Chemotherapy Use, Healthcare Resource Utilisation, and Direct Costs in High-Risk Early-Stage ER+/HER2– Breast Cancer in Italy: A Real-World Study Linking Administrative and Pathology Data

Background/Objectives: Patients with high-risk early-stage oestrogen receptor-positive/human epidermal growth factor receptor 2-negative early breast cancer (ER+/HER2– eBC) remain at high risk of recurrence despite standard endocrine therapy. Given the limited real-world data in Italy, this analysis evaluated treatments, economic burden and clinical outcomes in routine practice. Methods: Administrative healthcare databases linked with pathology data were used to identify patients with ER+/HER2– eBC undergoing surgery. The overall population (Cohort #1) comprised patients identified between January 2010 and June 2024. A subset meeting high-risk criteria constituted Cohort #2 (Grade 3 tumours AND clinical stage T1c–T2/N1–N2 or T3–T4/N0–N2; when TNM components were unavailable, clinical stage II–III patients were included). Healthcare resource utilisation and direct costs were assessed during neoadjuvant, adjuvant, and follow-up phases. Recurrence rate, real-world event-free survival and overall survival were evaluated during the 4 years post-surgery using Kaplan–Meier curves. Results: Among 17,731 patients identified as ER+/HER2– eBC (Cohort #1), 366 were classified as high-risk (Cohort #2). The descriptive analysis documented substantial healthcare resource utilisation and direct costs in the high-risk subgroup during both neoadjuvant and adjuvant phases, together with a considerable recurrence burden and reduced survival probabilities. Conclusions: This descriptive real-world analysis provides estimates of the clinical and economic burden of ER+/HER2– eBC in the real Italian practice, with a focus on the high-risk subgroup. Post-surgery cost estimates reflect healthcare expenditure during recurrence-free follow-up and do not capture the costs of recurrent or metastatic disease. These findings highlight the healthcare resources required for the management of high-risk eBC and the need for continued efforts to improve clinical outcomes.