In MBC, the aims of treatment are symptom control and prolongation of survival. Although the debate concerning combination therapy versus sequential single agent continues, targeted biologics, such as trastuzumab, provide a compelling argument for the use of these agents in combination with traditional chemotherapeutics. Trastuzumab combined with chemotherapy offers the possibility of achieving these goals at the price of acceptable toxicity. Its targeted nature has relevant implications in the selection of patients to be treated with this agent.

Also, the integration of trastuzumab in the adjuvant setting has begun to show promise. Trastuzumab combined with chemotherapy results in increased disease-free survival and overall survival when compared with chemotherapy alone. Although methods to assess HER2 status may vary, the test in question must be validated by regular internal and external quality control. Much research needs to be done to determine the appropriate duration of administration to afford maximum benefit and to avoid unnecessary toxicity and expense. Cardiotoxicity mandates accurate evaluation of risk factors and measurement of cardiac function before and during treatment. Mechanisms of trastuzumab resistance, either primary or acquired during treatment, need to be determined in order to further exploit its efficacy with other forms of targeted therapy.

As we enter an era where HER2-positive breast cancer is treated as a distinct entity, the question quickly arises as to whether HER2-positive disease in the presence of trastuzumab behaves the same as HER2-negative disease in the absence of trastuzumab. To date, there are few data on this matter but emerging information suggests that trastuzumab (and potentially lapatinib) radically changes the natural history of HER2-positive MBC. Although women with HER2-positive tumors have historically been thought of as having worse prognosis, the advent of trastuzumab means that they appear to do better in response to chemotherapy than do patients with HER2-negative tumors, exhibiting higher rates of response and improved OS.

Anti-HER therapy has brought significant changes for the treatment of HER2-positive breast cancer patients. Investigating the mechanisms of response will help provide insight into cancer biology. Ongoing clinical trials and translational research are sure to provide illuminating information into further application of this exciting therapeutic approach.

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