Disease Background

The National Cancer Institute estimates 215,990 new cases of breast cancer diagnosis for the year 2004 in the United States with 40,110 disease related deaths (http://www.nci.nih.gov/statistics). Although widespread screening to detect breast cancer at an early stage is employed today throughout America by using scheduled mammography, clinical breast examination, or both, it is still uncertain whether these measures indeed will decrease breast cancer mortality. The existence of such a benefit is uncertain mainly because of the inconsistency between studies. Therefore, it is expected that in the foreseeable future, advanced or metastatic breast cancer will remain a significant health problem in the US and worldwide.

In general, survival is dependent on the stage of the disease at the time of initial diagnosis but also on other tumor specific molecular characteristics. Although multimodality adjuvant and neo-adjuvant therapy has improved outcomes for earlier stage disease, unfortunately many breast cancers, especially locally advanced or stage III still will progress to metastatic or stage IV disease. The major improvement currently available to breast cancer patients today is the use of pre-surgery chemotherapy and radiation therapy. This stage of the disease is incurable with any kind of conventional treatment, as it only marginally impacts the overall survival. Median survival for de novo diagnosed stage IV breast cancer is between two and three years despite treatment, as various clinical trials have shown. Life expectancy for recurrent cancer presenting as stage IV following previous treatment given as adjuvant or neo-adjuvant therapy is even shorter, mainly because active therapies have already been used and may no longer be active upon their reintroduction. Although estrogen and/or progesterone receptor positive cancers often respond to repeated hormonal manipulations, the therapeutic benefit is often short-lived. The most activity chemotherapeutic compounds for breast cancer are anthracyclines and taxanes. Some tumors expressing Her2-neu may respond temporarily to a targeted monoclonal antibody, Herceptin. Once these compounds have been used and the disease has become refractory, prognosis is poor and considered to be less than one-year median survival.