Abstract PS5-01-25: Long-term response Patterns in HER2-positive advanced breast cancer within the geicam/2014-03 (registem) study

Abstract Background: Breast cancer (BC) is a heterogeneous disease with distinct subtypes, each having different prognosis and treatment responses. RegistEM aims to understand the distribution of subtypes in advanced BC (ABC) and their clinical implications. Significant advances have led to better median overall survival (OS) in patients (pts) with HER2+ BC. Targeted anti-HER2 therapies have changed the management and prognosis of HER2+ ABC, although there is a lack of data from long-term responders (LTRs). Methods: ABC pts, either recurrent early BC (EBC) or de novo metastatic (dnMBC), diagnosed from Jan-16 to Dec-19, were enrolled in this ambispective non-interventional cohort study. Biological samples from primary tumors, metastatic lesions, and blood were collected. This subanalysis aims to better characterize LTRs among pts with HER2+ ABC receiving 1st-line (1L) or 2nd-line (2L) anti-HER2 targeted therapies. We defined LTR as pts who did not progress to 1L therapy for more than 35 months (mo.), or for more than 16 mo. in 2L therapy. BC subtype was assessed by immunohistochemistry (IHC) with or without in situ hybridization (ISH) in the most recent tumor sample before 1L therapy. In the current analysis, 1,900 pts from 38 GEICAM sites were included (database ongoing, cut-off date Mar 17, 2025). Results: 341/1,900 (18%) pts had HER2+ ABC, 133(39%) were considered as LTR and 197 (58%) as non-LTR (NLTR), 11 pts were excluded due to lack of information or not receiving systemic treatment for ABC. At ABC diagnosis, median age was 56 years (interquartile range 48-69), all pts were female (70% postmenopausal), 68 (51%) LTR and 77 (39%) NLTR had dnMBC (p=0.0881). Hormone receptors positive (HR+) were observed in 92 (69%) LTR and 122 (62%) NLTR. HER2 status was confirmed by IHC 3+ in 89 (67%) LTR and 140 (71%) NLTR, and ISH amplified in 55 (41%) LTR and 81 (41%) NLTR. A different pattern of metastatic spread was observed between LTR and NLTR (p