State of the art management of locally advanced breast cancer

Multimodality therapy has an established role in the management of patients with locally advanced breast cancer (LABC). Induction chemotherapy permits optimal local control with less radical surgical and therapeutic intervention, although its impact in overall survival is still unclear. Optimal sequencing of surgery and radiation therapy is based on information from selected phase II trials, but definitive data are not available to determine which sequence is best; therefore, treatment should continue to be individualized. The major obstacle to long-term survival for patients with locally advanced breast cancer is the development of distant metastases. Therefore, the development of more effective systemic therapies is required. Systemic therapy has traditionally involved chemotherapy followed by hormonal agents depending on receptor status. New cytotoxic agents with demonstrated antitumor efficacy against metastatic breast cancer have been recently developed (the taxanes in particular), and are starting to be incorporated in clinical studies targeted to patients with locally advanced breast cancer. High-dose chemotherapy requiring stem cell rescue is also an area under study. However, preliminary data from a recently completed Dutch randomized trial comparing standard dose vs. High dose chemotherapy plus stem cell rescue in patients with locally advanced breast cancer do not demonstrate a statistically significant improvement in overall survival, with 3 years of median follow up. Further studies to optimize the components of high-dose treatments, to improve efficacy and decrease morbidity will be necessary before concluding that this approach offers an improved option to standard chemotherapy-dose regimens. The utilization of monoclonal antibodies against breast cancer related antigens; either individually or as vehicles to deliver chemotherapy, radioisotopes or natural toxins is another area starting to be investigated. The ultimate impact of the incorporation of these newer agents (as part of multimodality treatments) in improving the overall survival, long term disease free survival, local control and quality of life requires intense investigation. LABC also affords a special research opportunity; that is, the ability to obtain primary tissue before and after chemotherapy to correlate with response, prognosis and survival. The evaluation of biological parameters which could be predictors for response and survival while patients receive state of the art therapy should ultimately lead to significant improvements in the management and survival of patients with locally advanced breast cancer.