Genomic Medicine: Genomic Medicine -- An Updated Primer.

Cathy, a 40-year-old mother of three, arrives in your office for her annual physical. She has purchased a commercial genomewide scan (see the Glossary), which she believes measures the clinically meaningful risk that common diseases will develop, and has completed her family history online using My Family Health Portrait (www.familyhistory.hhs.gov), a tool developed for this purpose by the U.S. Surgeon General. Her genomewide scan suggests a slightly elevated risk of breast cancer, but you correctly recognize that this information is of unproven value in routine clinical care. On importing Cathy's family-history file, your office's electronic health record system alerts you to the fact that Cathy is of Ashkenazi Jewish heritage and has several relatives with breast cancer, putting her at heightened risk for the hereditary breast and ovarian cancer syndrome. The system prompts you to discuss Cathy's risk of breast and ovarian cancer during the visit. Considering both her family history and ancestry, you refer Cathy to a health care professional with advanced genetics training for consultation. In the coming months Cathy elects to have her DNA tested for mutations in BRCA1 and BRCA2, the genes associated with hereditary breast and ovarian cancer syndrome, and to undergo a mammographic examination. Although the results of her genetic tests are negative, her mammogram reveals a suspicious abnormality. A biopsy is performed, and breast cancer is detected. Surgery is successful. Pathological examination of tissue from the excised tumor reveals that it is positive for estrogen-receptor protein and negative for human epidermal growth factor receptor type 2 (HER2); the lymph glands are free of cancer cells. Genetic-expression profiling of the tumor indicates a relatively high risk of recurrent cancer, and Cathy elects to receive adjuvant chemotherapy followed by treatment with tamoxifen. Five years later, the cancer has not recurred. Copyright © 2010 Massachusetts Medical Society.