Current paradigms for the use of HER2-targeted therapy in early-stage breast cancer

Results are now available from 6 trials randomizing > 14,000 women with HER2-positive early breast cancer to trastuzumab versus non-trastuzumab-based adjuvant chemotherapy. Aside from the recently presented PACS 04 trial, these studies demonstrate remarkably consistent results: the addition of trastuzumab reduces recurrence by approximately 50% and improves overall survival by 30%, irrespective of tumor size, nodal status, schedule of administration, and type of chemotherapy administered. There remain many unanswered questions regarding optimal adjuvant trastuzumab use, including the relationship between trastuzumab efficacy and markers of HER2 assessment (HER2 protein expression, gene copy number, and chromosome 17 polysomy); the selection of patients for non-anthracycline-based chemotherapy; the decision to administer trastuzumab in a sequential or concurrent manner with chemotherapy; and the minimal effective duration of trastuzumab required for adjuvant therapy. Future studies with novel anti-HER2 strategies will prospectively evaluate biomarkers in an effort to further improve the outcome of women diagnosed with HER2-positive disease.