Management of HER-2/neu-positive metastatic breast cancer

We reviewed therapies for the management of HER2-overexpressing metastatic breast cancer. HER2-overexpressing breast cancers have a distinctive molecular signal and distinctive clinical characteristics. They are associated with an adverse prognosis, relative resistance to certain types of therapies (i.e. tamoxifen), and responsiveness to anthracyclines and taxanes. Anti-HER2 therapies such as trastuzumab and lapatinib have revolutionised the treatment of breast cancer and can dramatically improve outcomes in women with HER2-overexpressing metastatic breast cancer. Response to these targeted agents is improved when used in combination with cytotoxic agents such as anthracyclines and taxanes. However, there is an approximate 13% (taxanes) to 27% (conventional anthracyclines) risk of cardiotoxicity with these combinations. The novel anthracycline, pegylated liposomal doxorubicin, shows efficacy similar to that of conventional doxorubicin and may offer significantly less cardiotoxicity; this should be confirmed in phase III clinical trials. Lapatinib is an oral small molecule targeting HER2 with promising antitumour activity in the metastatic setting and a potential for reduced cardiotoxicity as compared with trastuzumab. Neoadjuvant as well adjuvant trials involving lapatinib, trastuzumab or their combination have started recrutiment worldwide.