demographics, ODX usage patterns, and physicians’ perception of the impact clinical and pathologic characteristics make on ODX utilization. Results: Response rate was 20.6% with 47 responses received from 228 survey sent. Forty-five responses were eligible for analysis. Sixty-two percent (28/45) of respondents treated predominantly breast cancer, and 60% (27/45) have been in practice for at least 10 years. The most cited reason for using ODX was to avoid giving patients unnecessary chemotherapy (64%, 29/45). Sixty-seven percent (30/45) deferred making treatment decisions until ODX testing was completed. Factors most strongly impacting ODX utilization included: patient request, medical comorbidities and tumor grade. In clinical scenarios, ODX was more frequently selected for patients aged 40–65 (vs. &lt, 40 or &gt, 65), grade 2 tumors (vs. grade 1 or 3), and Ki-67 index of 10–20% (vs. &lt, 10% or &gt, 20%). Conclusions: This survey demonstrated that Canadian medical oncologists are preferentially using ODX to avoid giving patients unnecessary chemotherapy. The utilization of ODX is mainly in patients with intermediate clinical and pathologic features.

The innovative development of cancer therapies has led to an unprecedented improvement in survival outcomes and a wide array of treatment-related toxicities, including those that are cardiovascular in nature. Aging of the population further adds to the number of patients being treated for cancer, especially those with comorbidities. Such pre-existing and developing cardiovascular diseases pose some of the greatest risks of morbidity and mortality in patients with cancer. Addressing the complex cardiovascular needs of these patients has become increasingly important, resulting in an imperative for an intersecting discipline: cardio-oncology. Over the past decade, there has been a remarkable rise of cardio-oncology clinics and service lines. This development, however, has occurred in a vacuum of standard practice and training guidelines, although these are being actively pursued. In this council perspective document, the authors delineate the scope of practice in cardio-oncology and the proposed training requirements, as well as the necessary core competencies. This document also serves as a roadmap toward confirming cardio-oncology as a subspecialty in medicine.

Background Cancer treatments (CT) have been shown to occasionally elicit a toxic reaction on the heart. Echocardiography (ECHO) and cardiac magnetic resonance imaging (CMR) have been used to monitor cardiotoxicity through left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). Fast-SENC (fSENC) CMR testing directly measures intramyocardial contraction to quantify subtle changes in function capable of detecting cardiotoxicity missed by conventional imaging modalities. The PREFECT study compares fast-SENC vs ECHO in terms of sensitivity of predicting and detecting subclinical (sCTX) or clinical cardiotoxicity (cCTX) irrespective of loading conditions or changes in cardiac output. Methods A single center, prospective clinical trial of patients receiving anthracycline-based CT had fSENC acquired during CMR exams with a 1.5T scanner. Intramyocardial LV & RV strain was quantified with MyoStrain software. Three short axis scans (basal, midventricular, & apical) were used to calculate peak strain in 16 LV & 6 RV longitudinal segments while three long axis scans (2-, 3-, & 4-chamber) were used to calculate 21 LV & 5 RV circumferential segments. Results 63 patients had 323 scans; 41% experienced sCTX and 15% cCTX. Figure 1 shows a Box and Whisker's plot for the % of fSENC ≤−17 by cardiotoxicity status. Both fSENC and CMR LVEF detected sCTX and cCTX based on ANOVA analysis (p Conclusion Segmental fSENC detected early CT-induced sCTX regardless of loading conditions. ECHO did not detect sCTX potentially due to compensatory mechanisms or acoustic window limitations in breast cancer and lymphoma patients that had less effect on CMR. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Myocardial solution (MSI)

