Perspectives of immunotherapy in metastatic breast cancer

Further improvements in the treatment of breast cancer can be expected with a better understanding of its pathophysiology and through biologically-oriented therapeutic interventions, as well as better identification of patient populations likely to benefit from specific therapies. Trastuzumab (Herceptin) is the first biological modifier, showing significant activity in patients with advanced breast cancer who exhibit HER-2/neu gene amplification and/or protein overexpression. Trastuzumab is approved for use in combination with paclitaxel or docetaxel as first-line chemotherapy. Combinations of a taxane, a platinum salt and trastuzumab are feasible and active and have proven an increased survival advantage. This is in addition to the benefit that has been shown for Herceptin in combination with monochemotherapy alone. Several groups have demonstated the ratio of serum HER-2/neu levels prior to initiation of Herceptin treatment to levels at the time of re-staging examination to be significantly higher in patients with a significant benefit from therapy as compared to patients with progressive disease. As a result of the survival improvements in the metastatic setting, Herceptin was quickly entered into development trials for adjuvant treatment. The significant cardiac toxicity that has been observed with trastuzumab/anthracycline combinations has led to two main strategies for integrating trastuzumab in the adjuvant setting: either the addition of trastuzumab to mostly anthracycline-based programs in a sequential approach, or the biologically-oriented strategy based on synergism between trastuzumab and chemotherapy agents including platinum compounds. Last but not least, the most important prerequisite for the optimal efficacy of Herceptin-based therapy remains a very strict selection of those patients with tumours that have HER-2/neu over-expression.