Integrating biological agents into systemic therapy of breast cancer: trastuzumab, lapatinib, bevacizumab

Abstract

Biologic agents represent an already proven addition in the armamentarium of anticancer weapons. Anti-HER2 therapy was the first to demonstrate survival benefit by associating a targeted agent to cytotoxic chemotherapy. Four major adjuvant trials--Herceptin Adjuvant (HERA), National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31, North Central Cancer Treatment Group (NCCTG) N9831, and Breast Cancer International Research Group (BCIRG) 006--including more than 13,000 women with HER-2-positive early breast cancer, have investigated different adjuvant treatment approaches with trastuzumab. These trials have shown that trastuzumab reduces the 3-year risk of recurrence by about half in this patient population. Accurate testing for HER2 amplification/overexpression is essential before treatment initiation. Patients progressing while on combined chemotherapy and trastuzumab may still benefit from continuation of trastuzumab with other agents; evidence also supports the use of the capecitabine/lapatinib combination in this setting, which improves response and time to further tumor progression. Antiangiogenic therapy with bevacizumab in association with weekly paclitaxel improves disease-free survival for metastatic breast cancer patients. Future studies will provide much needed data on predicting response to biologic therapies, revealing the mechanisms of resistance to such therapies and maximizing the patient's benefit.