Abstract
Breast cancer is the second most common cause of cancer-related deaths among women worldwide. It is a heterogeneous disease with four major molecular subtypes. One of the subtypes, human epidermal growth factor receptor 2 (HER2)-enriched (HER2-positive) is characterized by the absence of estrogen and progesterone receptors and overexpression of HER2 receptor, and accounts for 15–20% of all breast cancers. Despite the anti-HER2 and cytotoxic chemotherapy, HER2 subtype is an aggressive disease with significant mortality. Recent advances in molecular biology techniques, including gene expression profiling, proteomics, and microRNA analysis, have been extensively used to explore the underlying mechanisms behind human breast carcinogenesis and metastasis including HER2-positive breast cancer, paving the way for developing new targeted therapies. This review focuses on recent advances on gene expression and miRNA status in HER2-positive breast cancer.
Highlights
Breast cancer is the most common type of cancer diagnosed in women worldwide with around2.1 million new cases in 2018 according the World Health Organization
Progress in microarray technology led to gene expression profiling of breast cancer with the aim of identifying patients that can benefit from adjuvant chemotherapy, and as a prognosis predictor in cancer patients [59,60]
MiRNAs have been involved in the onset and progression of breast cancer and have the ability to reverse resistance to drugs like tamoxifen; as studies have shown that re-expression of miR-375 [169], miR-342 [170], and miR-449a [171] suppressed tamoxifen resistance; indicating them to be potential biomarkers for therapeutic strategies. miR-210 levels in plasma are linked with trastuzumab resistance in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients [172]
Summary
Breast cancer is the most common type of cancer diagnosed in women worldwide with around. Cancers 2019, 11, 646 distant metastases, in addition to hormone receptor, estrogen (ER), progesterone (PR) and human epidermal growth factor receptor 2 (HER2) status [9] This has successfully led to decreasing mortality rates over the last three decades, it failed to predict the outcome in different patients, as patients with the same tumor features may have completely different outcomes [9] while other patients suffer from significant toxic side effects [10]. Status or by florescence or chromogenic in situ hybridization (FISH/CISH) of HER2 gene copy number or a HER2/CEP17 ratio of 2 or greater [20] This type of cancer is associated with poor prognosis, short survival, and high rates of recurrence [20]. Amplification or overexpression of HER2 oncoprotein plays an important role in the pathogenesis of various solid tumors [30], including upper gastrointestinal tract (stomach and gastroesophageal junction adenocarcinoma) [31], ovarian cancer, colon, salivary gland [32], lung cancer, and breast cancer [33]
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