ArticleCancer research and treatment2019
Discordance of the PAM50 Intrinsic Subtypes Compared with Immunohistochemistry-Based Surrogate in Breast Cancer Patients: Potential Implication of Genomic Alterations of Discordance.
Article in Cancer research and treatment, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49 citing papers in PubMed, 101 citations in OpenAlex.
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- LUCAT1-Mediated Competing Endogenous RNA (ceRNA) Network in Triple-Negative Breast Cancer.Cells · 2024Article
- Article
- PAM50 breast cancer subtypes and survival of patients in rural Ethiopia without adjuvant treatment: a prospective observational study.BMC cancer · 2024Observational
- Impact of Molecular Profiling on Therapy Management in Breast Cancer.Journal of clinical medicine · 2024Review
- Defining the Regulatory Logic of Breast Cancer Using Single-Cell Epigenetic and Transcriptome Profiling.bioRxiv : the preprint server for biology · 2024Article
- Migratory Tumor Cells Cooperate with Cancer Associated Fibroblasts in Hormone Receptor-Positive and HER2-Negative Breast Cancer.International journal of molecular sciences · 2024Article
- Molecular subtyping improves breast cancer diagnosis in the Copenhagen Breast Cancer Genomics Study.JCI insight · 2024Article
- Differences in Histological Subtypes of Invasive Lobular Breast Carcinoma According to Immunohistochemical Molecular Classification.Diagnostics (Basel, Switzerland) · 2024Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
purposeWe aimed to analyze the discordance between immunohistochemistry (IHC)-based surrogate subtyping and PAM50 intrinsic subtypes and to assess overall survival (OS) according to discordance. MATERIALS AND
methodsA total of 607 patients were analyzed. Hormone receptor (HR) expression was evaluated by IHC, and human epidermal growth factor receptor 2 (HER2) expression was analyzed by IHC and/or fluorescence in situ hybridization. PAM50 intrinsic subtypes were determined according to 50 cancer genes using the NanoString nCounter Analysis System. We matched concordant tumor as luminal A and HR+/HER2-, luminal B and HR+/HER2+, HR-/HER2+ and HER2-enriched, and triple-negative breast cancer (TNBC) and normal- or basal-like. We used Ion Ampliseq Cancer Panel v2 was used to identify the genomic alteration related with discordance. The Kaplan-Meier method was used to estimate OS.
resultsIn total, 233 patients (38.4%) were discordant between IHC-based subtype and PAM50 intrinsic subtype. Using targeted sequencing, we detected somatic mutation-related discordant breast cancer including the VHL gene in the HR+/HER2- group (31% in concordant group, 0% in discordant group, p=0.03) and the IDH and RET genes (7% vs. 12%, p=0.02 and 0% vs. 25%, p=0.02, respectively) in the TNBC group. Among the luminal A/B patients with a discordant result had significantly worse OS (median OS, 73.6 months vs. not reached; p < 0.001), and among the patients with HR positivity, the basal-like group as determined by PAM50 showed significantly inferior OS compared to other intrinsic subtypes (5-year OS rate, 92.2% vs. 75.6%; p=0.01).
conclusionA substantial portion of patients showed discrepancy between IHC subtype and PAM50 intrinsic subtype in our study. The survival analysis demonstrated that current IHC-based classification could mislead the treatment and result in poor outcome. Current guidelines for IHC might be updated accordingly.
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