Abstract PO3-16-04: Distribution of intrinsic subtypes in endocrine-resistant and endocrine-sensitive breast cancer

Abstract Background Breast cancer (BC) is a heterogeneous disease that can be divided into intrinsic molecular subtypes. Among the four intrinsic subtypes, Luminal A and Luminal B are the most common and associated with the best outcome, whereas HER2-enriched and basal-like are less frequent. Tumors that are estrogen receptor α (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative (ER+/HER2-) are mostly found among the luminal subtypes. Despite that patients with ER+/HER2- tumors are offered adjuvant endocrine therapy, around one-third eventually develop endocrine resistance. The aim of this study was to explore the distribution of intrinsic subtypes in endocrine-resistant primary and relapse tumors, comparing these to endocrine-sensitive controls. Materials and methods Verified endocrine-resistant BC patients diagnosed in 2008-2012 were retrospectively collected at the Karolinska University Hospital, Stockholm, Sweden. Cases (N=70) were identified as patients with ER+/HER2- primary tumors and subsequent ER+/HER2- relapse tumors within 5 years and during endocrine therapy. Patients with primary ER+/HER2- tumors without progression or relapse at 10 years of follow-up were defined as controls (N=78), diagnosed in 2005-2006. Extracted RNA from formalin-fixed paraffin-embedded tumor tissue was analyzed by Affymetrix Clariom D Microarray and assessed by Transcriptome Analysis Console and R software. Results Among the controls, the distribution of Luminal A, Luminal B, and HER2-enriched subtypes was 65.4%, 34.6%, and 0%, respectively. In primary tumors, the distribution was in turn 55.4%, 43.1%, and 1.5%, and among relapse tumors 57.6%, 37.9%, and 4.5%, respectively. A total of 19 cases, accounting for 27.1%, switched intrinsic subtypes between the paired primary and relapse tumors. No tumors exhibited the basal-like subtype. Conclusion In this unique cohort, Luminal B and HER2-enriched subtypes were more common in primary and relapse tumors of verified endocrine-resistant patients than in primary tumors of endocrine-sensitive controls. Further, the HER2-enriched subtype, although sparse, was more frequently found in patients’ relapse tumors than in their corresponding primary tumors, and over one-fourth of cases switched subtypes during progression. These findings support the presence of subtype shifting in endocrine-resistant relapses and that endocrine-resistant tumors are more prone to be of Luminal B or HER2-enriched subtypes than endocrine-sensitive tumors. Citation Format: Caroline Schagerholm, Stephanie Robertson, Emelie Karlsson, Emmanouil Sifakis, Johan Hartman. Distribution of intrinsic subtypes in endocrine-resistant and endocrine-sensitive breast cancer 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 PO3-16-04.