"While large scale clinical studies have not yet been completed to confirm the prevalence of C35 in breast cancer patients, we are excited about these results and hope that C35 may eventually become a target of therapy and predictor of prognosis in breast cancer," said Deepak M. Sahasrabudhe, M.D., director of the Hematology-Oncology Fellowship Program and Professor of Medicine and Oncology at the University of Rochester School of Medicine and Dentistry, New York.
The study, a collaboration between the University of Rochester and Vaccinex, Inc., found that the C35 gene is located on chromosome 17 adjacent to the oncogene that encodes HER2/neu (human epidermal growth factor receptor 2). Development of therapy targeting HER2/neu has been a major advance for breast cancer patients.
The study showed that the protein encoded by the C35 gene was over-expressed in 65 percent of the breast cancers. Researchers compared it with HER2/neu, which is expressed in approximately 30 percent of breast cancers, and is associated with a more virulent form of breast cancer. In breast cancer, the grade of the tumor refers to the degree of malignancy or differentiation of tumor tissue, e.g., well, moderately well, or poorly differentiated, and undifferentiated or anaplastic. Prognosis of patients with higher grade (grades II/III) cancers is worse. In grade II/III tumors, 34 percent tested positive for both C35 and HER2/neu and 31 percent were positive for C35 and negative for HER2/neu. All cells that expressed HER2/neu also over-expressed C35. There were no cases that were positive for HER2/neu and negative for C35.
They found that C35 accumulates within the core of tumor cells. As the cells are killed, the C35 is released from the dying cell through internal membranes into surrounding tissue. Researchers are working to develop a diagnostic test to detect the presence of C35 protein or antibodies to that protein in a patient's blood and to develop potential treatments.
Researchers believe that traditional treatment methods alone will not be effective against C35 positive breast cancer, much in the same way that they are not effective against HER2/neu positive breast cancer. "We believe that future treatment of C35 positive breast cancer will be a two-pronged approach," said Dr. Sahasrabudhe. "It may entail an agent targeting C35, together with standard radio- or chemotherapy to induce further tumor cell death. A vaccine therapy to prevent the growth of C35-expressing tumor cells might also be a treatment approach."
Breast cancer is the second-leading cause of cancer-related death in women. According to the American Cancer Society, in 2003 more than 266,000 women and 1,300 men will be diagnosed with breast cancer and more than 39,000 women and 400 men will die from the disease.
Founded in 1907, the American Association for Cancer Research (AACR) is a professional society of more than 20,000 laboratory and clinical scientists engaged in cancer research in the United States and more than 60 other countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals (Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention). AACR's annual meeting attracts more than 12,000 participants who share new and significant discoveries in the cancer field, and the AACR's specialty meetings throughout the year focus on all the important areas of basic, translational and clinical cancer research.