BackgroundRe-allocation of resources during the COVID-19 pandemic has resulted in delays in care delivery to patients with cardiovascular disease and cancer. The ability of health care providers to provide optimal care in this setting has not been formally evaluated.ObjectivesTo assess the impact of COVID-19 resource re-allocation on scheduling, testing, elective procedures, telemedicine access, use of new COVID-19 therapies, and providers’ opinions on healthcare policies among oncology and cardiology practitioners.MethodsAn electronic survey was conducted by a cardio-oncology collaborative network through regional and state chapters of the American College of Cardiology , American Society of Clinical Oncology, and the International Cardio-Oncology Society. Descriptive statistics were reported by frequency and proportion for analyses, and stratified categorically by geographic region and specialty.Results1,415 providers (43 countries) participated: 986 cardiologists, 306 oncologists, and 118 trainees/internal medicine. 63% (195/306) of oncologists vs 92% (896/976) of cardiologists reported cancellations of treatments/elective procedures (p=0.01). 46% (442/970) of cardiologists and 25% (76/303) of oncologists modified the scope of their practice (p=ConclusionsThese results support initiatives to promote expanded coverage for telemedicine, increased access to PPE, better testing availability and involvement of medical professional societies to help with preparedness for future health care crisis.Appendix: Link to the Survey: https://www.surveymonkey.com/r/C8ZDYNW

Coronavirus disease 2019 (COVID‐19) has emerged as a global pandemic and public health crisis. Increasing waves of intermittent infectious outbreaks have dramatically influenced care among broad populations. Over the past 2 decades, there has been a rapid increase in cancer survival, with >400 000 new survivors each year. The increasingly common presence of cardiovascular disease in patients during or after cancer treatment led to the rapid growth of the field of cardio‐oncology with a mandate of identifying, treating, and preventing the various forms of cardiovascular disease seen among this population. This review evaluates the implications of the pandemic on the practice and study of cardio‐oncology. The evolving understanding of the relationship between comorbid disease and clinical outcomes among this population is assessed. With the impetus of the pandemic, cardio‐oncology can be deliberate in embracing changes to cardiac screening, monitoring, and intervention during oncology care. Bridging 2 specialties, consideration of the lessons learned in cancer and cardiovascular may pivotally inform ongoing therapeutic efforts. Further, the development of multicenter registries focused on understanding and optimizing outcomes among these patients should be considered. Together, these insights may critically inform strategies for the care of cardio‐oncology patients in future phases of the COVID‐19 pandemic and beyond.

In response to the coronavirus disease 2019 (COVID-19) pandemic, the Cardio-Oncology and Imaging Councils of the American College of Cardiology offers recommendations to clinicians regarding the cardiovascular care of cardio-oncology patients in this expert consensus statement. Cardio-oncology patients—individuals with an active or prior cancer history and with or at risk of cardiovascular disease—are a rapidly growing population who are at increased risk of infection, and experiencing severe and/or lethal complications by COVID-19. Recommendations for optimizing screening and monitoring visits to detect cardiac dysfunction are discussed. In addition, judicious use of multimodality imaging and biomarkers are proposed to identify myocardial, valvular, vascular, and pericardial involvement in cancer patients. The difficulties of diagnosing the etiology of cardiovascular complications in patients with cancer and COVID-19 are outlined, along with weighing the advantages against risks of exposure, with the modification of existing cardiovascular treatments and cardiotoxicity surveillance in patients with cancer during the COVID-19 pandemic.

