An improved scoring method for human epidermal growth factor receptor-2 immunohistochemical staining in breast cancer

Anti-human epidermal growth factor receptor-2 (HER2) antibody-drug conjugates (ADCs) have shown substantial clinical therapeutic benefits for HER2-positive breast cancer (BC). Nevertheless, current HER2 scoring methods are insufficient in effectively guiding the application of ADCs. We proposed an improved HER2 scoring method to optimize the treatment strategy for ADCs in BC.

This retrospective cross-sectional clinicopathologic study introduces an improved HER2 scoring method that categorizes HER2 immunohistochemistry (IHC) staining into five levels: 0, 0+, 1+, 2+, and 3+. Specifically, (I) HER2 IHC 0 indicates no perceptible staining; (II) HER2 IHC 0+ any degree of cytoplasmic staining, or barely perceptible or incomplete membrane staining in ≤10% of tumor cells; (III) HER2 IHC 1+ refers to faint, barely perceptible or incomplete membrane staining in >10% of tumor cells; (IV) HER2 IHC 2+ represents weak-to-moderate complete membrane staining in >10% of tumor cells; and (V) HER2 IHC 3+ signifies intense, complete circumferential membrane staining in >10% of tumor cells. Among these categories, HER2 IHC 0 is interpreted as HER2-negative, HER2 IHC 0+ as HER2 ultra-low expression, HER2 IHC 1+ and 2+ (with or without HER2 gene amplification) as HER2 low expression, and HER2 IHC 3+ as HER2-positive. Meanwhile, a total of 1,448 paraffin-embedded specimens were subjected to IHC staining for estrogen receptor (ER), progesterone receptor (PR), HER2, P53, and P16 to detect the correlation between the improved HER2 scoring method and pathological parameters.

According to the improved HER2 scoring system, among all 1,448 BC cases, HER2-negative, HER2 ultra-low, HER2 low, and HER2-positive BCs accounted for 15.19% (220/1,448), 7.87% (114/1,448), 58.70% (850/1,448), and 18.23% (264/1,448), respectively. A significant difference was observed in the distribution of HER2 scores between hormone receptor-positive (HR+) BCs and HR-negative (HR-) BCs. However, no significant differences were found between the improved and traditional HER2 scoring methods. Moreover, 84.81% (1,228/1,448) of BC patients with HER2 ultra-low, HER2 low or HER2-positive BCs had the potential to benefit from ADC therapy.

Although the improved HER2 scoring system is still in its preliminary conceptual phase, due to its lower costs and practicality, this improved HER2 scoring method is expected to considerably simplify the evaluation of HER2 status and offer more precise guidance for the application of ADCs in BC treatment. Consequently, it is becoming increasingly imperative to conduct multicenter prospective studies to explore the clinical significance of this refined HER2 scoring system.