HER2-low breast carcinoma: A newly recognised entity driving paradigm shifts in precision treatment

Recent clinical trials have shown the usefulness of anti-HER2 (Human epidermal growth factor receptor 2) treatment in the newly described "HER2-low" subset of breast carcinoma, offering added treatment option to the once considered non-responders. This study aimed to identify this important new subset's demographic and pathological features in a Malaysian cohort.

All newly and recurrent histopathologically-diagnosed invasive breast carcinomas encountered at the University of Malaya Medical Centre (UMMC) between January 2018 to December 2023 that satisfied inclusion criteria were enrolled. Patient demographics were retrieved from the histopathological requests. All haematoxylin and eosin (H&E) stained, immunohistochemically (IHC) stained HER2, oestrogen receptor (ER) and progesterone receptor (PR) together with HER2 amplification assayed by dual-colour dual-hapten in situ hybridisation (DDISH) sections for all cases were reviewed for histological type, histological grade, pathological stage, hormone receptors (HR encompassing ER and PR) and HER2 status.

710 invasive breast carcinomas were finally included. HER2-low was noted in 48.2% (n = 342) of the carcinomas, while 191 (26.9%) were in the conventional HER2 positive category. HER2-low carcinomas demonstrated significantly lower (Grade 1 and 2) histological grade and were more commonly hormone status positive compared with both HER2 positive and negative groups.

HER2-low constituted a significant number of breast carcinomas and appears to have its own unique features. The recognition of this category has expanded anti-HER2 treatment options to an additional 48% of breast carcinomas.