ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2025
Prognostic value of residual disease (RD) biology and gene expression changes during the neoadjuvant treatment in patients with HER2-positive early breast cancer (EBC).
Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed.
- Comparative safety of concurrent adjuvant trastuzumab emtansine vs trastuzumab with radiotherapy in HER2-positive early breast cancer.The oncologist · 2026Observational
- Residual disease after neoadjuvant therapy in HER2-positive breast cancer: biology, burden, or both?Translational cancer research · 2026Article
- Immune profiling in residual disease: refining risk stratification after neoadjuvant therapy in HER2-positive breast cancer.Translational cancer research · 2026Article
- Adjuvant ovarian function suppression and aromatase inhibitors in premenopausal patients with hormone receptor and HER2 positive breast cancer, by timing of chemotherapy and trastuzumab and response to neoadjuvant therapy.Breast (Edinburgh, Scotland) · 2026Article
- Antibody-drug conjugates in triple-negative breast cancer (2010-2024): a bibliometric analysis of global trends and clinical translation.Discover oncology · 2025Article
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Abstract
backgroundIn human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), we investigated tumor and immune changes during neoadjuvant treatment and their impact on residual disease (RD) biology and prognostic implications across four neoadjuvant studies of trastuzumab with or without lapatinib, and with or without chemotherapy: CALGB 40601, PAMELA, NeoALTTO, and NSABP B-41. PATIENTS AND
methodsWe compared tumor and immune gene expression changes during neoadjuvant treatment and their association with event-free survival (EFS) by uni- and multivariable Cox regression models in different cohorts and timepoints: 452 RD samples at baseline including 169 with a paired RD, and biomarker changes during neoadjuvant therapy, evaluating model performance via the c-index.
resultsAnalysis of 169 paired tumor samples revealed a shift in intrinsic subtype proportions from HER2-enriched at baseline (50.3%) to normal-like (49.1%) followed by luminal A (18.9%) in RD. This luminal phenotypic change was supported by decreased correlation to the HER2-enriched centroid, ERBB2, and HER2 amplicon genes and increased correlation to the luminal A centroid (Wilcoxon test P < 0.001). Additionally, RD showed relative immune activation marked by significant increases in B-cell, CD8 T-cell, and natural killer cell signatures (Wilcoxon test P < 0.05). In multivariable Cox models, intrinsic subtypes at baseline provided more prognostic information, while immune gene expression signatures provided more prognostic information in RD. Notably, the best multivariable EFS model (c-index = 0.77) integrated the immunoglobulin G signature from RD samples (adjusted hazard ratio 0.45, 95% confidence interval 0.30-0.67, adjusted P = 0.002).
conclusionsIn patients with HER2-positive EBC and RD, tumor biomarkers provide more prognostic information at baseline. In contrast, immune biomarkers perform better for EFS prognosis in RD.
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