In conclusion re evaluation of

In conclusion, re-evaluation of HER2 status is necessary to determine the appropriate use of anti-HER2–targeted therapy beyond disease progression. EGFR and c-met amplification, as well as PIK3CA mutation, are rarely associated with acquired resistance. Our results highlight the importance of formalin fixation conditions for reliable HER2 testing.
Funding This study was financially supported by Chugai Pharmaceutical Co., Ltd.
Conflict of interest statement Some of the authors have financial relationship with Chugai Pharmaceutical Co., Ltd, Japan attached as separate items.
Acknowledgements
Introduction Nowadays, the increase of diseases, especially cancers, is a major global concern. Among different cancers, breast cancer is one of the most common malignancies and diagnosed cancers in women (DeSantis et al., 2015). More than 90% of these deaths are related to metastatic growth. Therefore, early stage detection of cancer is crucial to increase the chances of survival. Human epidermal growth factor 4 hydroxytamoxifen 2 (HER2) protein, a transmembrane tyrosine kinase receptor and a member of the epidermal growth factor receptors (EGFR or ErbB) family, is overexpressed in breast, ovarian, lung, gastric, and oral cancers (Ilkhani et al., 2015, Vivek et al., 2014). Breast cancer patients possess high HER2 concentrations in their blood (14–75 ng mL−1) compared to normal individuals (4–14 ng mL−1) and can be utilized for diagnosis and active surveillance of patients at risk or in treatment (Arya et al., 2018). Currently, various HER2 detection techniques have been reported, including immunohistochemical assays (Arkan et al., 2015, Bethune et al., 2015), enzyme-linked immunosorbent assay (Furrer et al., 2015), surface enhanced Raman scattering (Téllez-Plancarte et al., 2018), fluorescence (Chinen et al., 2015), electrochemiluminescence (Emami et al., 2014, Ravalli et al., 2016), and electrochemical techniques (Ilkhani et al., 2016). However, most of these techniques require sophisticated instrumentation, special training and are labor-intensive and time-consuming. In this context, the electrochemical detection technique has attracted great attention for its simple equipment and high sensitivity (Ju and Chen, 2015). Aptamers, single strand oligonucleotides (DNAs or RNAs) that are designed and developed synthetically in the laboratory, display highly specificity to bind with various targets, such as proteins (Toh et al., 2015), circulating tumor cells (CTCs) (Shan et al., 2018), circulating tumor DNA (ctDNA) (Ilkhani and Farhad, 2018, Li et al., 2018a), and exosomes (Dong et al., 2018). Their prominent properties including good thermal and chemical stability, low cost, high reusability, and easy modification enable them to become a perfect tool in biosensor applications and disease diagnosis (Bala et al., 2016). Thereby, combining electrochemical techniques with the overwhelming aptamers, the electrochemical aptasensors are particularly suitable for constructing rapid, sensitive, miniaturized, and on-site testing platforms. Various electrochemical biosensors for detecting HER2 have been developed based on different nanomaterials, such as the rGO-chit composite (Tabasi et al., 2017), thiol terminated DNA aptamer (Arya et al., 2018), and bimetallic MnFe Prussian blue analogue (Zhou et al., 2019). Additionally, aside from the sensitive determination of cancer markers by electrochemical techniques, the living cancer cells also can be detected using electrochemical aptasensors (Zhang et al., 2018). Since the density of cancer cells in peripheral bloodies is relatively lower, early stage determination still remains a major challenge and it is urgently desired to develop a fast, cost effective, specific and ultrasensitive method for monitoring cancer (Ye et al., 2015). Also, the simultaneous detection of cancer markers and living cells by electrochemical techniques has been seldom reported, because the sensitive layer therein needs to meet the requirements of both electrochemical activity and fluorescence performance. Very recently, a porphyrin-based covalent–organic framework has been exploited as a bifunctional sensing layer for detecting trace EGFR and living michigan cancer foundation-7 (MCF-7) (Yan et al., 2019). Nevertheless, it is still necessary to develop feasible biosensors with the comprehensive properties for detecting biomarkers and cancer cells.