OBJECTIVE The three Magee Equations provide an estimate of the Oncotype DX recurrence score using commonly available clinicopathologic information (tumour size, grade, oestrogen receptor, progesterone receptor, HER2, and Ki67). We assessed whether integration of Magee Equations into routine clinical practice affected the frequency of Oncotype DX requests. METHODS Patients with newly diagnosed, node negative, hormone receptor positive, and HER2 negative invasive breast cancer were randomized to undergo a Magee calculation or not. At the first clinic assessment, the oncologist was provided with all routinely available clinicopathologic information (including Ki67) either with or without the results of Magee Equations. Primary outcome was frequency of Oncotype DX ordering. Secondary outcomes included frequency of chemotherapy use, time to commencement of radiotherapy, or systemic therapy. Physician comfort with systemic therapy choices and the use of Ki67 and Magee Equations was also assessed. RESULTS Data from 175 randomized patients was available, 84 patients (48%) with and 91 (52%) without calculated Magee Equations. Oncotype DX was ordered in 10 (12.05%) and 13 (14.44%) (RR 0.83, 0.39-1.80; P = 0.64) in the Magee and no Magee groups, respectively. There were no statistically or clinically significant differences between the randomized groups for any of the secondary outcomes. Availability of both Ki67 and Magee Equations was associated with increased physician comfort around systemic treatment decisions. CONCLUSIONS In a practice where Ki67 is routinely available, addition of Magee Equations into routine clinic practice was not associated with a reduction in Oncotype DX use. Availability of both Ki67 and Magee Equations did however increase physician comfort with systemic therapy decisions.

BackgroundAdjuvant trastuzumab for early-stage (I-III) HER2-positive breast cancer (BC) has led to statistically significant improvement in cancer outcomes but carries a risk of cardiotoxicity. Trastuzumab is discontinued early in many patients for asymptomatic changes in left ventricular ejection fraction. We evaluated the impact of early discontinuation of trastuzumab on cancer outcomes.MethodsWe conducted a retrospective population-based cohort study of early BC patients treated with adjuvant trastuzumab in Ontario, Canada, 2007-2016. Four groups were analyzed: group A was full treatment, 17-18 cycles trastuzumab; group B was cardiac event (CE) within treatment period; group C was ≤16 cycles, no CEs, stopped within 30 days from last cardiac imaging; and group D was ≤16 cycles, no CEs, stopped more than 30 days from cardiac imaging. Primary outcome was disease-free survival (DFS); secondary outcomes were: overall survival, cancer-specific mortality, and cardiovascular mortality. Sensitivity analyses were performed 14 months after cycle 1 trastuzumab to control for early relapse.ResultsA total of 5547 patients met the inclusion criteria: group A = 3921, group B = 309, group C = 362, and group D = 955. The 5-year DFS was 94.1% in group A, 80.1% in group B, 81.4% in group C, and 82.4% in group D. Using a Cox model, the hazard ratio for 5-year DFS was 3.15 (95% confidence interval [CI] = 2.13 to 4.65) for group B, 1.94 (95% CI = 1.30 to 2.89) for group C, and 1.92 (95% CI = 1.46 to 2.53) for group D. Overall, 26 patients (0.5%) died of cardiac causes.ConclusionsBC patients in Ontario who did not complete adjuvant trastuzumab had a statistically significantly higher risk of BC relapse and death and low incidence of cardiac death. These findings support 1 year of adjuvant trastuzumab in early-stage BC.

Advances in cancer screening and improved treatment approaches have led to an increase in survivorship and, consequently, recognition of an association between cancer treatments and the development of cardiovascular complications. In addition, as the population becomes proportionally older, comorbid cardiovascular risk factors are more prevalent in the population and compound the risk of developing cancer treatment–related cardiovascular toxicity. Cardio-oncology has emerged as a new subspecialty of medicine that provides a multidisciplinary approach, bringing together oncologists, cardiologists, and allied health care providers who are tasked with optimizing the cardiovascular health of patients exposed to potentially cardiotoxic cancer therapy. Using a case-based approach, practical advice on how to identify, monitor, and treat patients with cancer who are at risk for developing cancer treatment–related cardiovascular dysfunction is discussed. Cardiovascular risk factors (e.g., age, hypertension, diabetes) and cancer therapies (chemotherapy, targeted therapy, radiation) associated with cardiovascular toxicity are presented. Current cardiac monitoring strategies such as two- and three-dimensional echocardiography, cardiac MRI, and biomarkers (troponin and brain natriuretic peptide [BNP]) are discussed. Last, the current literature on pharmacologic (e.g., angiotensin-converting enzyme inhibitors, β-blockers, statins) and lifestyle (diet and exercise) strategies to mitigate cardiovascular toxicity during and following completion of cancer therapy are reviewed.

