Abstract PO4-19-12: Trial in progress: An Observational Study to Examine Changes in Metabolic Syndrome Components in Patients With Breast Cancer Receiving (Neo)Adjuvant Aromatase Inhibitors
Authors: LeVee Alexis , Ruel Nora , Seewaldt Victoria , Mortimer Joanne 
Published: May 2024

Abstract
Background: (Neo) adjuvant systemic therapy has been shown to adversely impact metabolic health manifested as weight gain, dyslipidemia, and insulin resistance, which ultimately lead to the development of metabolic syndrome (MetS). MetS increases the risk of development for type 2 diabetes mellitus and cardiovascular disease and is associated with an increased risk of breast cancer recurrence, death due to breast cancer, and all-cause mortality. We have previously reported that 76% of metabolically healthy women receiving (neo) adjuvant chemotherapy will develop MetS at a median of 15 weeks. The impact of aromatase inhibitors (AIs) on metabolic health has not been systematically assessed in a longitudinal study. We hypothesize that AIs in the (neo) adjuvant setting will alter metabolic parameters and have embarked on a clinical trial to study this.
Methods: This is a prospective observational study that will include: postmenopausal patients with newly diagnosed, early-stage hormone receptor (HR)-positive breast cancer with planned (neo)adjuvant treatment with an AI. Participants will be excluded if they have received or have planned treatment with (neo)adjuvant chemotherapy or are currently receiving antidiabetic medications or cholesterol-lowering agents. All patients will undergo a baseline assessment that includes: BMI, physical exam inclusive of blood pressure, waist circumference, assessment of body fat, lipid profile, insulin, metabolic biomarkers, and completion of the Functional Assessment of Cancer Therapy – Endocrine Symptoms (FACT-ES). Following institution of an AI, reassessment of the aforementioned tests will be repeated after 4 months and 12 months of therapy. The primary endpoint is the change in insulin resistance (as measured by HOMA-IR, homeostatic model assessment for insulin resistance) at 4 months. Secondary endpoints include the change in HOMA-IR at 12 months and the change in individual MetS components, metabolic biomarkers, anthropometric measurements, as well as FACT-ES scores from baseline to 4- and 12-months of AI treatment. The mean paired differences will be calculated for HOMA-IR measurements as well as for the secondary endpoints, and the 1-sided paired t-test will be used to test for statistical significance. One-way analysis of covariance will be used to compare means while adjusting for age, race/ethnicity, and BMI. Using a 1-sided paired t-test for the mean difference in HOMA-IR measurements from baseline to 4 months, we will have 80% power to detect an effect size of 0.405 with 40 patients (α = 0.05). Enrollment began in April 2023 and is ongoing. Contact alevee@coh.org for more information. Given the increased recognition of the importance of metabolic health in breast cancer outcomes, this data will inform future trials that focus on maintaining metabolic health in breast cancer survivors.
Citation Format: Alexis LeVee, Nora Ruel, Victoria Seewaldt, Joanne Mortimer. Trial in progress: An Observational Study to Examine Changes in Metabolic Syndrome Components in Patients With Breast Cancer Receiving (Neo)Adjuvant Aromatase Inhibitors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-12.