Relapsed and De Novo Metastatic HER2-positive Breast Cancer Treated With Trastuzumab: Tumor Genotypes and Clinical Measures Associated With Patient Outcome

2019 ◽  
Vol 19 (2) ◽  
pp. 113-125.e4 ◽  
Author(s):  
Vassiliki Kotoula ◽  
Kalliopi Tsakiri ◽  
Georgia-Angeliki Koliou ◽  
Georgios Lazaridis ◽  
Kyriaki Papadopoulou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Patient Outcome ◽  
De Novo ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Clinical Measures ◽  
Positive Breast Cancer

scholarly journals HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance

2019 ◽  
Vol 11 ◽  
pp. 175883591983351 ◽  
Author(s):  
Sonia Pernas ◽  
Sara M. Tolaney
Keyword(s):  
Breast Cancer ◽  
Kinase Inhibitors ◽  
De Novo ◽  
Checkpoint Inhibitors ◽  
Acquired Resistance ◽  
Mtor Inhibitors ◽  
Therapy Resistance ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

The introduction of anti-HER2 therapies to the treatment of patients with HER2-positive breast cancer has led to dramatic improvements in survival in both early and advanced settings. Despite this breakthrough, nearly all patients with metastatic HER2-positive breast cancer eventually progress on anti-HER2 therapy due to de novo or acquired resistance. A better understanding not only of the underlying mechanisms of HER2 therapy resistance but of tumor heterogeneity as well as the host and tumor microenvironment is essential for the development of new strategies to further improve patient outcomes. One strategy has focused on inhibiting the HER2 signaling pathway more effectively with dual-blockade approaches and developing improved anti-HER2 therapies like antibody–drug conjugates, new anti-HER2 antibodies, bispecific antibodies, or novel tyrosine kinase inhibitors that might replace or be used in addition to some of the current anti-HER2 treatments. Combinations of anti-HER2 therapy with other agents like immune checkpoint inhibitors, CDK4/6 inhibitors, and PI3K/AKT/mTOR inhibitors are also being extensively evaluated in clinical trials. These add-on strategies of combining optimized targeted therapies could potentially improve outcomes for patients with HER2-positive breast cancer but may also allow de-escalation of treatment in some patients, potentially sparing some from unnecessary treatments, and their related toxicities and costs.

scholarly journals Hormonal treatment combined with targeted therapies in endocrine-responsive and HER2-positive metastatic breast cancer

2019 ◽  
Vol 11 ◽  
pp. 175883591989410 ◽  
Author(s):  
Emilia Montagna ◽  
Marco Colleoni
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Signaling Pathways ◽  
Targeted Therapies ◽  
De Novo ◽  
Current Knowledge ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Approximately 50% of HER2 positive breast cancer cases are also estrogen receptor (ER) positive. Data supports a role for close cross-talk between the ER and HER2 signaling pathways as an important contributor to the development of de novo or acquired resistance to hormone therapies. Therefore a strategy that simultaneously blocks both signaling pathways is a reasonable approach to prevent or overcome either endocrine or anti-HER2 therapy resistance. Moreover, preclinical data support the idea that PI3K inhibitors and CDK4/6 could be an attractive target that functions downstream of both ER and HER2 pathways. We conducted a literature review of the results of phase II and III studies testing targeted therapies in metastatic breast cancer with HER2-positive and hormonal-receptor-positive disease. The analyses included efficacy and toxicity data from earlier studies with a single anti-HER2 drug combined with hormonal therapy up to more recent studies testing new molecules targeting these signaling pathways. The aims of this review are to summarize current knowledge and to discuss research development including the possibility to spare chemotherapy in this subgroup of HER2-positive breast cancer patients.

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