Background: Low human epidermal growth factor receptor 2 (HER2) expression is an emerging concept in breast cancer that is defined as immunohistochemistry (IHC) 1 + or IHC 2 + and negative in situ hybridization (ISH) but has been poorly investigated. The aim of our study was to determine the frequency of low HER2 expression among HER2-negative breast cancers and compare the clinicopathological features and prognosis of HER2-low patients with those of HER2-zero patients.
Methods: We collected the data of 684 patients with primary HER2-negative breast cancer who underwent surgery between January 2012 and September 2021 from our self-built database. Clinicopathological features, recurrence-free interval (RFI) and breast cancer-specific survival (BCSS) were compared between HER2-low and HER2-zero (IHC 0) patients.
Results: Among the 684 patients, 512 (74.9%) patients had low HER2 expression, and 172 (25.1%) patients had zero HER2 expression. The average age was 57.7 ± 12.6 years, 472 (69.0%) patients were aged < 65 years, and 212 (31.0%) patients were aged ≥ 65 years. Compared to HER2-zero tumors, HER2-low tumors had a higher proportion of hormone receptor (HR)-positive cases (89.6% vs. 75.6%, P < 0.001) and a lower rate of histological grade III cases (29.4% vs. 38.8%, P < 0.001). Kaplan-Meier analysis showed that low HER2 expression was associated with prolonged RFI in breast cancer patients, especially in HR + breast cancer patients (P = 0.028) and < 65-year-old breast cancer patients (P = 0.000). Multivariate Cox regression analysis showed that low HER2 expression was a low-risk factor for RFI (HR: 0.531, 95% CI: 0.292-0.967, P = 0.038) but had no influence on BCSS (P = 0.272).
Conclusions: HER2-low tumors had a higher proportion of HR positivity and a lower rate of histological grade III than HER2-zero tumors. Low HER2 expression seemed to be a protective factor for RFI, especially in patients with HR + and those younger than 65 years.
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http://dx.doi.org/10.1186/s12885-023-11421-0 | DOI Listing |
Nature
January 2025
Stanford Cancer Institute, School of Medicine, Stanford University, Stanford, CA, USA.
Breast cancer is a highly heterogeneous disease whose prognosis and treatment as defined by the expression of three receptors-oestrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor 2 (HER2; encoded by ERBB2)-is insufficient to capture the full spectrum of clinical outcomes and therapeutic vulnerabilities. Previously, we demonstrated that transcriptional and genomic profiles define eleven integrative subtypes with distinct clinical outcomes, including four ER subtypes with increased risk of relapse decades after diagnosis. Here, to determine whether these subtypes reflect distinct evolutionary histories, interactions with the immune system and pathway dependencies, we established a meta-cohort of 1,828 breast tumours spanning pre-invasive, primary invasive and metastatic disease with whole-genome and transcriptome sequencing.
View Article and Find Full Text PDFEur J Cancer
January 2025
Medical Oncology Department, Hospital 12 de Octubre, Madrid, Spain; Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), Madrid, Spain; SOLTI Cancer Research Group, Barcelona, Spain. Electronic address:
Introduction: The prognostic value of PAM50 intrinsic subtypes (IS), cell cycle, and immune-related gene expression in HR+ /HER2- advanced breast cancer (BC) treated with CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) in a first-line metastatic setting is unclear. This study evaluates these biomarkers in metastatic biopsies from patients diagnosed with HR+ /HER2- advanced BC.
Methods: CDK-PREDICT study is a multicentric, ambispective observational cohort study conducted in six Spanish hospitals.
Korean J Clin Oncol
December 2024
Department of Pathology, Safdarjung Hospital, Vardhman Mahavir Medical College, New Delhi, India.
Purpose: Breast cancer subtypes are delineated by human epidermal growth factor receptor 2 (HER2) expression, pivotal in treatment selection. HER2-positive tumors typically respond to targeted therapies, whereas HER2-negative tumors lack HER2 overexpression. However, a subset exhibits low HER2 expression without amplification, termed HER2 low breast cancer.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning, China.
Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with the worst prognosis among all subtypes. The impact of distinct cell subpopulations within the tumor microenvironment (TME) on TNBC patient prognosis has yet to be clarified.
Methods: Utilizing single-cell RNA sequencing (scRNA-seq) integrated with bulk RNA sequencing (bulk RNA-seq), we applied Cox regression models to compute hazard ratios, and cross-validated prognostic scoring using a GLMNET-based Cox model.
Diagn Pathol
January 2025
Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Studničkova 2, Prague, 12800, Czech Republic.
Background: Juvenile granulosa cell tumor (JGCT) of the ovary is a rare tumor with distinct clinicopathological and hormonal features primarily affecting young women and children. We conducted a complex clinicopathological, immunohistochemical, and molecular analysis of five cases of JGCT.
Methods: The immunohistochemical examination was performed with 32 markers, including markers that have not been previously investigated.
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