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

Breast Care ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. 173-178 ◽  
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.

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

Breast Care ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. 168-171 ◽  
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.

scholarly journals Somatic Mutations in HER2 and Implications for Current Treatment Paradigms in HER2-Positive Breast Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Maria Gaibar ◽  
Laura Beltrán ◽  
Alicia Romero-Lorca ◽  
Ana Fernández-Santander ◽  
Apolonia Novillo
Keyword(s):  
Breast Cancer ◽  
Somatic Mutations ◽  
Tyrosine Kinase Domain ◽  
Her2 Overexpression ◽  
Breast Cancer Patients ◽  
Trastuzumab Resistance ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

In one of every four or five cases of breast cancer, the human epidermal growth factor receptor-2 (HER2) gene is overexpressed. These carcinomas are known as HER2-positive. HER2 overexpression is linked to an aggressive phenotype and a lower rate of disease-free and overall survival. Drugs such as trastuzumab, pertuzumab, lapatinib, neratinib, and the more recent afatinib target the deregulation of HER2 expression. Some authors have attributed somatic mutations in HER2, a role in resistance to anti-HER2 therapy as differential regulation of HER2 has been observed among patients. Recently, studies in metastatic ER + tumors suggest that some HER2 mutations emerge as a mechanism of acquired resistance to endocrine therapy. In an effort to identify possible biomarkers of the efficacy of anti-HER2 therapy, we here review the known single-nucleotide polymorphisms (SNPs) of the HER2 gene found in HER2-positive breast cancer patients and their relationship with clinical outcomes. Information was recompiled on 11 somatic HER2 SNPs. Seven polymorphisms are located in the tyrosine kinase domain region of the gene contrasting with the low number of mutations found in extracellular and transmembrane areas. HER2-positive patients carrying S310F, S310Y, R678Q, D769H, or I767M mutations seem good candidates for anti-HER2 therapy as they show favorable outcomes and a good response to current pharmacological treatments. Carrying the L755S or D769Y mutation could also confer benefits when receiving neratinib or afatinib. By contrast, patients with mutations L755S, V842I, K753I, or D769Y do not seem to benefit from trastuzumab. Resistance to lapatinib has been reported in patients with L755S, V842I, and K753I. These data suggest that exploring HER2 SNPs in each patient could help individualize anti-HER2 therapies. Advances in our understanding of the genetics of the HER2 gene and its relations with the efficacy of anti-HER2 treatments are needed to improve the outcomes of patients with this aggressive breast cancer.

scholarly journals Adverse Events of Trastuzumab Emtansine (T-DM1) in the Treatment of HER2-Positive Breast Cancer Patients

Breast Care ◽  
2017 ◽  
Vol 12 (6) ◽  
pp. 401-408 ◽  
Author(s):  
Lidia Kowalczyk ◽  
Rupert Bartsch ◽  
Christian F. Singer ◽  
Alex Farr
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Targeted Therapies ◽  
Kinase Inhibitor ◽  
Trastuzumab Emtansine ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Anti Tumor Activity ◽  
Positive Breast Cancer

The human epidermal growth factor receptor 2 (HER2) is commonly associated with poor prognosis and is overexpressed in approximately 15-20% of all breast cancers. The introduction of HER2-targeted therapies led to significant improvement in the prognosis of patients with HER2-positive breast cancer, for both early and advanced disease. These targeted therapies include the antibodies trastzumab and pertuzumab, the tyrosine kinase inhibitor lapatinib, and the antibody-drug conjugate trastuzumab emtansine (T-DM1). T-DM1 combines the anti-tumor activity of trastuzumab with that of DM1, a highly potent derivative of the anti-microtubule agent maytansine, resulting in increased anti-tumor activity. Notably, this agent has been demonstrated to be safe and is associated with low toxicity rates. However, maytansinoid, the cytotoxic component of T-DM1, does have the potential to induce various adverse events, particularly radiation necrosis, when used in combination with stereotactic radiosurgery. In this review, we aimed to summarize the current literature regarding T-DM1 safety and toxicity, with special emphasis on the existing landmark studies.

scholarly journals Brain Metastases in HER2-Positive Breast Cancer: Current and Novel Treatment Strategies

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2927
Author(s):  
Alejandro Garcia-Alvarez ◽  
Andri Papakonstantinou ◽  
Mafalda Oliveira
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Treatment Strategies ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Novel Treatment ◽  
Increased Risk ◽  
Novel Treatment Strategies ◽  
Positive Breast Cancer

Development of brain metastases can occur in up to 30–50% of patients with breast cancer, representing a significant impact on an individual patient in terms of survival and quality of life. Patients with HER2-positive breast cancer have an increased risk of developing brain metastases; however, screening for brain metastases is not currently recommended due to the lack of robust evidence to support survival benefit. In recent years, several novel anti-HER2 agents have led to significant improvements in the outcomes of HER2-positive metastatic breast cancer. Despite these advances, brain and leptomeningeal metastases from HER2-positive breast cancer remain a significant cause of morbidity and mortality, and their optimal management remains an unmet need. This review presents an update on the current and novel treatment strategies for patients with brain metastases from HER2-positive breast cancer and discusses the open questions in the field.

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