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Breast Disease pp 463-494 | Cite as

Treatment of HER2-Overexpressing Metastatic Breast Cancer

  • Adnan Aydiner
Chapter

Abstract

Metastatic breast cancer (MBC) overexpressing human epidermal growth factor receptor-2 (HER2) once had an overall worse prognosis, but therapies targeting HER2 have altered the natural course of HER2-positive disease. The initial success of trastuzumab in improving survival rates led to the clinical development of lapatinib, pertuzumab, and trastuzumab emtansine (T-DM1). HER2 protein overexpression and/or gene amplification remain the most important predictive factors for response to HER2-targeted therapies. The optimal duration of chemotherapy (CT) is at least 4–6 months (or longer) and/or to the time of maximal response, depending on toxicity and the absence of progression. HER2-targeted therapy continues until progression or unacceptable toxicity. For patients with estrogen receptor–positive/progesterone receptor–positive breast cancer who are not good candidates for CT or wish to avoid the toxicity of CT, initial hormone therapy in combination with HER2-targeted therapy is a reasonable option. For patients who relapse and were previously treated with adjuvant anti-HER2 therapy, the resumption of systemic treatment that includes HER2 blockade is recommended. As in the first-line setting, multiple choices are available for second- and third-line therapies. Successful targeting of HER2 has improved outcomes in HER2-positive breast cancer, but treatment resistance and brain metastases remain a problem. Ongoing studies are evaluating novel therapeutic approaches to overcome primary and secondary drug resistance in HER2-positive tumors.

Keywords

HER2  Trastuzumab  Pertuzumab  T-DM1  Lapatinib  Trastuzumab emtansine  PI3K  PI3KCA  PTEN  Drug resistance  Antibody-drug conjugate  Everolimus  mTOR  Afatinib  Metastatic  EGFR  HER3  Cardiotoxicity  Leptomeningeal metastases  Brain metastases  RECIST 

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Adnan Aydiner
    • 1
  1. 1.Oncology Institute, Istanbul Medical FacultyIstanbul UniversityIstanbulTurkey

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