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Background: We aimed to determine the distribution of intrinsic subtypes within HER2-low breast cancer (BC), and to describe the prognostic impact of HER2-low status on survival outcomes.
Methods: This is a retrospective, observational study of primary BC extracted from The Cancer Genome Atlas dataset. We described the distribution of PAM50 intrinsic subtypes within HER2-low BC subtype according to hormonal receptor status (positive (HR+) and negative (HR-)). Secondly, we assessed the impact of HER2-low on survival outcomes (progression-free interval (PFI), disease-free interval (DFI), and overall survival (OS)).
Results: We analyzed 804 primary BCs, including 410 (51%) HER2-low BCs (336 HR+ and 74 HR-). The proportion of HER2-enriched tumors was higher in the HER2-low/HR- group compared to HER2-low/HR+ (13.7% versus 1.2%, respectively). HER2-enriched tumors were more frequent in HER2-low/HR- and HER2-low/HR+ subtypes, compared to HER2-negative/HR- and HER2-negative/HR+ subtypes, respectively (13.7% versus 1.6% and 1.2% versus 0.5%, respectively). We observed no significant differences in PFI, DFI, and OS between HER2-low subtypes and each non-HER2-low subtype paired by HR status.
Conclusions: Our characterization of PAM50 intrinsic subtypes within HER2-low breast cancer may explain the different clinical behaviors and responses to treatment, and ultimately support further investigation of new treatment strategies in the HER2-low category. Moreover, it highlights the importance of considering HR status in the HER2-low category.
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http://dx.doi.org/10.3390/cancers13112824 | DOI Listing |
World J Surg Oncol
September 2025
Department of Breast Surgery, The Affiliated Huizhou Hospital, Guangzhou Medical University, No.1 Xuebei Road, Huizhou, Guangdong, 516000, China.
Introduction: HER2-negative breast cancers can be further subclassified into HER2-low and HER2-zero subtypes. The DESTINY-Breast04 trial has established HER2-low as a research hotspot, with recent studies indicating superior survival rates in HER2-low patients than HER2-zero patients. The impact of heterogeneous hormone receptor (HR) expression patterns on HER2-negative breast cancer has not been comprehensively investigated.
View Article and Find Full Text PDFClin Transl Oncol
September 2025
Servicio de Oncología Médica (Medical Oncology Department), Hospital Universitario Puerta del Mar, Avenida de Ana de Viya 21, 11009, Cádiz, Spain.
Purpose: Human epidermal growth factor receptor 2 (HER2)-negative breast cancer includes HER2-zero and HER2-low tumors. Whether their clinical features and survival are different is not fully clarified. The objective was to explore their clinicopathologic differences and survival.
View Article and Find Full Text PDFQuant Imaging Med Surg
September 2025
Department of Radiology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China.
Background: Accurate preoperative human epidermal growth factor receptor 2 (HER2) status assessment is crucial for guiding treatment selection, particularly with the emergence of anti-HER2 antibody-drug conjugates (ADCs) for HER2-low breast cancer. However, current immunohistochemistry (IHC)-based classification is limited by spatial heterogeneity and sampling bias. Quantitative analysis of intra- and peri-tumoral heterogeneity (ITH) on imaging may offer a non-invasive, objective, and reproducible approach to distinguish HER2-low breast cancer from other subtypes.
View Article and Find Full Text PDFCancer Med
September 2025
Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
Purpose: Human epidermal growth factor receptor 2 (HER2) is a key biomarker for clinical management and prognostic evaluation of breast cancer patients. This study was aimed at assisting the preoperative and non-invasive prediction of HER2-low breast cancer using multimodal ultrasound imaging and clinicopathological indicators, providing valuable imaging information for clinical precision diagnosis and personalized treatment strategies, especially in the application of antibody-drug conjugates such as T-DXd.
Materials And Methods: This retrospective study included 147 pathologically confirmed breast cancer patients from two institutions: 101 in the training set and 46 in the external validation set.
Appl Immunohistochem Mol Morphol
September 2025
Departments of Pathology.
Adopting a HER2-specific treatment approach for HER2-low breast cancer has been suggested after DESTINY-Breast04 (phase 3) trials. Hence, accurate pathologic evaluation gained higher importance, making interobserver agreement and interassay agreement questionable in this regard. To evaluate these, a cohort of 116 invasive breast cancer cases were stained with Dako A0485 and Ventana 4B5.
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