Project 172175

Axillary lymph node status in breast cancer is the most important factor in predicting a patient's risk of recurrence of disease. Patients whose disease has not spread to the lymph nodes (axillary node-negative, ANN) generally have a good prognosis; however, 20-30% of ANN patients will experience disease recurrence. This limit in prognostic ability of lymph node status has led our team to a search for markers with prognostic power to aid in determining which ANN patients may benefit from therapy. We recruited women with ANN breast cancer from eight Toronto hospitals to participate in the study. We obtained biospecimens and clinical follow-up information from the group. We have found that certain genetic changes in the tumor, such as increased number of copies of the HER2 gene, can predict those patients most likely to have a recurrence. We also found that the presence of lymphatic invasion is predictive of recurrence. We have identified novel patterns of genes that distinguish tumors with and without lymphatic invasion and related to recurrence. We will continue to investigate the alterations in breast tumors. We will evaluate how the patterns can be used to predict recurrence. We will study the genes to discover how changes in the genes can be involved in breast cancer. Our studies may lead to the identification of novel genes involved in breast cancer. By studying tumors from a large number of women with ANN breast cancer we will be able to determine the clinical importance of the genetic changes. The protein products of some of these genes may be targets for the development of new cancer treatments, as Herceptin has been for tumors that overexpress HER2. Our goals are to explore the clinical importance of these genes to diagnose women early enough to prevent or diminish the effects of breast cancer, to tailor treatment to increase the likelihood of a cure, and to identify novel targets for new cancer therapeutics.