Geneviève Boileau-Jolimoy, Anne-Laure Martin, Thierry Petit, Patrick Arveux, Elisé G. Kaboré, Paul Cottu, Johanna Wassermann, A. Lesur, Florence Dalenc, Ines Vaz-Luis, Charles Guenancia, Mahmoud Ibrahim, Olivier Arsene, Fabrice Andre, Jérôme Lemonnier, Barbara Pistilli, Charles Coutant, Antonio Di Meglio, Antoine Arnaud, Philippe Rouanet, 'Health across Generations' Team [Villejuif], Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Cardiologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Gustave Roussy (IGR), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Institut Curie [Paris], Centre Alexis Vautrin [Vandoeuvre-lès-Nancy], Centre Paul Strauss, CRLCC Paul Strauss, Institut Claudius Regaud, Institut du Cancer de Montpellier (ICM), Institut Sainte Catherine [Avignon], Centre Hospitalier de Blois (CH Blois), Centre Hospitalier Régional d'Orléans (CHRO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Polyclinique du Parc - Clinique Drevon [Dijon], Unicancer [Paris], This research was supported by the French Government under the 'Investment for the Future' program managed by the National Research Agency (ANR), grant n˚ ANR-10-COHO-0004 (FA) and by a Clinical Research Fellowship from the French government (EGK)., ANR-10-COHO-0004,CANTO,Etude des toxicités chroniques des traitements anticancéreux chez les patientes porteuses cancer(2010), Bodescot, Myriam, Cohortes - Etude des toxicités chroniques des traitements anticancéreux chez les patientes porteuses cancer - - CANTO2010 - ANR-10-COHO-0004 - COHO - VALID, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), and Centre Hospitalier de Blois (CHB)
Background 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., Charles Guenancia and colleagues investigate the association of obesity to breast cancer treatment related cardiotoxicity., Author summary Why was this study done? Anthracyclines remain a cornerstone of breast cancer therapy, in combination with new-generation targeted drugs such as trastuzumab, and represent the major culprit in chemotherapy-induced heart disease. In a recent meta-analysis, we showed that overweight and obesity increased cardiotoxicity, but it was not possible to take into account associated cardiac risk factors or other classic risk factors for anthracycline and trastuzumab cardiotoxicity. We examined the association of body mass index (BMI) and cardiotoxicity using prospective data collected in the CANTO study, a French national cohort. What did the researchers do and find? In patients treated for stage I–III breast cancer with anthracyclines and/or trastuzumab, being obese was associated with increased risk of developing cardiotoxicity, regardless of other predictors of cardiotoxicity. Among all the classic risk factors for cardiotoxicity, overweight and obesity were by far the most common risk factors in this breast cancer population. What do these findings mean? Obesity appears to be a risk factor for cardiotoxicity in breast cancer patients. Overweight and obese patients may benefit from careful cardiac screening and follow-up during and after chemotherapy.