The role of HER2 alterations in clinicopathological and molecular characteristics of breast cancer and HER2-targeted therapies: a comprehensive review.

Breast cancer (BC) is the most common malignancy in women and one of the leading causes of cancer mortality, despite significant treatment advancements over the last decades. Human epidermal growth factor receptor-2 (HER2) is a member of the ERBB family of receptor tyrosine kinases which have long been known to mediate cancer cell growth and invasion through constitutive activation of oncogenic downstream signaling, such as PI3K/Akt/mTOR and MAPK. Overexpression/amplification of HER2 in various tumors, especially BC, offers the possible therapeutic potential for target therapies. HER2-targeted therapies, either with a combination of chemotherapy or through multi-anti-HER2 therapies without chemotherapy, have significantly improved the prognosis of HER2-positive tumors. In recent years, novel anti-HER2 agents and combination therapies have garnered much attention, especially for heavily treated advanced or metastatic BCs. HER2-positive BC is biologically a heterogeneous group depending on HER2 activation mechanisms, hormone receptor status, genome variations, tumor heterogeneity, and treatment resistance, which affect the treatment benefit and patients' outcomes. This review will discuss HER2 alternations (gene amplification or receptor overexpression) in BC, their correlation with clinicopathological characteristics and molecular characteristics, and HER2-based therapies in tumors with HER2 overexpression/amplification.

A Rare Case of Brain Metastasis from Dedifferentiated Acinic Cell Carcinoma of the Parotid Gland and Review of the Literature.

Acinic cell carcinoma (ACC) is a low or intermediate-grade malignant epithelial neoplasm of the salivary glands that generally shows an indolent behavior. Most cases arise in the major salivary glands, especially the parotid gland. ACC is usually known as a low-grade malignant tumor; however, poorly differentiated and high-grade transformed variants have been reported and may tend to be late recurrence and metastasis. Our case was a 49-year-old woman with a history of a right parotid rapidly growing mass lesion, which was cytologically diagnosed as monomorphic adenoma on fine-needle aspiration (FNA). Finally, the diagnosis of ACC with dedifferentiated components was reported, followed by parotidectomy. After 30 sessions of radiotherapy, she presented with hemifacial paresis. An imaging examination of the brain showed intracranial hemorrhage, and she underwent a craniotomy. We performed histopathological and immunohistochemical (IHC) examinations and diagnosed metastatic ACC with dedifferentiated components. Few ACC cases with dedifferentiated components and with aggressive behavior have been reported in the literature , and to the best of our knowledge, this article is the first English report in Iranian population.