Recombinant Humanized Monoclonal Antibody Trastuzumab for the Treatment of Metastatic Breast Cancer with Tumors Overexpressing the HER2/neu Proto-Oncogene : A Systematic Review
Breast cancer is viewed as a major medical challenge with significant public health and societal consequences. Although there have been major advances in the biological and clinical understandings of breast cancer and dramatic progresses in the treatment, this medical challenge still persists and has become increasingly complex. Metastatic breast cancer is considered as an incurable disease; median survival is 2-3 years. The HER2 proto-oncogene encodes an 185 kDa phosphoglycoprotein (P185HER2/neu), which exhibits general homology to epidermal growth factor receptor (EGRF). Its overexpression results in increased signaling via the ras-MAPK pathway and, thus, cellular proliferation. Overexpression of HER2 occurs in 25% of breast cancer patients, and is associated with aggressive tumor behavior and a poor prognosis, including advanced stage, involve-ment of axillary lymph nodes, absence of estrogen and progesterone recep-tors, increased S-phase fraction and high nuclear grade. Trastuzumab approved for monotherapy or combination therapy with paclitaxel is a recombinant "humanized" monoclonal antibody (rhuMAb) that selectively binds to HER2/neu on the cell surface resulting in receptor down-regulation and killing of cells by the immune system. The objectives of the review were to evaluate the clinical effectiveness and cost-effectiveness of trastuzumab in the management of advanced breast cancer. Only randomised controlled trials of trastuzumab alone, or in combination with other agents, versus systemic therapy without trastuzumab, were initially considered in the assessment of clinical effectiveness. The assessment of cost effectiveness includes only full economic evaluations.
Dieser Eintrag ist Teil der Universitätsbibliographie.
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