Dissecting the prognostic role of baseline body mass index (BMI) in early breast cancer (BC): Individual patient-level analysis from five Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) randomized clinical trials (RCTs).

person Davide Soldato IRCCS Ospedale Policlinico San Martino, Università degli Studi di Genova, Genova, Italy info_outline Davide Soldato, Eva Blondeaux, Marco Bruzzone, Silvia Mura, Michelino De Laurentiis, Anna Turletti, Sabino De Placido, Giancarlo Bisagni, Anita Rimanti, Andrea Michelotti, Alessandra Fabi, Antonio Russo, Stefania Gori, Antonio Durando, Guilherme Nader Marta, Evandro de Azambuja, Antonio Di Meglio, Ines Vaz-Luis, Matteo Lambertini, Lucia Del Mastro

Authors person Davide Soldato IRCCS Ospedale Policlinico San Martino, Università degli Studi di Genova, Genova, Italy info_outline Davide Soldato, Eva Blondeaux, Marco Bruzzone, Silvia Mura, Michelino De Laurentiis, Anna Turletti, Sabino De Placido, Giancarlo Bisagni, Anita Rimanti, Andrea Michelotti, Alessandra Fabi, Antonio Russo, Stefania Gori, Antonio Durando, Guilherme Nader Marta, Evandro de Azambuja, Antonio Di Meglio, Ines Vaz-Luis, Matteo Lambertini, Lucia Del Mastro Organizations IRCCS Ospedale Policlinico San Martino, Università degli Studi di Genova, Genova, Italy, Unit of Clinical Epidemiology, Ospedale Policlinico San Martino, Genova, Italy, Genoa, Italy, Unit of Clinical Epidemiology, Ospedale Policlinico San Martino, Genova, Italy, Department of Medical Oncology, UOC Oncologia Medica, University Hospital of Sassari, Sassari, Italy, Sassari, Italy, IRCCS Fondazione G. Pascale, Naples, Italy, Medical Oncology, Ospedale Martini ASL Città di Torino, Torino, Italy, Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy, Naples, Italy, Medical Oncology Unit, Clinical Cancer Centre, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy, Reggio Emilia, RE, Italy, Azienda Ospedaliera di Mantova, Mantova, Italy, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy, Precision medicine in senology Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy, Università di Palermo, Palermo, Italy, IRCCS SACRO CUORE DON CALABRIA, Negrar Di Valpolicella, Italy, Breast Unit, Città della Salute e della Scienza, ASO S.Anna, Torino, Italy, Academic Trials Promoting Team, Institut Jules Bordet and l’Université Libre de Bruxelles (U.L.B), Brussels, Belgium, Cancer Survivorship Group, INSERM Unit 981, Gustave Roussy, Villejuif, France, Breast Cancer Survivorship Group, INSERM Unit 981, Gustave Roussy, Villejuif, France Abstract Disclosures Research Funding Other “Associazione Italiana per la Ricerca sul Cancro”, AIRC (MFAG 2020 ID 24698) Background: Nearly half of patients (pts) are overweight or obese at BC diagnosis (dx). Higher BMI at dx has been associated with cardiometabolic comorbidities, higher risk of severe treatment-related sequelae, and worse quality of life. Previous studies showed inferior survival outcomes among patients with early BC and high BMI, although not consistently. The aim of this study was to explore the prognostic role of BMI at dx using data from five RCTs of adjuvant therapy for early stage BC with long-term follow-up. Methods: Pts with known BMI at dx, randomized in the MIG-1, MIG-5, GIM-2, GIM-3 and GIM-6 phase III RCTs were included. BMI was categorized as lean ( < 25 kg/m2), overweight (25-30 kg/m2) or obese (≥ 30 kg/m2). Outcomes included disease-free survival (DFS), breast cancer free-interval (BCFI) and overall survival (OS). Survival estimates were compared using the Kaplan-Meier method and log-rank test. Multivariable Cox proportional hazard models stratified by trial and relevant prognostic factors assessed associations between BMI and outcomes. Results: Among 7334 pts in the overall population, mean age was 56.4 years (SD 11.2), 67.8% had node-positive disease, 76.9% received chemotherapy and 83.0% endocrine therapy. Most pts were overweight (33.1%) or obese (21.0%) and 45.9% were lean. Higher BMI was associated with older age, larger tumor size, higher nodal status, and HR+/HER2- subtype. At a median follow-up of 10.0 years (IQR 6.1-15.1) there were 2165 DFS, 1674 BCFI and 1354 OS events. Pts with higher BMI had worse DFS and OS (log-rank p = 0.007 and p < .0001, respectively), but similar BCFI (p = 0.48). BMI at dx was an independent risk factor for worse OS, but not for DFS and BCFI (Table). Results in the HR+/HER2- population (n = 4093) were consistent: pts with higher BMI had worse DFS, BCFI, and OS (log-rank p = 0.001, p < .006, and p < .0001, respectively) and BMI at dx was an independent risk factor only for worse OS (aHR [95%CI] 1.06 [0.84-1.32] and 1.31 [1.02-1.67] for overweight and obese vs lean pts, respectively). Conclusions: In this large study of pts with early BC treated in RCTs with long-term follow-up, higher BMI at dx was an independent risk factor for overall mortality but not for BC-specific outcomes. Weight loss interventions may mitigate the detrimental effect of excess body weight on outcomes of BC survivors, including by reducing the burden and risks of associated cardiometabolic comorbidities. DFS, 10y rate aHR BCFI, 10y rate aHR OS, 10y rate aHR Lean 71.8 (70.1-73.4) Ref 76.7 (75.1-78.2) Ref 83.1 (81.6-84.4) Ref Overweight 69.3 (67.1-71.4) 1.01 (0.90-1.12) 75.7 (73.6-77.6) 0.96 (0.85-1.08) 80.0% (78.0-81.8) 1.06 (0.92 – 1.21) Obese 67.7 (64.7-70.5) 1.08 (0.96-1.23) 74.3 (71.5-76.8) 1.04 (0.90-1.20) 79.7% (77.0-82.1) 1.22 (1.04 – 1.43) Parentheses show 95%CIs