Abstract P4-07-55: Neoadjuvant trastuzumab and pertuzumab in combination with anthracyclines in HER2-positive early breast cancer: real-world data on effect of body mass index in cardiac safety
Authors: Simão Diana , Sardinha Mariana , Gil Lúcia , Montenegro Alexandra , Mendes José , Fernandes Leonor , Winckler Patrícia , Luz Ricardo , Oliveira Sónia 
Published: March 2023

Abstract
BACKGROUND: Neoadjuvant therapy with trastuzumab and pertuzumab (HP) combined with chemotherapy (ChT) is the standard of care in ≥ cT2cN0 or N+ HER2-positive early breast cancer (EBC). Although cardiotoxicity is a known adverse effect of anti HER2-therapy and anthracyclines, recently BERENICE final analysis showed cardiac safety of HP in combination with standard or dose-dense anthracycline-based ChT. However, real-world data is lacking, specifically in patients (pts) with identified cardiovascular (cv) risk factors. Our study aimed to evaluate cardiac safety of HP and anthracyclines in HER2+ EBC and explore potential impact of body mass index (BMI). METHODS: This retrospective analysis included HER2+ EBC pts receiving neoadjuvant HP and anthracycline- and taxane- based ChT, at our institution, between 2016 and 2021. Baseline clinical, demographic, histopathological and immunohistochemical features were reported. Pts were categorized as underweight (&lt; 18.5kg/m2), normal (≥18.5;&lt; 25kg/m2), overweight (≥25;&lt; 30kg/m2) and obese (≥30kg/m2), according to basal BMI WHO categories. The primary objective was to evaluate cardiac safety, assessed by incidence of left ventricular ejection fraction (LVEF) declines (≥10% from baseline and to a value &lt; 50%) and NYHA class III/IV heart failure. Univariate and multivariate logistic regression analysis were performed using BMI as a categorical variable. Safety data were compared in subgroup analyses for underweight/normal and overweight/obese pts. Statistics were performed with IBM™ SPSS software, version 23. RESULTS: Our analysis enrolled 112 female pts, with a median age of 54 years (30-78), including 22pts (19.6%) with ≥65years and 55 (49.1%) postmenopausal women. Most pts (n=89; 79.5%) had HR-positive disease. 44pts (39.3%) had stage II and 68pts (60.7%) had stage III disease. According to BMI, pts were classified as underweight (n=3; 2.7%), normal (n=40; 35.7%), overweight (n=47; 42%) and obese (n=22; 19.6%). No association was found between BMI and tumor stage (p=0.829), grade (p=0.753) and HR status (p=0.212). Other baseline cv risk factors were identified: former/active smoker (n=34;30.4%), diabetes (n=10;8.9%), hypertension (n=30;26.8%), and dyslipidemia (n=32;28.6%). Most pts had ≥2 cv risk factors (n=66;58.9%). Two diferent regimes were used FEC100-D+HP (2016-2019, n=84) and ddAC-wkPaclitaxel+HP (2020-2021, n=28). Overall, pCR was achieved in 62 pts (55.4%). Regarding cardiac safety evaluation, 4 pts (3.6%) experienced at least one LVEF decline ≥10% from baseline and to a value &lt; 50%, including 3 pts that were overweight/obese. Declines were reversible in all pts, with recovery by next assessment. Two pts (1.8%) experienced one NYHA class III heart failure event. Both pts were overweight/obese and had another concomitant risk factor for cardiovascular disease. Both pts discontinued treatment. No statistically significant association was found between overweight/obesity and cardiac events (OR 1.26, 95%CI 0.22-7.20; p=0.792). Median follow-up duration was 39 months. No new safety signals were identified. CONCLUSION: Cardiac safety of neoadjuvant HP in combination with anthracyclines in HER2-positive EBC in our real-world data is consistent with previous studies. Despite most cardiac events occurred in overweight/obese pts, no statistically significant effect was found. Further studies are needed to evaluate cardiotoxicity in pts with cv risk factors and evaluate impact of therapeutic interventions.
Citation Format: Diana Simão, Mariana Sardinha, Lúcia Gil, Alexandra Montenegro, José Mendes, Leonor Fernandes, Patrícia Winckler, Ricardo Luz, Sónia Oliveira. Neoadjuvant trastuzumab and pertuzumab in combination with anthracyclines in HER2-positive early breast cancer: real-world data on effect of body mass index in cardiac safety [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-55.