Risque d'évènements cardiovasculaires chez les survivantes de cancer du sein : étude des facteurs prédictifs, cohortes CANTO et E3N

Cardiovascular disease and breast cancer (BC) are the most frequent chronic conditions in women, and they share several risk factors that could modify treatment regimens and toxicity of chemotherapy, subsequently negatively affecting the prognosis.In this doctoral project, we aimed at 1) studying the association of overweight and obesity, and the risk of cardiotoxicity after chemotherapy in the CANTO cohort, 2) performing a systematic review of the literature of prognostic models developed to predict chemotherapy-related cardiotoxicity in BC survivors, and 3) studying in the E3N cohort, firstly the incidence of CV risk factors and their association in women with or without BC and, secondly, in BC survivors, comparing the occurrence of major adverse cardiovascular events (MACE) according to cardiovascular risk factors and BC characteristics.To achieve our objectives, we used data from the CANTO cohort including 5,801 French women with localized BC (intermediate analysis at M12), data from the French E3N cohort including 98,995 women since 1990, and data from literature search on prognostic models developed to predict chemotherapy-related cardiotoxicity in BC survivors.Our results have highlighted traditional CV risk factors (overweight/obesity, hypertension, type 2 diabetes), clinical and histological factors (stage, grade), and biomarkers (ER, PR, HER2) as predictive factors of cardiotoxicity and MACE. Our results reveal that overweight and obesity are frequent risk factors for cardiotoxicity in BC survivors. Obese women had an increased risk of cardiotoxicity compared to normal-weight women after regimens of anthracycline and/or trastuzumab. We have also highlighted the role that overweight/obesity plays on the increased risk of BC but also as a pejorative factor in BC survivors. This information, of prognostic value in clinical practice, represents the first step towards personalized treatment for each patient newly diagnosed with BC.Although substantial progress has been made in the identification of prognostic and predictive factors for the risk of cancer treatment-related cardiovascular toxicities, we are not yet able to accurately predict which patients are likely to develop cardiotoxicity.Les maladies cardiovasculaires et le cancer du sein (CS) sont les pathologies chroniques les plus fréquentes chez la femme et partagent en commun un certain nombre de facteurs de risque qui pourraient modifier les schémas thérapeutiques et la toxicité de la chimiothérapie, affectant par la suite négativement le pronostic.Les objectifs de ce projet doctoral étaient d'étudier l'influence du surpoids et de l'obésité sur le risque de cardiotoxicité après traitement par chimiothérapie dans la cohorte CANTO, de réaliser une revue systématique de la littérature des modèles pronostiques développés pour prédire la cardiotoxicité liée au traitement par chimiothérapie chez les survivantes d'un CS et d'étudier dans la cohorte E3N la présence des facteurs de risque CV et leur association chez les femmes ayant un CS ou non dans un premier temps et dans un second temps, chez les survivantes de CS, de comparer la survenue d'évènements cardiovasculaires majeurs (MACE) en fonction des FRCV et des caractéristiques du CS.Pour se faire nous nous sommes basés sur le premier gel de la base de données de la cohorte CANTO incluant 5 801 femmes françaises atteintes d'un cancer du sein localisé (analyse intermédiaire à M12), les données de la cohorte E3N suivant 98 995 femmes françaises depuis 1990, et les données de la littérature sur les modèles pronostiques développés pour prédire la cardiotoxicité liée au traitement par chimiothérapie chez les survivantes d'un CS.Nos résultats ont permis de mettre en exergue des facteurs de risque CV traditionnels (surpoids/obésité, HTA, diabète de type 2), histologiques (stade, grade), cliniques et des biomarqueurs (RE, PR, HER2) comme des facteurs prédictifs de cardiotoxicité et d'événements cardiovasculaires majeurs. Nos résultats suggèrent que le surpoids et l'obésité sont des facteurs de risque fréquents de cardiotoxicité chez les survivantes de CS. Les femmes obèses avaient une augmentation du risque de cardiotoxicité par rapport aux femmes de poids normal après traitement par anthracycline et/ou trastuzumab. Nous avons également mis en relief le rôle que joue le surpoids/obésité sur l'augmentation du risque de CS mais aussi en tant que facteur péjoratif chez les survivantes d'un CS. Ces informations, d'une valeur pronostique en pratique clinique, représentent la première étape vers un traitement personnalisé pour chaque patiente nouvellement diagnostiquée d'un CS.Bien que des progrès substantiels aient été réalisés dans l'identification de facteurs pronostiques et prédictifs pour le risque de toxicité cardiovasculaire, nous ne sommes pas encore en mesure de prédire avec précision les patientes susceptibles de développer une toxicité cardiovasculaire après traitement antinéoplasique

Risk Prediction Models for Cardiotoxicity of Chemotherapy among Patients with Breast Cancer: A Systematic Review