Cardio-oncology is an emerging field tasked with identifying and treating cancer therapy related cardiac dysfunction (e.g., cytotoxic agents, immunotherapies, radiation, and hormone therapies) and optimizing the cardiovascular health of cancer patients exposed to these agents. Novel cancer therapies have led to significant improvements in clinical outcomes for breast cancer patients. In this article, we review the current literature on assessing cardiovascular risk of breast cancer therapies and discuss strategies (including pharmacological and lifestyle interventions) to prevent cardiovascular toxicity.

Breast cancer is the most common cancer in women, with 15%&ndash, 25% of those tumours overexpressing the human epidermal growth factor receptor 2 (her2), which is associated with more aggressive disease. On rare occasions, patients present with a paraneoplastic syndrome months to years before their cancer diagnosis. Paraneoplastic cerebellar degeneration (pcd) is associated with fewer than 1% of cancers and is strongly associated with breast and gynecologic malignancies. Anti-Yo antibody is the antibody most frequently identified with the syndrome, and it is associated with a very poor prognosis. Recent studies have implicated a relationship between overexpression of her2 and anti-Yo&ndash, mediated pcd. Current pcd treatments include tumour removal, chemotherapy, targeted therapy, and immune-suppressive treatments. Outcomes of pcd are typically poor, and no guidelines for treatment currently exist. Early recognition followed by rapid initiation of treatment remains the cornerstone of therapy.

Background Trastuzumab (T) and anthracycline (A)-based chemotherapy is considered the standard of care in human epidermal growth factor receptor-2+ overexpressing breast cancer, but requires monitoring for known cardiotoxicity using left ventricular (LV) ejection fraction (EF) every 3–4 months during treatment. It is not conclusively established whether diastolic dysfunction (DD) precedes LVEF decrease in patients developing trastuzumab-induced cardiotoxicity (TIC). Objective The aim was to elucidate whether DD precedes LVEF decrease in trastuzumab-treated patients being monitored with radionuclide multigated acquisition for TIC. Patients and methods Patients treated with T±A-based chemotherapy who had undergone multigated acquisition were selected by date range (January 2006–September 2015). Up to four scans were analyzed per patient: (a) pre-A therapy, (b) pre-T therapy, (c) 4 months into T therapy, and (d) at end of T therapy. Baseline referred to the first scan of each patient (i.e. pre-A or pre-T). LV systolic and DD were defined as follows: EF less than 50% or a 10-point decrease from baseline and LV peak filling rate (PFR) less than 2.5 end-diastolic volume/s and time to peak LV filling rates (TPFR) greater than 180 ms, respectively. Results A total of 202 patients were screened for this study, of whom 153 had received A therapy (5.1±4.1 months duration) before T, 192 had 4 months of follow-up data, and 146 had 4 months of follow-up data and beyond (10.5±5.0 months). LVEF decreased with A and T therapy (P0.1), nor did TPFR (P>0.3). Conclusion Patients with normal diastolic function at baseline receiving trastuzumab±anthracycline adjuvant therapy may develop DD before SD, therefore offering an opportunity for early referral to cardiologists to optimize cardiovascular risk factors and manage cardiotoxicity.

