# Impact of HER2 immunohistochemistry score on pathological complete response and survival in HER2-positive breast cancer treated with neoadjuvant therapy: differential outcomes by hormone receptor status

## TL;DR

Higher HER2 protein expression (IHC 3+) in breast cancer patients is linked to better responses to neoadjuvant therapy and improved survival outcomes.

## Contribution

The study reveals that HER2 IHC score and hormone receptor status influence treatment response and survival in HER2-positive breast cancer.

## Key findings

- HER2 3+ patients had a significantly higher pCR rate compared to HER2 2+/FISH+ patients.
- Dual-target therapy improved pCR in HER2 3+ but not in HER2 2+/FISH+ patients.
- DFS was better in HER2 3+ patients within the HR-positive subgroup.

## Abstract

To investigate the impact of differences in HER2 protein expression level based on immunohistochemistry (IHC) score (HER2 3+ vs. HER2 2+/FISH+) on the pathological complete response (pCR) rate and patient prognosis in HER2-positive breast cancer treated with neoadjuvant therapy(NAT).

This retrospective study analyzed the clinicopathological data of 308 breast cancer patients with pathologically confirmed HER2-positive status (HER2 3+ or HER2 2+/FISH+) who received NAT combined with targeted therapy at our hospital from January 2017 to December 2020. The primary observation indicators were pCR rate and disease-free survival (DFS).

The pCR rate in the HER2 3+ group (252 patients, 81.8%) was significantly higher than that in the HER2 2+/FISH+ group (56 patients, 18.2%) (52.4% vs. 28.6%, P<0.001). Among targeted therapy regimens, patients in the HER2 3+ group receiving dual-target therapy with trastuzumab plus pertuzumab had a higher pCR rate compared to trastuzumab monotherapy (63.0% vs. 46.2%, P = 0.008), while patients in the HER2 2+/FISH+ group did not show significant benefit from dual-target therapy (31.8% vs. 26.5%, P = 0.774). Multivariate analysis identified HER2 IHC 3+, dual-target therapy, and hormone receptor (HR)-negative status as independent favorable factors for achieving pCR. During a median follow-up of 49 months, there was no statistically significant difference in DFS between the two groups (HER2 2+/FISH+ group 77.6% vs. HER2 3+ group 84.5%, P = 0.240). However, in the HR-positive subgroup, DFS was significantly better in the HER2 3+ group compared to the HER2 2+/FISH+ group (P = 0.024).

High HER2 protein expression (IHC 3+) is a predictive factor for achieving a higher pCR rate with NAT in HER2-positive breast cancer. For HER2 2+/FISH+ patients, the benefit from the current standard dual-targeted therapy (trastuzumab + pertuzumab) is limited. For HER2 2+/FISH+ patients, the benefit from the current standard dual-targeted therapy (trastuzumab + pertuzumab) appears limited based on our data. However, due to the small sample size of this subgroup, this finding should be considered preliminary and requires validation in larger cohorts. These findings suggest limitations in current anti-HER2 therapy based on the existing HER2 classification. Future strategies should incorporate HER2 expression level and HR status to develop more precise individualized treatment plans.