HER2 quantitative continuous scoring for accurate patient selection in HER2 negative trastuzumab deruxtecan treated breast cancer.

Autor: Kapil A; Computational Pathology, Oncology R&D, AstraZeneca, Bernhard-Wicki-Straße 5, 80636, München, Bayern, Germany. ansh.kapil@astrazeneca.com., Spitzmüller A; Computational Pathology, Oncology R&D, AstraZeneca, Bernhard-Wicki-Straße 5, 80636, München, Bayern, Germany., Brieu N; Computational Pathology, Oncology R&D, AstraZeneca, Bernhard-Wicki-Straße 5, 80636, München, Bayern, Germany., Haneder S; Computational Pathology, Oncology R&D, AstraZeneca, Bernhard-Wicki-Straße 5, 80636, München, Bayern, Germany., Shumilov A; Computational Pathology, Oncology R&D, AstraZeneca, Bernhard-Wicki-Straße 5, 80636, München, Bayern, Germany., Meier A; Computational Pathology, Oncology R&D, AstraZeneca, Bernhard-Wicki-Straße 5, 80636, München, Bayern, Germany., Cecchi F; Translational Medicine, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA., Barkell A; Translational Medicine, Oncology R&D, AstraZeneca, Cambridge, UK., Harder N; Computational Pathology, Oncology R&D, AstraZeneca, Bernhard-Wicki-Straße 5, 80636, München, Bayern, Germany., Mittermaier K; Computational Pathology, Oncology R&D, AstraZeneca, Bernhard-Wicki-Straße 5, 80636, München, Bayern, Germany., Hidalgo-Sastre A; Computational Pathology, Oncology R&D, AstraZeneca, Bernhard-Wicki-Straße 5, 80636, München, Bayern, Germany., Alleze R; Computational Pathology, Oncology R&D, AstraZeneca, Bernhard-Wicki-Straße 5, 80636, München, Bayern, Germany., Schick M; Computational Pathology, Oncology R&D, AstraZeneca, Bernhard-Wicki-Straße 5, 80636, München, Bayern, Germany., Schmidt G; Computational Pathology, Oncology R&D, AstraZeneca, Bernhard-Wicki-Straße 5, 80636, München, Bayern, Germany., Sade H; Computational Pathology, Oncology R&D, AstraZeneca, Bernhard-Wicki-Straße 5, 80636, München, Bayern, Germany., Tsuchihashi Z; Translational Science, Daiichi Sankyo, Inc., Basking Ridge, NJ, USA., Suto F; Translational Science, Daiichi Sankyo, Inc., Basking Ridge, NJ, USA., Gustavson M; Translational Medicine, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA., Barrett JC; Translational Medicine, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA., Carroll D; Translational Medicine, Oncology R&D, AstraZeneca, Cambridge, UK.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 May 27; Vol. 14 (1), pp. 12129. Date of Electronic Publication: 2024 May 27.
DOI: 10.1038/s41598-024-61957-9
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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