Treat ER+ight is the 1st prospective observational study in Canadian postmenopausal women with HR+ HER2– advanced breast cancer currently receiving endocrine therapy (ET) alone or in combination with targeted therapy (TT) (NCT02753686). Methods: This pre-planned interim analysis describes baseline characteristics, treatment sequence, monitoring patterns, patient-reported quality-of-life (QoL) and resource utilization of patients enrolled in ET and ET+TT cohorts within the 1st 3 months of therapy. At data cut-off (13Mar'17), 100 patients were enrolled from 24 sites since Mar'16. Results: Baseline Patient and Disease Characteristics ET (n=42)ET + TT (n=58)Median age, years (range)70 (37-88)63 (39-80)ECOG 0-1, (%)6072Median time since primary BC diagnosis, years (range)4.5 (0-37)5 (0-25)Median time with advanced BC diagnosis, years (range)1 (0-16)1 (0-7)Sites of metastases (%) Bone only3829Visceral only3338Bone + visceral2924Last prior line of therapy included but not limited to (%) Letrozole4131Anastrozole1219Tamoxifen1214Exemestane122Palbociclib+Fulvestrant07Line (L) of metastatic therapy (%) 1L19222L38433L4335 Enrollment therapy (%): everolimus+exemestane (35), fulvestrant (15), palbociclib + letrozole (15), tamoxifen (14), exemestane (7), palbociclib+fulvestrant (7), letrozole (4) and palbociclib+exemestane (1). Follow-up visits with physician after therapy initiation ET, ET+TT (%): week 2 (5, 47), month 1 (71, 67), month 3 (43, 31). Numerical differences were observed in EORTC QLQ C30 and BR23 global health status/QoL, functional and symptom scale scores between ET and ET+TT cohorts. Mean changes in transformed scores from baseline to month 3 were generally similar between cohorts however 'therapy side effects' symptom item worsened in ET+TT cohort (P = 0.031, Wilcoxon rank sum). Resource utilization in between scheduled visits during 1st 3 months of therapy was similar between cohorts for physician/radiology, hospitalizations and ER visits however patient calls to supportive care nurse was increased in ET+TT cohort (P = 0.008, Fisher's exact). Treatment discontinuation rate (20%) was similar between cohorts with progression as predominant reason for initiating next therapy. Chemotherapy (CT) was the most frequent subsequent therapy and represented 1st line metastatic CT for majority of patients. Conclusions: ET+TT patients were younger, had better ECOG, more visceral disease and 60% received everolimus+exemestane with Citation Format: Dent S, Califaretti N, Doyle C, Ferrario C, Chouinard E, Kulkarni S, Roy J-A, Perri SR, Chia S. Treat ER+ight Canadian prospective observational study in HR+ advanced breast cancer: 2nd interim analysis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-15-02.

Background: The identification of coronary artery calcification (CAC) detected coincidentally on chest CT exams could assist in cardiovascular risk assessment but may not be reported consistently on clinical studies. Cardiovascular risk factor stratification is important to predict short term cardiac events during cancer therapy and long term cardiac event free survival in cancer patients. We sought to determine the prevalence of CAC and clinical reporting rates in a cohort of cancer patients at high risk of cancer therapy related cardiac events. Methods: 408 Breast cancer patients who were referred to a cardiac oncology clinic were screened. Inclusion criteria included having had a CT chest and the absence of known coronary disease. Among those screened 263 patients were included in the study. Results: CAC was identified in 70 patients (26%). CAC was reported in 18% of studies. The reporting rates of CAC increased with the extent of coronary calcification (p

