RESUMEN
Human epidermal growth factor receptor 2 (HER2)-enriched breast cancer benefits significantly from anti-HER2 targeted therapies. This highlights the critical need for precise HER2 immunohistochemistry (IHC) interpretation serving as a triage tool for selecting patients for anti-HER2 regimens. Recently, the emerging eligibility of patients with HER2-low breast cancers for a novel HER2-targeted antibody-drug conjugate (T-DXd) adds challenges to HER2 IHC scoring interpretation, notably in the 0-1+ range, which shows high interobserver and interlaboratory staining platform variability. In this review, we navigate evolving challenges and suggest practical recommendations for HER2 IHC interpretation.
Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama , Inmunohistoquímica , Receptor ErbB-2 , Humanos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico , Receptor ErbB-2/metabolismo , Receptor ErbB-2/análisis , Femenino , Inmunohistoquímica/métodos , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismoRESUMEN
AIM: To determine the frequency of MED12 mutations in a series of 112 breast phyllodes tumours, and to correlate the findings with clinicopathological parameters and survival outcomes. METHODS: Phyllodes tumours from the Department of Pathology, Singapore General Hospital, were classified into benign, borderline and malignant categories. Genomic DNA from formalin-fixed paraffin-embedded phyllodes tumours was extracted, purified and subjected to ultra-deep-targeted amplicon sequencing across exon 2 of the MED12 gene. Sequencing was performed on the Illumina MiSeq next-generation sequencing platform and bioinformatics analysis applied. Appropriate statistical analyses were carried out. RESULTS: There were 66 benign, 32 borderline and 14 malignant tumours, with 43 (65.1%), 21 (65.6%) and 6 (42.8%) disclosing MED12 mutations (missense, splice site, indel), respectively. For 97 cases with available follow-up, there were 10 (10.3%) recurrences. Patients with phyllodes tumours that harboured MED12 mutations experienced improved disease-free survivals, with higher recurrence likelihood in those without MED12 mutations (HR 9.99, 95% CIs 1.55 to 64.42, p=0.015). CONCLUSIONS: Similar to fibroadenomas, phyllodes tumours show a high frequency of MED12 mutations, affirming the close biological relationship between these fibroepithelial neoplasms.