This retrospective analysis examined changes in HER2 status in residual invasive breast carcinoma following neoadjuvant HER2-targeted therapy (NAT) in patients initially diagnosed with HER2-positive breast cancer. The study focused on how often HER2 overexpression is lost in residual tumor after NAT and the potential clinicopathologic correlates of that change.
Residual tumors were evaluated at a single institution. Post-treatment HER2 status was assessed primarily by immunohistochemistry (IHC) for all available residual invasive tumor specimens. Cases with IHC 2+ underwent confirmatory testing using fluorescence in situ hybridization (FISH) to determine HER2 gene amplification. Tumors were classified into two categories for analysis: HER2-retained and HER2-change, based on combined IHC/FISH results.
From a cohort of 161 patients with HER2-positive breast cancer who received HER2-targeted NAT between 2016 and 2025, 65 patients had sufficient residual invasive tumor for HER2 reassessment. The predominant histologic type among those with assessable residual disease was invasive ductal carcinoma. Details on specific neoadjuvant regimens and duration were not reported in the abstract.
For the purposes of this study:
Among the 65 patients with evaluable residual invasive tumor, 28 cases (43%) retained HER2 overexpression by the study criteria. In contrast, 37 cases (57%) demonstrated a change in HER2 status, consistent with loss of HER2 overexpression or loss of amplification on the residual tumor after HER2-targeted NAT. These rates indicate that, in this series, a majority of residual tumors no longer met criteria for HER2 overexpression following preoperative HER2-directed treatment.
Pre-neoadjuvant therapy hormone receptor (HR) positivity was common in both groups: 23 of 28 (82.1%) in the HER2-retained group and 33 of 37 (89.2%) in the HER2-change group. The authors report that clinicopathologic parameters were comparable between HER2-retained and HER2-change groups based on available data in the abstract. The abstract does not provide additional subgroup outcomes, survival data, or detailed pathologic response metrics.
The authors note that current national and international guidelines recommend continuation of adjuvant HER2-targeted therapy regardless of HER2 status on the post-treatment specimen. Given the observed frequency of HER2 loss in residual disease, the study highlights a clinical uncertainty: whether patients whose residual tumor no longer overexpresses HER2 derive the same benefit from continued adjuvant HER2-directed agents as those with persistent HER2 overexpression. The authors call for prospective randomized phase II/III trials to determine the benefit of adjuvant HER2-targeted therapy specifically in the subgroup whose residual tumors demonstrate loss of HER2 overexpression.
This report is limited by its retrospective design and by originating from a single institution. The abstract does not report detailed treatment regimens, timing of post-treatment tissue sampling, or long-term outcome data for the cohorts defined by post-NAT HER2 status. The authors emphasize the need for prospective randomized trials to clarify whether adjuvant HER2-targeted therapy should be modified based on HER2 status of the residual tumor after NAT.
In summary, this study found that loss of HER2 overexpression in residual breast carcinoma after neoadjuvant HER2-targeted therapy occurred in a majority of evaluable cases (57% in this series). While guidelines currently endorse adjuvant HER2-targeted treatment regardless of post-treatment HER2, the frequent occurrence of HER2 status change supports the need for prospective trials to guide adjuvant management in this subgroup.