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Multiomic factor analysis for pathologic complete response after pembrolizumab + trastuzumab + pertuzumab in HER2-enriched early breast cancer: WSG-keyriched-1 trial : translational mechanisms and therapy

We performed multiomic factor analysis of biomarkers potentially associated with pathologic complete response (pCR) after a chemotherapy-free combination of immunotherapy and dual ERBB2 (HER2) blockade.Forty-eight patients with HER2 2+ (ISH+) or 3+ early breast cancer, stage I to III, and HER2-enric...

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Main Authors: Graeser, Monika (Author) , Gluz, Oleg (Author) , Schmid, Peter (Author) , Jóźwiak, Katarzyna (Author) , zu Eulenburg, Christine (Author) , Feuerhake, Friedrich (Author) , Volk, Valery (Author) , Ulbrich-Gebauer, Daniel (Author) , Biehl, Claudia (Author) , Reinisch, Mattea (Author) , Lüdtke-Heckenkamp, Kerstin (Author) , Hartkopf, Andreas (Author) , Hilpert, Felix (Author) , Braun, Michael (Author) , Blohmer, Jens Uwe (Author) , Christgen, Matthias (Author) , Kreipe, Hans Heinrich (Author) , Nitz, Ulrike (Author) , Pelz, Enrico (Author) , Harbeck, Nadia (Author) , Kuemmel, Sherko (Author)
Format: Article (Journal)
Language:English
Published: 1 January 2026
In: Clinical cancer research
Year: 2026, Volume: 32, Issue: 1, Pages: 214-223
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-25-1923
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1078-0432.CCR-25-1923
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Author Notes:Monika Graeser, Oleg Gluz, Peter Schmid, Katarzyna Jóźwiak, Christine zu Eulenburg, Friedrich Feuerhake, Valery Volk, Daniel Ulbrich-Gebauer, Claudia Biehl, Mattea Reinisch, Kerstin Lüdtke-Heckenkamp, Andreas Hartkopf, Felix Hilpert, Michael Braun, Jens Uwe Blohmer, Matthias Christgen, Hans Heinrich Kreipe, Ulrike Nitz, Enrico Pelz, Nadia Harbeck, Sherko Kuemmel, on behalf of the West German Study Group investigators
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Summary:We performed multiomic factor analysis of biomarkers potentially associated with pathologic complete response (pCR) after a chemotherapy-free combination of immunotherapy and dual ERBB2 (HER2) blockade.Forty-eight patients with HER2 2+ (ISH+) or 3+ early breast cancer, stage I to III, and HER2-enriched subtype received pembrolizumab, trastuzumab biosimilar, and pertuzumab. The primary outcome was pCR (ypT0/is ypN0). Multiomic factors representing combined markers from pooling different translational research marker data were identified based on the eigenvalue >1 criteria. Additionally, logistic regressions with elastic net regularization were performed using all single markers, multiomic factors, and clinical characteristics to evaluate their association with pCR.The multiomic factor involving genes related to immune response and tumorigenesis, multiplexed IHC markers related to immune response and HER2 in the stroma, and stromal tumor-infiltrating lymphocytes were associated with pCR. pCR rates were 66.7% and 28.6% in the high (>median) and low (≤median) factor score groups, respectively (unadjusted OR, 5.00; 95% confidence interval, 1.35-18.56; nominal P = 0.016). In the analysis using standardized values for all individual markers from gene expression analysis, multiplexed IHC analysis in the stroma, and stromal tumor-infiltrating lymphocytes, markers with the greatest impact on pCR were the genes FNBP1, CD36, MYCN, and SIX1 (OR between 1.43 and 1.62), and progesterone receptor status (OR, 0.65), which surpassed grade (OR, 1.22) and nodal status (OR, 0.90).Our multiomic analysis uncovered mechanisms of tumor response to immunotherapy combined with dual HER2 blockade. These results could inform the design of larger trials investigating chemotherapy-free regimens in selected patients with HER2+ early breast cancer.
Item Description:Gesehen am 09.03.2026
Im Titel steht bei "pembrolizumab + trastuzumab + pertuzumab" das Pluszeichen
Physical Description:Online Resource
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-25-1923

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