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Stickeler, Elmar (3)
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Targeted and Osteo-Oncologic Treatment in Early Breast Cancer: What Is State-of-the-Art and What Might Become so within the Next 5 Years?
In 2014, modern strategies of targeted therapies in the adjuvant setting are mainly focused on anti-human epidermal growth factor receptor 2 (HER2) blockade. For the 15% of HER2-enriched tumors, 1 year of treatment with the monoclonal antibody trastuzumab is the standard of care. All patients, regardless of tumor size, nodal status, or age, profit from therapy with risk reduction rates for recurrence of up to 50%. As a consequence, the current guidelines recommend the use of trastuzumab in these patients if additional risk factors lead to the consideration of adjuvant chemotherapy. The concurrent use with taxane-based chemotherapy is preferred. The concept of dual HER2 blockade – already approved in the metastatic setting – shows also significantly improved efficacy in neoadjuvant trials. Dual blockade with trastuzumab and pertuzumab is approved by the Food and Drug Administration (FDA) for neoadjuvant treatment of HER2-overexpressing tumors. However, until approved in Europe, this treatment approach remains off-label for early breast cancer and study participation is highly recommended. Bisphosphonates (BPs) and denosumab are approved in breast cancer as standard therapy for the treatment of bone metastases. In the adjuvant setting, BPs and denosumab can be given to prevent tumor therapy-induced bone loss. The antineoplastic effect of BPs in the adjuvant setting and its role in the prevention of metastatic disease are still under discussion.
Early breast cancer; Targeted therapy; HER2; Osteo-oncology
Prognostic and Predictive Markers for Treatment Decisions in Early Breast Cancer
Breast cancer clinically represents a heterogeneous disease. Over the last decades, the integration of prognostic and predictive markers in treatment decisions has led to a more individualized and optimized therapy. While prognosis describes the risk of disease recurrence and disease-related death after diagnosis without the influence of therapy, prediction illustrates the probability of efficacy or response of a specific therapeutic measure. The substantial decline in breast cancer mortality seen over the last 20 years is primarily due to the delivery of adjuvant systemic therapy. It is important that clinical decisions are made to minimize overtreatment, under-treatment, and incorrect treatment. Improved understanding of breast cancer biology together with the utilization of classical biomarkers and the identification of new markers or profiles is increasingly defining who should receive cancer therapy and what therapy offers the best efficacy. The molecular targets as the prerequisite for successful concepts of specific therapies like anti-estrogens, antibodies, or small molecules, have therefore high clinical value in regards to prognosis as well as prediction.
Prognosis; Prediction; Early breast cancer; Biomarkers
Immunological Approaches in the Treatment of Metastasized Breast Cancer
A better understanding of tumor biology has led to the development of a number of antibody-based targeted therapies in breast cancer. Several of these newer agents, such as trastuzumab and bevacizumab have demonstrated clinical activity and have improved the treatment of patients with metastatic breast cancer (MBC). Trastuzumab is a monoclonal antibody that binds to the extracellular domain of the HER2 receptor. The addition of trastuzumab to chemotherapy and also to endocrine therapy has enhanced efficacy of treatment. New antibody-based strategies directed against HER2 are under development. These new approaches include pertuzumab, an antibody with a different binding epitope that inhibits dimerization of HER2 with other members of the HER receptor family and TDM1, a trastuzumab-based antibody chemotherapeutic conjugate. Another approach to the treatment of solid tumors is inhibition of angiogenesis. The anti-VEGF antibody bevacizumab has been approved for treatment of MBC. Although the mechanism of action is still under investigation, bevacizumab is tested in other clinical settings such as adjuvant therapy, maintenance therapy, and in combination with both chemotherapy and other targeted agents. In this review, we will summarize the most important studies on trastuzumab and bevacizumab, and describe new antibodies currently under clinical development.
Breast cancer; Metastasis; Antibody; Therapy
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