Beyond trastuzumab: New treatment options for HER2-positive breast cancer

In recent years, there has been a wide range of treatment options for patients with metastatic HER2-positive breast cancer, resulting in the highest life expectancy for these patients among all subtypes. The addition of pertuzumab to trastuzumab and docetaxel has been shown to increase overall survival and is therefore recognized as the standard first-line treatment. The most optimal second-line treatment option is trastuzumab emtansine. In addition, various combinations of cytostatics and anti HER2 targeting agents can be used. The choice of treatment options in heavily pretreated patients is of great interest. If they have not previously received pertuzumab, is it worth to use it and which combination is the best? One possible option is the combination of eribulin with the dual anti-HER2 blockade with trastuzumab and pertuzumab. Eribulin is an anti-microtubule agent that irreversibly blocks mitosis. In addition, it has non-mitotic effects – in vivo and in vitro experiments demonstrated its ability to restore normal tumor vascularization, reduce the area of hypoxia and, as a consequence, decrease tumor cells migration and invasion. This article represents a clinical case of the use of eribulin with double anti-HER2 blockade in the 6th line of treatment in a patient with metastatic HER2-positive breast cancer. Long-term control of the disease (within 2 years) with a satisfactory quality of life has been demonstrated.

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Systemic Treatment Options for HER2-Positive Breast Cancer Patients with Brain Metastases beyond Trastuzumab: A Literature Review

Breast Care ◽

10.1159/000467387 ◽

2017 ◽

Vol 12 (3) ◽

pp. 168-171 ◽

Cited By ~ 12

Author(s):

Elena Laakmann ◽

Volkmar Müller ◽

Marcus Schmidt ◽

Isabell Witzel

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Cancer Patients ◽

Systemic Treatment ◽

Treatment Options ◽

Cytotoxic Agents ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

Background: The incidence of brain metastases (BM) in breast cancer patients has increased. Many retrospective analyses have shown that first-line treatment with trastuzumab prolongs survival in patients with HER2-positive BM. In contrast, the evidence for other therapies targeting HER2 for patients with BM is rare. Methods: The aim of this review is to update the reader about current systemic treatment options in patients with HER2-positive metastatic breast cancer with BM who had already received trastuzumab. A literature search was performed in the PubMed database in June 2016. 30 relevant reports concerning the efficacy of trastuzumab emtansine (T-DM1), lapatinib and its combination with other cytotoxic agents, pertuzumab and novel HER2-targeting substances were identified. Results: There is limited but promising evidence for the use of T-DM1 and pertuzumab in the treatment of BM. Up to now, most reported studies used lapatinib as treatment of HER2-positive breast cancer with BM, a treatment with only a modest effect and a high toxicity profile. The combination of lapatinib with cytotoxic agents seems to result in better response rates. Conclusion: Further prospective investigations are needed to investigate the efficacy of the established and novel HER2-targeting agents on BM in HER2-positive breast cancer patients.

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Targeted Therapies in HER2-Positive Breast Cancer - a Systematic Review

Breast Care ◽

10.1159/000431029 ◽

2015 ◽

Vol 10 (3) ◽

pp. 173-178 ◽

Cited By ~ 19

Author(s):

Amelie Schramm ◽

Nikolaus De Gregorio ◽

Peter Widschwendter ◽

Visnja Fink ◽

Jens Huober

Keyword(s):

Breast Cancer ◽

Targeted Therapies ◽

Treatment Options ◽

Treatment Strategies ◽

Her2 Overexpression ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Increased Risk ◽

Positive Breast Cancer

About 20% of all breast cancer patients have a human epidermal growth factor receptor 2 (HER2)-positive breast tumor. This entity underwent an impressive change in prognosis, with notable improvement of progression-free survival and overall survival. Due to more aggressive tumors and no specific therapy, HER2 overexpression was historically seen as a negative prognostic marker, with worse prognosis and increased risk of recurrent disease. Trastuzumab, the first anti-HER2 antibody, revolutionized the systemic therapy options in HER2-positive breast cancer and initiated several targeted therapies and more personalized treatment strategies. Over the years, multiple HER2-targeting drugs stepped into clinical practice, for the curative as well as the metastatic situation. This review summarizes the targeted treatment options in HER2-positive breast cancer and their current impact in the clinical routine. Results of the most outstanding trials in HER2-targeted therapies and important ongoing trials are subsequently described for an up-to-date overview.

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HER2-directed therapy: current treatment options for HER2-positive breast cancer

Breast Cancer ◽

10.1007/s12282-015-0587-x ◽

2015 ◽

Vol 22 (2) ◽

pp. 101-116 ◽

Cited By ~ 88

Author(s):

Shahid Ahmed ◽

Amer Sami ◽

Jim Xiang

Keyword(s):

Breast Cancer ◽

Treatment Options ◽

Current Treatment ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

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

Geburtshilfe und Frauenheilkunde ◽

10.1055/a-1471-4063 ◽

2021 ◽

Vol 81 (06) ◽

pp. 666-678

Author(s):

Diana Lüftner ◽

Matthias Peipp

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Treatment Options ◽

Metastatic Breast ◽

Antibody Engineering ◽

Antibody Drug Conjugate ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

The Us ◽

Positive Breast Cancer

AbstractDespite 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.

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