319P - The impact of low HER2 expression on clinical significances and outcomes in patients with HER2-negative early breast cancer

Background

HER2-low, defined by immunohistochemically (IHC) 1+ or 2+ with negative in situ hybridization (ISH), has recently attracted attention as a novel classification in determining treatment strategies in HER2-negative metastatic breast cancer (BC). However, clinical significance of this new subcategory in early-stage BC and testing methodologies of HER2-low remain unclear.

Methods

We retrospectively reviewed the clinical data of 1,359 patients with HER2-negative BC at stage I-III between January 2008 and December 2017 in our institute. They were classified into HER2-low (n=455) and HER2-0 (n=904) subgroups according to IHC assay or gene amplification on ISH. We compared the difference in clinicopathological characteristics, recurrence-free survival (RFS), and overall survival (OS) between these subgroups. Since three different immunostaining kits (HercepTest; Dako (i), Bond III stainer (Leica Biosystems) (ii), Ventana ultra View PATHWAY HER2/neu (4B5) (iii)) were used in defining HER2 expression depending on period, we also evaluated the frequency of HER2 expression level by immunostaining kits.

Results

The median age was 57 (range 24–87) and the median follow-up period was 77 months (range 1.1–175.6). The number of patients at clinical stage I, II, and III was 790, 462, and 107, respectively. The HER2-low subgroup tended to have lower histological grade (p < 0.01) and higher frequency of hormone receptor positivity (p < 0.01) compared to the HER2-0 subgroup. There were no statistically significant differences in RFS (p = 0.95) or OS (p = 0.87) between two subgroups. Intriguingly, there were significant differences in the percentages of HER2-low and HER2-0, depending on the immunostaining kits (42.2% vs 57.8% (i), 84.5% vs 15.5% (ii), 87.9% vs 12.1% (iii)).

Conclusions

In this study, there was no prognostic difference based on HER2 expression status in HER2-negative early-stage BC, but there was a frequency difference in determining HER2-low and HER2-0 depending on the immunostaining kits. While there are many assays for HER2 evaluation approved in the practice, an appropriate companion diagnosis for HER2-low seems to be critical to select patients who may benefit from newer treatment such as Trastuzumab Deruxtecan.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.