
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.