Clinicopathological characteristic of HER2 low breast cancers in the Singapore population
Puay Hoon Tan, Wong Fuh Yong, Mihir Gudi

Abstract: Overexpression of human epidermal growth factor receptor 2 (HER2) protein in breast cancers carries significant prognostic and therapeutic implications. Anti-HER2 blockade has shown to be a useful adjunct to surgery in treating HER2-positive tumours. The recently published Phase III clinical trial (DESTINY-Breast04) has demonstrated that an antibody-drug conjugate (trastuzumab-deruxtecan) significantly reduced disease progression and death in patients with metastatic disease with IHC scores 1+, or 2+ and without ISH amplification, defining a new category of cases known as HER2 low. Based on early published data, HER2 low breast cancers comprise approximately 50% of all breast cancers and they are a biologically heterogeneous group of tumours which include both hormone receptor positive luminal and the triple-negative subtypes, as well as low and high grade tumours, all of which are known to have different biological aggressiveness, molecular signatures and treatment regimes. The current HER2 immunohistochemical scoring algorithm has its limitations in categorising a tumour as HER2 low, particularly those with extremely low HER2 protein expression, current known as HER2 “ultra low”. The aim of this project is to analyse the clinicopathological characteristics of HER2 low and “ultra low” breast cancers within the Singapore population, which may support the identification of this group of tumours, in addition to immunohistochemistry and in situ hybridization techniques.


Joint Breast Cancer Registry Singapore