Integration of novel targeted therapies into the systemic treatment of breast cancer - a review

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 inpatients with metastatic breast cancer whereas, over the last 2 years studies incorporating trastuzumab insequence to or concurrently with taxane-based chemotherapy in the adjuvant setting demonstrated a considerable benefit in this subset, with the results of longer follow-up regarding long-term outcome and late toxicities expected over the forth coming 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.