Targeted immunoediting of critical pathways responsible for breast cancer development: treatment of early breast cancer using HER-2/neu pulsed dendritic cells
Multiple genetic targets have been discovered that may help fight breast cancer, including BRCA, estrogen receptors, and HER-2/neu, all of which have been known to predict the severity of disease, recurrence and overall survival. Developing novel therapies that target these specific genetic variances may be extremely beneficial in preventing breast cancer for many women.
In this study, researchers investigated a potential vaccine that targets HER-2/neu over-expression in early stage breast cancer, known as DCIS (ductal carcinomas in situ, or early stage cancer formation in the breast's milk ducts). It is estimated at 50-60 percent of DCIS is directly related to HER-2/neu over-expression.
Patients with HER-2/neu overexpression were given a therapy of dendritic cells (DC, which work with the B- and T-cells to trigger immune responses) that were treated with HER-2/neu to evoke an immune response. The participants received four weekly vaccinations into normal lymph nodes in their groins and were evaluated both pre- and po st-vaccination for immune response, level of HER-2/neu expression, and cell infiltrates.
The researchers found that most patients responded well to the vaccination. Nearly all patients (11 of 12) exhibited an initial immune response (shown by the presence of anti-HER-2/neu specific CD4+ T cells), and many of the patients developed protein antibodies to fight the HER-2/neu cells. Patients began to build up reserves of white blood cells following treatment and seemed to show long-term immune responses to HER-2/neu as a result of the therapy. Of the 12 study participants, six showed markedly reduced levels of HER-2/neu expression after the vaccination, and as a result, the investigators also noted an improvement in their severity of their disease.
"The results demonstrate for the first time that this DC vaccination may have significant clinical activity against certain types of breast cancer," said Brian J. Czerniecki, M.D., of the University of Pennsylvania, and lead author of the study. "We are confident that targeted treatment with this vaccine may effectively fight not only DCIS, but may extend to prevention of breast cancer entirely."
According to the American Cancer Society, approximately 200,000 women will be diagnosed with breast cancer in the U.S. in 2006, though thanks to new options for patients, about 20 percent, or 40,000 patients will die. Even with improved therapies, the chance of a woman having breast cancer at some time in her life is still about one in eight.