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Sci Rep ; 14(1): 12129, 2024 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802399

RESUMO

Many targeted cancer therapies rely on biomarkers assessed by scoring of immunohistochemically (IHC)-stained tissue, which is subjective, semiquantitative, and does not account for expression heterogeneity. We describe an image analysis-based method for quantitative continuous scoring (QCS) of digital whole-slide images acquired from baseline human epidermal growth factor receptor 2 (HER2) IHC-stained breast cancer tissue. Candidate signatures for patient stratification using QCS of HER2 expression on subcellular compartments were identified, addressing the spatial distribution of tumor cells and tumor-infiltrating lymphocytes. Using data from trastuzumab deruxtecan-treated patients with HER2-positive and HER2-negative breast cancer from a phase 1 study (NCT02564900; DS8201-A-J101; N = 151), QCS-based patient stratification showed longer progression-free survival (14.8 vs 8.6 months) with higher prevalence of patient selection (76.4 vs 56.9%) and a better cross-validated log-rank p value (0.026 vs 0.26) than manual scoring based on the American Society of Clinical Oncology / College of American Pathologists guidelines. QCS-based features enriched the HER2-negative subgroup by correctly predicting 20 of 26 responders.


Assuntos
Neoplasias da Mama , Seleção de Pacientes , Receptor ErbB-2 , Trastuzumab , Humanos , Feminino , Receptor ErbB-2/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Trastuzumab/uso terapêutico , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Adulto , Imunoconjugados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Idoso , Imuno-Histoquímica , Camptotecina/análogos & derivados
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