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      Metastatic Salivary Duct Carcinoma with ERBB2 Amplification and Sequential Response to Ado-Trastuzumab Emtansine and Neratinib: A Case Report

      case-report

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          Abstract

          Introduction

          Salivary duct carcinoma (SDC) is an aggressive and rare subtype of salivary gland carcinoma. Surgical excision and radiotherapy are standard of care for early cancer. Chemotherapies with taxanes and platinum show overall response rates between 39% and 50%. SDCs are often associated with an overexpression of the androgen receptor (AR) and HER2/neu which have recently become druggable targets.

          Case Presentation

          Here, we report on an 84-year-old male patient with metastatic SDC of the right parotid gland. In 2017, he underwent a right total parotidectomy, a right neck dissection, and an infratemporal fossa clearance followed by 6 weeks of radiotherapy. In 2018, due to metastatic spread in the lungs, bones, and pararenal gland, a pathological workup of the tumor tissue was performed and revealed both AR and HER2 overexpression, respectively. Consequently, he underwent androgen deprivation therapy and, due to asymptomatic progression, sequentially human epidermal growth factor receptor 2 (HER-2)-targeted therapy with ado-trastuzumab emtansine and neratinib, which led to stable disease during the course of about 18 months. The electronically captured patient-reported outcome had demonstrated a good tolerance of all three therapeutic lines.

          Conclusion

          In conclusion, since effective standard therapeutic treatment options for SDC may often not be tolerable in older patients, the implementation of personalized and adaptive treatments, especially in patients with rare tumor types, might offer valuable treatment options.

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          Most cited references17

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          The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis.

          M Moasser (2007)
          The year 2007 marks exactly two decades since Human Epidermal Growth Factor Receptor-2 (HER2) was functionally implicated in the pathogenesis of human breast cancer. This finding established the HER2 oncogene hypothesis for the development of some human cancers. The subsequent two decades have brought about an explosion of information about the biology of HER2 and the HER family. An abundance of experimental evidence now solidly supports the HER2 oncogene hypothesis and etiologically links amplification of the HER2 gene locus with human cancer pathogenesis. The molecular mechanisms underlying HER2 tumorigenesis appear to be complex and a unified mechanistic model of HER2-induced transformation has not emerged. Numerous hypotheses implicating diverse transforming pathways have been proposed and are individually supported by experimental models and HER2 may indeed induce cell transformation through multiple mechanisms. Here I review the evidence supporting the oncogenic function of HER2, the mechanisms that are felt to mediate its oncogenic functions, and the evidence that links the experimental evidence with human cancer pathogenesis.
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            Evolving concepts in HER2 evaluation in breast cancer: heterogeneity, HER2-low carcinomas and beyond

            The human epidermal growth factor receptor 2 (HER2) is a well-known negative prognostic factor in breast cancer and a target of the monoclonal antibody trastuzumab as well as of other anti-HER2 compounds. Pioneering works on HER2-positive breast cancer in the 90s' launched a new era in clinical research and oncology practice that has reshaped the natural history of this disease. In diagnostic pathology the HER2 status is routinely assessed by using a combination of immunohistochemistry (IHC, to evaluate HER2 protein expression levels) and in situ hybridization (ISH, to assess HER2 gene status). For this purpose, international recommendations have been developed by a consensus of experts in the field, which have changed over the years according to new experimental and clinical data. In this review article we will document the changes that have contributed to a better evaluation of the HER2 status in clinical practice, furthermore we will discuss HER2 heterogeneity defined by IHC and ISH as well as by transcriptomic analysis and we will critically describe the complexity of HER2 equivocal results. Finally, we will introduce the clinical impact of HER2 mutations and we will define the upcoming category of HER2-low breast cancer with respect to emerging clinical data on the efficacy of specific anti-HER2 agents in subgroups of breast carcinomas lacking the classical oncogene addition dictated by HER2 amplification.
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              Beyond EGFR, ALK and ROS1: Current evidence and future perspectives on newly targetable oncogenic drivers in lung adenocarcinoma

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                Author and article information

                Journal
                Case Rep Oncol
                Case Rep Oncol
                CRO
                CRO
                Case Reports in Oncology
                S. Karger AG (Basel, Switzerland )
                1662-6575
                29 November 2023
                Jan-Dec 2023
                29 November 2023
                : 16
                : 1
                : 1500-1507
                Affiliations
                [a ]University of Zurich, Zurich, Switzerland
                [b ]MRI Stadelhofen, Zurich, Switzerland
                [c ]Swiss Ablation, Zurich, Switzerland
                [d ]Pathologie Institut Enge, Zurich, Switzerland
                [e ]Mobile Health, Zurich, Switzerland
                [f ]BrustZentrum Zürichsee, Horgen, Switzerland
                Author notes
                Correspondence to: Andreas Trojan, andreas.trojan@ 123456mobilehealth.ch
                Article
                535097
                10.1159/000535097
                10686627
                38033416
                fd3c2465-2805-47e4-8efd-10559a6cf547
                © 2023 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC) ( http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                : 16 October 2023
                : 6 November 2023
                : 2023
                Page count
                Figures: 3, Tables: 1, References: 17, Pages: 8
                Funding
                The Foundation Swiss Tumor Institute has supported the master’s thesis with a restricted grant.
                Categories
                Case Report

                Oncology & Radiotherapy
                erbb2,salivary duct carcinoma,neratinib,electronically captured patient-reported outcomes,case report

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