title: Integration of novel targeted therapies into the systemic treatment of breast cancer--a review.
abstract: Over the last few years it has been anticipated that molecularly targeted agents can provide substantial improvement in the treatment of breast cancer. The most illustrative paradigm has been that of trastuzumab (Herceptin), a humanized monoclonal antibody against the HER2 oncoprotein overexpressed in 25% of breast cancers. Trastuzumab when combined with standard cytotoxic chemotherapy improved the outcome and survival in patients with metastatic breast cancer, whereas, over the last 2 years studies incorporating trastuzumab in sequence to or concurrently with taxane-based chemotherapy in the adjuvant setting demonstrated a considerable benefi t in this subset, with the results of longer follow-up regarding long-term outcome and late toxicities expected over the forthcoming years. Moreover, the prognostic and predictive value of topoisomerase IIa (Topo IIa) overexpression in these subgroups with respect to anthracycline treatment has been extensively discussed and analysed. Other inhibitors of both HER1/HER2 have recently been introduced with promising results and results of ongoing studies are awaited with great interest. A recently anticipated target in advanced breast cancer has been the pathway of angiogenesis; first a humanized monoclonal antibody-bevacizumab (Avastin)- has demonstrated encouraging results when combined with chemotherapy in pretreated HER2-negative advanced breast cancer, while combinations with trastuzumab+/-chemotherapy are currently examined in HER2-overexpressing breast cancer. Furthermore, as novel molecular pathways relevant to breast cancer biology are explored, it is expected that a whole array of targeted agents will be tested in combination or in sequence to standard chemotherapy with the aim to improve outcome of high-risk breast cancer patients.
authors.affiliation: Department of Medicine, 2nd Division of Medical Oncology, Metaxa Cancer Hospital, Piraeus, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Tsakonas
authors.forename: C
authors.initials: C
authors.lastname: Kosmas
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000187:drug effects; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000187:drug effects; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases