Exploring the Impact of Initiating Endocrine Therapy on Metabolic Health in Early Breast Cancer: Protocol for the Prospective Follow-up EMETA-study (Preprint)

BACKGROUND Adjuvant endocrine therapy is a cornerstone in managing oestrogen receptor–positive early breast cancer but may adversely affect metabolic health, such as weight gain, insulin resistance, and dyslipidaemia. These changes increase both the risk of cardiovascular disease and cancer recurrence, yet the onset and degree of metabolic deterioration following endocrine treatment initiation are not well understood. Conventional definitions like metabolic syndrome offer limited sensitivity, causing the need for more refined methods to detect and monitor subtle changes in metabolic health. OBJECTIVE This prospective follow-up study aims to investigate the impact of initiating adjuvant endocrine therapy on metabolic health in women with oestrogen receptor–positive early breast cancer. In addition, the study seeks to evaluate different approaches to classify metabolic health to better understand the clinical relevance in this population. METHODS This single-centre, prospective study enrolled 112 women with early-stage oestrogen receptor–positive breast cancer who initiated adjuvant endocrine therapy between November 2024 and April 2025. Eligible participants were aged ≥18 years with no history of diabetes. Baseline and 3-month follow-up metabolic health assessments included biometric measurements (waist/hip circumference, waist-to-hip ratio, weight, blood pressure) and non-fasting blood samples (glucose, HbA1c, lipid profile, estradiol). Metabolic health was assessed using standard metabolic syndrome (MetS) criteria, defined as meeting ≥3 of the following: blood pressure ≥130/85 mmHg, triglycerides >2 mmol/L, HDL cholesterol 88 cm, and plasma glucose >7.8 mmol/L. An Extended MetS definition included additional parameters: LDL cholesterol >3 mmol/L, BMI ≥30 kg/m², waist-to-hip ratio >0.85, and HbA1c ≥42 mmol/mol. To capture continuous variation, both definitions were evaluated as standardized Z-scores. The Metabolic Syndrome Z (MetS-Z) score was derived from the standard MetS components. The Extended Metabolic Syndrome Z score (EMETA score)—a study-specific composite Z-score—was calculated using the same method but based on the Extended MetS components. Primary outcomes were the mean change in BMI and MetS-Z score from baseline to 3 months. Secondary outcomes included changes in MetS prevalence, comparisons between MetS and Extended MetS prevalence, mean change in EMETA score, and changes in individual metabolic parameters. RESULTS Out of 166 patients screened eligible for study participation, 112 were enrolled between November 2024 and April 2025. Of the 54 not enrolled, 18 declined participation, 26 were not informed of the study by their practitioner, and 10 chose not to initiate adjuvant endocrine therapy. Follow-up is expected to be completed by mid-August 2025. CONCLUSIONS This study will offer insights into early metabolic changes following the initiation of adjuvant endocrine therapy and evaluate different approaches to classifying metabolic health. The findings may help identify patients at increased risk of cardiometabolic complications and adverse breast cancer outcomes, warranting confirmation in larger cohorts. CLINICALTRIAL Clinicaltrials.gov NCT06623903; https://clinicaltrials.gov/study/NCT06623903