Currently, there are two major targeted therapy strategies available for the treatment of metastatic breast cancer: anti-her2 therapy and anti-angiogenic therapy.

　　Therapeutic targeting of HER2 with humanized antibodies trastuzumab has proven to be an important component of first-line treatment for patients with HER2+ advanced breast cancer. Particularly, the combination of trastuzumab with taxanes or vinorelbine has been established. The emerging clinical problem is resistance to anti-HER2 therapy. Considering the wide variety of potential mechanisms of resistance, the responsiveness of the individual tumors is probably complex and may differ from case to case. Several studies are ongoing to determine if novel agents could effectively bypass the molecular event responsible for trastuzumab resistance. At present, it is uncertain which is the best option for subsequent therapy upon relapse during or after adjuvant therapy with trastuzumab and subsequent therapies after first-line trastuzumab-based therapy. Second-line capecitabine in combination with lapatinib may be the best choice. However, re-challenge with trastuzumab could be an option, and disease-free interval may also affect the decision. Simultaneously blocking multiple HER family members may be more effective than trastuzumab therapy alone. Rational combination targeting is likely to be the next important step forward in the treatment of HER2-positive breast cancer. Approximately half of the patients with HER2-positive breast cancer are also positive for hormone receptors. Evidence of cross talk between HER2- and ER-signaling pathways suggests that combined treatment with HER2 blockade and hormonal therapy may offer clinical advantages beyond those provided by hormonal therapy alone in ER+/HER2+ disease. Combined therapy with trastuzumab or lapatinib plus an aromatase inhibitor significantly improves progression-free survival, response rates, and clinical benefits when compared with aromatase inhibitor monotherapy in postmenopausal women. Nonetheless, combination chemotherapy with HER2-directed therapy should be the first-line treatment option in patients with good performance status, visceral disease or rapid progression.

　　Increased levels of vascular endothelial growth factor (VEGF) have been associated with a poor prognosis for patients with breast cancer. In addition to its prognostic role, VEGF is also a validated target in the treatment of this disease. Bevacizumab, an anti-VEGF antibody, has demonstrated significant clinical benefit in several solid tumors, including breast cancer. Its use in combination with chemotherapeutic agents including paclitaxel, docetaxel, capecitabine, or anthracyclines has prolonged progression-free survival and increased response rates in the first-line treatment of patients with metastatic, HER2-negative breast cancer.