Characterization of CTC-HER2 Status in Patients with HER2-Low Invasive Breast Cancer
- 1Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Unit 1484, Houston, TX 77030, USA
- 2Department of Biostatistics, University of Texas MD Anderson Cancer Center, 7007 Bertner Avenue, Unit 1689, Houston, TX 77030, USA
Abstract
Background: HER2 status is a dynamic process where one in ten patients with invasive breast cancer may undergo receptor conversion. We characterized HER2 status on circulating tumor cells (CTCs) in patients with HER2-low breast cancer. Methods: Patients with HER2-low expression, defined as immunohistochemistry (IHC) score of 1+ or 2+ with negative HER2 fluorescent in situ hybridization, were enrolled from 2019 to 2023. All patients were treatment-naïve to HER2-targeted therapies. Blood draws were collected serially q3–6 months. CTCs were enumerated using CellSearch™ and HER2 expression on CTCs were detected using an anti-HER2 fluorescent antibody. Presence of ≥1 CTCs was considered positive. Wilcoxon rank-sum, Fisher’s exact test, and Kaplan–Meier method were used for statistical analysis. Results: Among 39 HER2-low patients, median age was 49.0 years (IQR 40.5–58.5). Patients were predominantly Non-Hispanic White (26, 66.7%), with node-positive (29/38, 76.3%), ductal (27, 69.2%), stage II-III (24, 61.5%) disease. Over half (23, 59.0%) had inflammatory breast cancer (IBC). Rates of ER and PR positivity were 56.4% (22) and 51.3% (20), respectively. Majority of patients underwent surgery (23 mastectomy, seven segmental mastectomy) with a pCR rate of 17.2%. Up to 53.8% (21) of patients had HER2-positive CTCs during treatment course. Of these, 13 (61.9%) and eight (38.1%) were present before and after surgery, respectively. There were no differences in age, BMI, grade, histology, lymphovascular invasion, IBC status, and pCR rate by CTC-HER2 status. At a median follow up of 3.8 years (95% CI: 2.6–4.9), patients with HER2-positive CTCs demonstrated a trend of worse prognosis compared to those with HER2-negative CTCs (5-year overall survival 59.8% vs. 88.9%, p = 0.11). Conclusions: In this study cohort, a high proportion of HER2-low expressors demonstrated HER2-CTC positivity. These findings support the potential use of HER2 expression on CTCs as a biomarker to personalize therapies among patients with HER2-low breast cancer.
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BibTeX
@article{chen2026characterization,
title = {{Characterization of CTC-HER2 Status in Patients with HER2-Low Invasive Breast Cancer}},
author = {Jennifer H. Chen and Salyna Meas and Roland L. Bassett and Vanessa N. Sarli and Joshua Upshaw and Anthony Lucci},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18203265},
url = {https://www.mdpi.com/2072-6694/18/20/3265},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Characterization of CTC-HER2 Status in Patients with HER2-Low Invasive Breast Cancer
AU - Jennifer H. Chen
AU - Salyna Meas
AU - Roland L. Bassett
AU - Vanessa N. Sarli
AU - Joshua Upshaw
AU - Anthony Lucci
PY - 2026
DA - 2026/10/01
JO - Cancers
DO - 10.3390/cancers18203265
UR - https://www.mdpi.com/2072-6694/18/20/3265
AB - Background: HER2 status is a dynamic process where one in ten patients with invasive breast cancer may undergo receptor conversion. We characterized HER2 status on circulating tumor cells (CTCs) in patients with HER2-low breast cancer. Methods: Patients with HER2-low expression, defined as immunohistochemistry (IHC) score of 1+ or 2+ with negative HER2 fluorescent in situ hybridization, were enrolled from 2019 to 2023. All patients were treatment-naïve to HER2-targeted therapies. Blood draws were collected serially q3–6 months. CTCs were enumerated using CellSearch™ and HER2 expression on CTCs were detected using an anti-HER2 fluorescent antibody. Presence of ≥1 CTCs was considered positive. Wilcoxon rank-sum, Fisher’s exact test, and Kaplan–Meier method were used for statistical analysis. Results: Among 39 HER2-low patients, median age was 49.0 years (IQR 40.5–58.5). Patients were predominantly Non-Hispanic White (26, 66.7%), with node-positive (29/38, 76.3%), ductal (27, 69.2%), stage II-III (24, 61.5%) disease. Over half (23, 59.0%) had inflammatory breast cancer (IBC). Rates of ER and PR positivity were 56.4% (22) and 51.3% (20), respectively. Majority of patients underwent surgery (23 mastectomy, seven segmental mastectomy) with a pCR rate of 17.2%. Up to 53.8% (21) of patients had HER2-positive CTCs during treatment course. Of these, 13 (61.9%) and eight (38.1%) were present before and after surgery, respectively. There were no differences in age, BMI, grade, histology, lymphovascular invasion, IBC status, and pCR rate by CTC-HER2 status. At a median follow up of 3.8 years (95% CI: 2.6–4.9), patients with HER2-positive CTCs demonstrated a trend of worse prognosis compared to those with HER2-negative CTCs (5-year overall survival 59.8% vs. 88.9%, p = 0.11). Conclusions: In this study cohort, a high proportion of HER2-low expressors demonstrated HER2-CTC positivity. These findings support the potential use of HER2 expression on CTCs as a biomarker to personalize therapies among patients with HER2-low breast cancer.
SN - 2072-6694
ER -