HER2 status change in residual breast carcinoma after neoadjuvant HER2-targeted therapy in patients with HER2-positive breast cancer.

Abstract

Purpose: Assessment of HER2 status change in HER2-positive breast carcinoma (BC) prior to and after HER2-targeted neoadjuvant therapy (NAT) may potentially impact adjuvant HER2-targeted therapy. Reported rates of HER2 status change vary widely (< 10-56%), underscoring the need for further study. This study evaluated the frequency of HER2 status change and its clinicopathologic correlations in HER2-positive BC cases.

Design: Residual breast carcinomas were retrospectively assessed at a single institution after HER2-targeted NAT. HER2 status on residual tumor was evaluated by immunohistochemistry (IHC) and, for IHC 2 + cases, confirmed by fluorescence in situ hybridization (FISH). Tumors were categorized as HER2-retained (IHC 3 + or 2+/FISH amplified) or HER2-change (IHC 0/1 + or 2+/FISH non-amplified). Clinicopathologic features were correlated with post-treatment HER2 status.

Results: Among 161 HER2-positive BC patients treated with HER2-targeted NAT between 2016 and 2025, 65 had adequate residual invasive tumor for HER2 assessment. Invasive ductal carcinoma was the predominant histologic type. Retained HER2 overexpression was observed in 28/65 (43%) cases, while 37/65 (57%) showed HER2 status change. Pre-NAT hormone receptor positivity was present in 23 (82.1%) HER2-retained and 33 (89.2%) HER2- status changed cases. Clinicopathologic parameters were comparable between the groups.

Conclusion: HER2 status change from HER2 overexpression to loss of overexpression occurred in more than half of residual breast carcinomas following HER2-targeted NAT. The current national and international guidelines recommend adjuvant HER2-targeted therapy regardless of post-treatment HER2. Prospective randomized phase II/III trials are needed to determine the benefit of adjuvant HER2-targeted therapy in this subgroup of patients with HER2-positive BC.