ArticleAnnals of surgical oncology2025
Immunohistochemical Status Predicts Pathologic Complete Response to Neoadjuvant Therapy in HER2-Overexpressing Breast Cancers.
Article in Annals of surgical oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Neoadjuvant Dual-Targeted HER2 Therapy and Neoadjuvant Chemo-Immunotherapy is Associated with Improved Nodal pCR and Reduced Axillary Surgery.Annals of surgical oncology · 2026Article
- Predictors of Pathological Complete Response to Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer: Development and Validation of a Clinical-Inflammatory Nomogram.Annals of surgical oncology · 2026Article
- Clinical complete response and predictive factors in HER2-positive early breast cancer treated with neoadjuvant chemotherapy aimed at omission of surgery: an exploratory analysis of the JCOG1806 trial.International journal of clinical oncology · 2026Article
- HER2 expression in breast cancer: evidence gaps and challenges.NPJ precision oncology · 2025Review
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9 authors.
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Abstract
backgroundHuman epidermal growth factor receptor 2 (HER2) overexpression (HER2+) is defined by immunohistochemistry (IHC) and in situ hybridization (ISH) as IHC3+ or IHC2+/ISH+. Response differences to neoadjuvant anti-HER2 therapy (NT) in IHC3+ versus IHC2+/ISH+ breast cancer patients are poorly characterized. We explored whether pathologic complete response (pCR) varies by HER2 IHC status.
methodsPatients with stage I-III HER2+ breast cancer undergoing NT and surgery between 2013 and 2020 were identified from the National Cancer Database and stratified by IHC status. Breast and nodal pCR were analyzed.
resultsOf 40,711 HER2+ patients, 83% were IHC3+ and 17% were IHC2+/ISH+. IHC3+ patients were more likely to be hormone receptor (HR)-negative (33 vs. 21%), have cT3/4 tumors (24 vs. 21%), and be cN+ (52 vs. 47%; all p < 0.0001). Breast conservation rates were similar (each 43%, p = 0.32), although IHC3+ axillary lymph node dissection rates were lower (41 vs. 45%, p < 0.0001). Among all patients, breast pCR was 49%, while nodal pCR was 64%. Compared with IHC2+/ISH+, IHC3+ had higher unadjusted breast (54 vs. 22%, p < 0.0001) and nodal (69 vs. 37%, p < 0.0001) pCR rates. When stratified by HR status, pCR was lower for HR+ disease but remained higher among IHC3+ patients. Analysis of T1cN0 primaries mirrored these trends. In multivariable analysis, IHC3+ remained an independent predictor of breast (odds ratio [OR] 3.91, confidence interval [CI] 3.65-4.19, p < 0.0001) and nodal (OR 3.40, CI 3.12-3.71, p < 0.0001) pCR.
conclusionHER2 IHC status predicts pCR and may help select breast cancer patients who derive the greatest benefit from NT. These findings provide further evidence that revision of HER2 classification may improve clinical management.
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