International audienceImportance: Cardiotoxicity is a serious adverse effect that can occur in women undergoing treatment for breast cancer. Identifying patients who will develop cardiotoxicity remains challenging. Objective: To identify, describe, and evaluate all prognostic models developed to predict cardiotoxicity following treatment in women with breast cancer. Evidence Review: This systematic review searched the Medline, Embase, and Cochrane databases up to September 22, 2021, to include studies developing or validating a prediction model for cardiotoxicity in women with breast cancer. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to assess both the risk of bias and the applicability of the prediction modeling studies. Transparency reporting was assessed with the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) tool. Findings: After screening 590 publications, we identified 7 prognostic model studies for this review. Six were model development studies and 1 was an external validation study. Outcomes included occurrence of cardiac dysfunction (echocardiographic parameters), heart failure, and composite clinical outcomes. Model discrimination, measured by the area under receiver operating curves or C statistic, ranged from 0.70 (95% IC, 0.62-0.77) to 0.87 (95% IC, 0.77-0.96). The most common predictors identified in final prediction models included age, baseline left ventricular ejection fraction, hypertension, and diabetes. Four of the developed models were deemed to be at high risk of bias due to analysis concerns, particularly for sample size, handling of missing data, and not presenting appropriate performance statistics. None of the included studies examined the clinical utility of the developed model. All studies met more than 80% of the items in TRIPOD checklist. Conclusions and Relevance: In this systematic review of the 6 predictive models identified, only 1 had undergone external validation. Most of the studies were assessed as being at high overall risk of bias. Application of the reporting guidelines may help future research and improve the reproducibility and applicability of prediction models for cardiotoxicity following breast cancer treatment

Spectrum of heart failure in sub-Saharan Africa: data from a tertiary hospital-based registry in the eastern center of Burkina Faso

Introduction: heart failure (HF) is a strong contributor to non-communicable diseases burden in sub-Saharan Africa (SSA). Few studies have addressed the pattern of HF in Burkina Faso. Methods: we conducted a prospective cohort study in patients with acute HF in the Regional Hospital Center of Tenkodogo, eastern region of Burkina Faso. Patients were consecutively enrolled from 1stJanuary 2015 to 31st December 2016 and followed up until June 2017. Primary outcome of interest was mortality. Results: overall 318 of 1805 cardiac cases presented with acute HF (17.62 %). Of the 298 patients included in the analysis process, 239 had de novo HF and 150 were male. The mean age was 58.56 ± 18.54 years. Eighty-eight patients presented with atrial fibrillation. The mean left ventricular ejection fraction (LVEF) was 38.20 ± 12.85 % with reduced ejection fraction (LVEF < 40%) accounting for 59.73% of the cases. Most of the study patients lived in rural areas. Hypertensive heart disease (50.34%) and idiopathic dilated cardiomyopathy (19.80%) were the leading causes of HF. Most patients received renin-angiotensin system blockers contrasting with a lower prescription rate of beta-blockers (99% versus 18.79% respectively). The incidence of all-cause mortality was 31 percent patients-years. Conclusion: heart failure is frequent in SSA, affecting patients at younger age. Predominantly of non-ischemic cause, commonly hypertensive, the disease is associated with high mortality

Association of body mass index and cardiotoxicity related to anthracyclines and trastuzumab in early breast cancer: French CANTO cohort study

International audienceBACKGROUND:In patients treated with cardiotoxic chemotherapies, the presence of cardiovascular risk factors and previous cardiac disease have been strongly correlated to the onset of cardiotoxicity. The influence of overweight and obesity as risk factors in the development of treatment-related cardiotoxicity in breast cancer (BC) was recently suggested. However, due to meta-analysis design, it was not possible to take into account associated cardiac risk factors or other classic risk factors for anthracycline (antineoplastic antibiotic) and trastuzumab (monoclonal antibody) cardiotoxicity.METHODS AND FINDINGS:Using prospective data collected from 2012-2014 in the French national multicenter prospective CANTO (CANcer TOxicities) study of 26 French cancer centers, we aimed to examine the association of body mass index (BMI) and cardiotoxicity (defined as a reduction in left ventricular ejection fraction [LVEF] > 10 percentage points from baseline to LVEF < 50%). In total, 929 patients with stage I-III BC (mean age 52 ± 11 years, mean BMI 25.6 ± 5.1 kg/m2, 42% with 1 or more cardiovascular risk factors) treated with anthracycline (86% epirubicin, 7% doxorubicin) and/or trastuzumab (36%), with LVEF measurement at baseline and at least 1 assessment post-chemotherapy were eligible in this interim analysis. We analyzed associations between BMI and cardiotoxicity using multivariate logistic regression. At baseline, nearly 50% of the study population was overweight or obese. During a mean follow-up of 22 ± 2 months following treatment completion, cardiotoxicity occurred in 29 patients (3.2%). The obese group was more prone to cardiotoxicity than the normal-weight group (9/171 versus 8/466; p = 0.01). In multivariate analysis, obesity (odds ratio [OR] 3.02; 95% CI 1.10-8.25; p = 0.03) and administration of trastuzumab (OR 12.12; 95% CI 3.6-40.4; p < 0.001) were independently associated with cardiotoxicity. Selection bias and relatively short follow-up are potential limitations of this national multicenter observational cohort.CONCLUSIONS:In BC patients, obesity appears to be associated with an important increase in risk-related cardiotoxicity (CANTO, ClinicalTrials.gov registry ID: NCT01993498).TRIAL REGISTRATION:ClinicalTrials.gov NCT01993498