Pelareorep, a serotype 3 reovirus, has demonstrated preclinical and early clinical activity in breast cancer and synergistic cytotoxic activity with microtubule targeting agents. This multicentre, randomized, phase II trial was undertaken to evaluate the efficacy and safety of adding pelareorep to paclitaxel for patients with metastatic breast cancer (mBC). Following a safety run-in of 7 patients, 74 women with previously treated mBC were randomized either to paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 every 4 weeks plus pelareorep 3 × 1010 TCID50 intravenously on days 1, 2, 8, 9, 15, and 16 every 4 weeks (Arm A) or to paclitaxel alone (Arm B). Primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate, overall survival (OS), circulating tumour cell counts, safety, and exploratory correlative analyses. All comparisons used a two-sided test at an alpha level of 20%. Survival analyses were adjusted for prior paclitaxel. Final analysis was performed after a median follow-up of 29.5 months. Pelareorep was well tolerated. Patients in Arm A had more favourable baseline prognostic variables. Median adjusted PFS (Arm A vs B) was 3.78 mo vs 3.38 mo (HR 1.04, 80% CI 0.76–1.43, P = 0.87). There was no difference in response rate between arms (P = 0.87). Median OS (Arm A vs B) was 17.4 mo vs 10.4 mo (HR 0.65, 80% CI 0.46–0.91, P = 0.1). This first, phase II, randomized study of pelareorep and paclitaxel in previously treated mBC did not show a difference in PFS (the primary endpoint) or RR. However, there was a significantly longer OS for the combination. Further exploration of this regimen in mBC may be of interest.

Patients with breast cancer (bca) who overexpress her2 (the human epidermal growth factor receptor 2) are at risk for cardiotoxicity when treated with anthracycline-based chemotherapy and her2-targeted agents. The Framingham risk score (frs) is a validated tool that stratifies patients into high-, intermediate-, or low-risk groups and calculates their 10-year risk of developing cardiovascular disease (cvd) based on past medical history, systolic blood pressure, and measurement of serum lipids. We retrospectively analyzed patients with her2-positive bca to determine whether the frs predicts adverse cardiovascular (CV) events or cardiotoxicity in patients treated using anthracyclines or her2-targeted therapy, or both. The frs was determined for patients with bca referred to The Ottawa Hospital Cardiology&ndash, Oncology Clinic from October 2008 to August 2014. The patients were stratified into high (&ge, 20%), intermediate (10%&ndash, 20%), and low (10% to a lvef &le, 50%]. Of the 152 patients included in the analysis (median follow-up: 40.7 months, range: 3.5&ndash, 263 months), 47 (31%) were classified as high risk, 36 (24%), as intermediate risk, and 69 (45%), as low-risk. The number of cvd-related hospitalizations and deaths was 22, for an overall prevalence of 14%, with significantly more events occurring in high-risk than in low-risk patients (odds ratio: 4.18, 95% confidence limits: 1.47, 11.89). The frs predicted a 10-year risk of any cv event of 11.2% and underestimated the actual rate of cv events in the entire cohort. High frs was not associated with cardiotoxicity (p = 0.82). In a population of patients with her2-positive bca referred to a cardiology&ndash, oncology clinic, the frs does not accurately predict the risk of cv events or cardiotoxicity.

PurposeCardiac dysfunction is a serious adverse effect of certain cancer-directed therapies that can interfere with the efficacy of treatment, decrease quality of life, or impact the actual survival of the patient with cancer. The purpose of this effort was to develop recommendations for prevention and monitoring of cardiac dysfunction in survivors of adult-onset cancers.MethodsRecommendations were developed by an expert panel with multidisciplinary representation using a systematic review (1996 to 2016) of meta-analyses, randomized clinical trials, observational studies, and clinical experience. Study quality was assessed using established methods, per study design. The guideline recommendations were crafted in part using the Guidelines Into Decision Support methodology.ResultsA total of 104 studies met eligibility criteria and compose the evidentiary basis for the recommendations. The strength of the recommendations in these guidelines is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms.RecommendationsIt is important for health care providers to initiate the discussion regarding the potential for cardiac dysfunction in individuals in whom the risk is sufficiently high before beginning therapy. Certain higher risk populations of survivors of cancer may benefit from prevention and screening strategies implemented during cancer-directed therapies. Clinical suspicion for cardiac disease should be high and threshold for cardiac evaluation should be low in any survivor who has received potentially cardiotoxic therapy. For certain higher risk survivors of cancer, routine surveillance with cardiac imaging may be warranted after completion of cancer-directed therapy, so that appropriate interventions can be initiated to halt or even reverse the progression of cardiac dysfunction.