In what may be a significant advance for the treatment of breast cancer, researchers have discovered they can more effectively wipe out diseased tissue when standard chemotherapy is combined with a drug //that shuts down certain molecular pathways involved in causing cancer.

In a multicenter clinical trial reported in the Jully, 2006 issue of the Journal of Clinical Oncology, women with locally advanced breast cancer were given an oral medication that inhibits an enzyme called farnesyltransferase, in addition to routine chemotherapy, before undergoing surgery. Farnesyltransferase is required to set in motion a series of molecular events involved in the development of cancer.

Analysis of the breast tissue taken at surgery showed no signs of cancer in a third of the patients.

"The findings are extremely encouraging," said Dr. Joseph Sparano, lead author of the study and director of the Breast Evaluation Center at the Montefiore-Einstein Cancer Center. "Eradication of cancer cells in breast tissue is a short-term endpoint that translates into a greater chance of cure in the long term. This combination of therapies definitely looks promising, and we are moving ahead with larger trials to confirm our results.”

The study included 21 women with locally advanced breast cancer who were considered suboptimal candidates for surgery because of the advanced stage of their disease. They received standard chemotherapy, doxorubicin and cyclophosphamide, given intravenously once every two weeks for four treatments. After each chemotherapy treatment, they also received 200 mg of tipifarnib, which inhibits farnesyltransferase, twice a day for six days. All patients then underwent a mastectomy or a lumpectomy.

Pathological analyses of breast tissue retrieved from the surgeries showed no cancerous tissue in seven patients, or 33 percent of the women who received the treatment, compared with 5 to 10 percent expected with chemothe
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