ArticleRole of Biologic Markers in Patient Selection and Application to Disease PreventionDowsett, Mitch, Ph.D.; Ellis, Matthew J., M.B., Ph.D., F.R.C.P.Author Information From the Joint Institute of Cancer Research/Royal Marsden NHS Trust, Academic Department of Biochemistry, London, United Kingdom (M.D.) and Duke University Breast Cancer Program, Duke University Medical Center, Durham, North Carolina, U.S.A. (M.J.E.) 27710. Address correspondence and reprint requests to Dr. Mitch Dowsett, Academic Department of Biochemistry/Royal Marsden Hospital, London, United Kingdom SW3 6JJ. American Journal of Clinical Oncology: August 2003 - Volume 26 - Issue 4 - p S34-S39 Buy Abstract Aromatase inhibitors (AIs) are now under investigation for the treatment of early stage breast cancer and for disease prevention as alternatives to standard treatment with tamoxifen. Currently identified genetic risk factors of breast cancer include BRCA-1/BRCA-2 mutations, ATM mutations, and history of high estrogen levels, as evidenced by plasma analyses and/or dense bones. To date, estrogen receptor (ER) and progesterone receptor (PgR) status has predictive value for determining response to therapy in patients with hormone receptor-positive breast cancer (ER+ and/or PgR+ tumors). Recent studies have shown AIs to be safer and more effective than tamoxifen in postmenopausal women with advanced disease. Some data suggest that letrozole may be a more effective treatment than tamoxifen for patients with ER+ and/or PgR+ early breast cancers expressing ErbB-1 and/or ErbB-2. Changes in cell proliferation markers (e.g., S-phase fraction and Ki67 antigen), plasma lipid levels, and the bone resorption marker C-terminal peptide are biomarkers that have been evaluated for preventive and prognostic value in breast cancer patients and normal volunteers. Results from biomarker screens can be used to define inclusion criteria for clinical trials and eventually to individualize treatment. Gene expression profiling (microarray analysis), i.e., genomic and proteomic studies, will probably advance the discovery of new biomarkers for breast cancer prevention and treatment. © 2003 Lippincott Williams & Wilkins, Inc.