1. Date of download: 7/7/2016 From: Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Systematic Evidence Review for the U.S. Preventive Services Task Force Ann Intern Med. 2005;143(5):362-379. doi:10.7326/0003-4819-143-5-200509060-00012 Analytic framework.KQBRCABRCABRCABRCA1BRCA2Key question ( ) 1: Do risk assessment and mutation testing lead to a reduction in the incidence of breast and ovarian cancer and cause-specific or all-cause mortality? KQ 2A: How well does risk assessment for cancer susceptibility by a clinician in a primary care setting select candidates for mutation testing? KQ 2B: What are the benefits of genetic counseling before testing? KQ 2C: Among women with family histories predicting an average, moderate, or high risk for a deleterious mutation, how well does mutation testing predict risk for breast and ovarian cancer? KQ 3: What are the adverse effects of risk assessment, genetic counseling, and testing? KQ 4: How well do interventions reduce the incidence and mortality of breast and ovarian cancer in women identified as high risk by history, positive genetic test results, or both? KQ 5: What are the adverse effects of interventions? *Indicates clinically significant mutation of or. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

2. Date of download: 7/7/2016 From: Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Systematic Evidence Review for the U.S. Preventive Services Task Force Ann Intern Med. 2005;143(5):362-379. doi:10.7326/0003-4819-143-5-200509060-00012 Relative risks for breast cancer in chemoprevention trials.Error bars represent 95% CIs. IBIS = International Breast Cancer Intervention Study. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

3. Date of download: 7/7/2016 From: Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Systematic Evidence Review for the U.S. Preventive Services Task Force Ann Intern Med. 2005;143(5):362-379. doi:10.7326/0003-4819-143-5-200509060-00012 Yield of testing forBRCAmutations in a hypothetical population based on assumptions in Table 6.NNS = number needed to screen. *Based on estimates for mastectomy. †Based on estimates for oophorectomy. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

4. Date of download: 7/7/2016 From: Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Systematic Evidence Review for the U.S. Preventive Services Task Force Ann Intern Med. 2005;143(5):362-379. doi:10.7326/0003-4819-143-5-200509060-00012 Yield of literature search and review.ELSI = ethical, legal, and social implications. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians