1092 Background: Endocrine sensitivity/resistance (ES/ER) is a key prognostic and predictive factor in patients (pts) with Hormone Receptor-positive, Human Epidermal growth factor Receptor 2-negative advanced Breast Cancer (HR+/HER2- aBC). Cyclin Dependent Kinase 4/6 inhibitors (CDK4/6i)+Endocrine Therapy (ET) are standard 1 st line therapy for HR+/HER2- aBC pts regardless of tumor ES/ER status at diagnosis. However, the prognostic value of tumor recurrence dynamics within ES/ER groups has never been investigated. Methods: We conducted a pre-planned analysis of the multicenter, real-world, Italian study PALMARES-2 (NCT06805812) to evaluate the prognostic role of tumor recurrence dynamics, de novo aBC presentation and distant recurrence-free interval (DFRI) in pts with HR+/HER2- aBC treated with 1 st line ET+CDK4/6i between January 2016 and September 2024. DRFI was defined as the time from surgery to the detection of aBC. The primary endpoint was real-world progression-free survival (rwPFS), defined as the time between ET+CDK4/6i initiation and disease progression (PD) or patient death. Results were adjusted through Multivariable Cox regression for 16 relevant covariates. Results: Of 4,234 pts enrolled, 2,858 (67.5%) had ES and 1,376 (32.5%) had ER disease at aBC diagnosis. Median follow-up was 38.6 and 42.7 months, respectively. After adjustment, ER was associated with poorer rwPFS compared to ES (adjusted hazard ratio aHR 1.78, 95% CI 1.60-1.96). In the ER cohort, secondary tumor resistance with recurrence during years (y) 3-5 of adjuvant (adj) ET or 10 y from adj ET end had significantly longer rwPFS when compared to pts recurring 10 y from adj ET end 275 45.2 0.30 (0.23-0.40) De novo aBC 1422 31.3 0.50 (0.42-0.59)
Vernieri et al. (2026) studied this question.