Background Circulating tumor cells (CTCs) can provide the basis for a liquid biopsy and may guide the use of targeted therapies. We report on unbiased quantification of Her-2 protein expression of CTCs. Patients and methods Her-2 assessment of CTCs was carried out using the CellSearch(®) system in 103 metastatic (M1) and 88 non-metastatic (M0) breast-cancer patients. Expression of Her-2 on CTCs was determined by a manual review and an automated algorithm using Her-2- fluorescein isothiocyanate (FITC) fluorescence of leukocytes to determine the Her-2-expression threshold in each sample. Results Her-2 expression of CTCs varied greatly within and among patients compared with Her-2 expression of leukocytes. In M1 patients, a threshold of 75% of Her-2 positive CTCs in patients with ≥5 CTCs was set. Applying this threshold, 9% of M1 patients with Her-2-negative primary tumors had Her-2-positive CTC status and 29% of M1 patients with Her-2-positive primary tumors had Her-2-negative CTC status. No Her-2 discrepancy was observed between CTCs and primary tumors in M0 patients. Conclusions Our findings demonstrate that Her-2 expression is heterogeneous among CTCs within each patient. We show the feasibility of unbiased quantitative and reproducible assessment of treatment targets on CTCs, opening a path towards personalized treatment.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/annonc/mds625 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
HER2 expression and pathway status in male breast cancer patients: results of an integrated analysis among 6,150 patients.
Sci Rep
January 2025
Department of Gastroenterology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710014, Shaanxi Province, China.
The role of human epidermal growth factor 2 (HER2) in male breast cancer (MBC) is poorly defined. A comprehensive description of HER2 status was conducted. A total of 6,015 MBC patients from 45 studies and 135 MBC patients with sequencing data were identified.
View Article and Find Full Text PDFPre-Clinical Rationale for Amcenestrant Combinations in HER2+/ER+ Breast Cancer.
Int J Mol Sci
January 2025
Cancer Biotherapeutics Research Group, Life Sciences Institute, School of Biotechnology, Dublin City University, Dublin 9, D09 NR58 Dublin, Ireland.
HER2-positive/oestrogen receptor-positive (HER2+/ER+) represents a unique breast cancer subtype. The use of individual HER2- or ER-targeting agents can lead to the acquisition of therapeutic resistance due to compensatory receptor crosstalk. New drug combinations targeting HER2 and ER could improve outcomes for patients with HER2+/ER+ breast cancer.
View Article and Find Full Text PDFNatural killer cells occupy unique spatial neighborhoods in HER2 and HER2 human breast cancers.
Breast Cancer Res
January 2025
Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR, 97239, USA.
Tumor-infiltrating lymphocytes are considered clinically beneficial in breast cancer, but the significance of natural killer (NK) cells is less well characterized. As increasing evidence has demonstrated that the spatial organization of immune cells in tumor microenvironments is a significant parameter for impacting disease progression as well as therapeutic responses, an improved understanding of tumor-infiltrating NK cells and their location within tumor contextures is needed to improve the design of effective NK cell-based therapies. In this study, we developed a multiplex immunohistochemistry (mIHC) antibody panel designed to quantitatively interrogate leukocyte lineages, focusing on NK cells and their phenotypes, in two independent breast cancer patient cohorts (n = 26 and n = 30).
View Article and Find Full Text PDFGenomic Characterization and Prognostic Significance of Human Epidermal Growth Factor Receptor 2-Low, Hormone Receptor-Positive, Early Breast Cancers From the BIG 1-98 and SOFT Clinical Trials.
JCO Precis Oncol
January 2025
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Purpose: To investigate whether hormone receptor-positive, human epidermal growth factor receptor 2-low (HR+HER2-low) versus HR+HER2-zero early breast cancers have distinct genomic and clinical characteristics.
Methods: This study included HR+, HER2-negative early breast cancers from patients enrolled in the phase III, randomized BIG 1-98 and SOFT clinical trials that had undergone tumor genomic sequencing. Tumors were classified HR+HER2-low if they had a centrally reviewed HER2 immunohistochemistry (IHC) score of 1+ or 2+ with negative in situ hybridization and HR+HER2-zero if they had an HER2 IHC score of 0.
Antibody-drug conjugates in urothelial carcinoma: current status and future.
Curr Opin Urol
January 2025
Department of Medicine, Division of Hematology and Oncology, New York Presbyterian Weill Cornell Medical Center.
Purpose Of Review: Antibody-drug conjugates (ADCs) are quickly becoming frontline standard of care in many tumor types, including urothelial carcinoma. This review summarizes recent clinical investigations into the use of ADCs targeting nectin-4, trophoblast cell surface antigen-2 (Trop-2), human epidermal growth factor receptor 2 (HER-2), and other antigens in urothelial carcinoma.
Recent Findings: This review covers efficacy and toxicity data of ADCs alone and in combination with immunotherapy; mechanisms of resistance; and preclinical studies that provide biological basis for clinical approaches.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!