CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2021; 81(06): 666-678
DOI: 10.1055/a-1471-4063
GebFra Science

New Therapeutic Strategies in Advanced Nonoperable or Metastatic HER2-positive Breast Cancer

Article in several languages: English | deutsch
Diana Lüftner
1   Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Charité, Universitätsmedizin Berlin, Berlin, Germany
Matthias Peipp
2   Sektion für Stammzelltransplantation und Immuntherapie, Dr. Mildred-Scheel-Haus, Universitätsklinikum Schleswig-Holstein, Kiel, Germany
› Author Affiliations


Despite therapeutic gains in the treatment of HER2-positive (HER2: human epidermal growth factor receptor 2) advanced/metastatic breast cancer, there remains an urgent need for more effective treatment options. At present, there is no definitive approved standard therapy beyond second-line treatment. One of the major challenges is overcoming treatment resistance. Depending on the underlying resistance mechanism, different strategies are being pursued for new innovative treatment concepts in HER2-positive breast cancer. Specifically designed antibodies for targeted therapy are one important focus to successfully meet these challenges. Trastuzumab deruxtecan (T-DXd, DS-8201a), an optimised antibody drug conjugate (ADC) is in clinical trials, showing promising outcomes in patients with advanced, nonoperable or metastatic HER2-positive breast cancer who had already undergone intensive prior treatment. Based on this data, T-DXd has already been approved in the US and Japan for HER2-positive advanced nonoperable and metastatic breast cancer – in the US after at least two prior anti-HER2 targeted treatment lines and in Japan after prior chemotherapy. T-DXd represents successful “antibody engineering”. Since the beginning of the year, T-DXd has also been approved in Europe as monotherapy for inoperable or metastatic HER2-positive breast cancer in patients who are pretreated with at least two anti-HER2 directed therapies. This paper presents strategies for improving treatment options in advanced nonoperable and metastatic HER2-positive breast cancer, with the development of T-DXd as an example.

Publication History

Received: 20 December 2020

Accepted: 27 March 2021

Publication Date:
21 June 2021 (online)

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