1 / 23

BRCA1 and BRCA2 Mutations and Breast Cancer:

BRCA1 and BRCA2 Mutations and Breast Cancer:. An Integrated Approach Using Four Epidemiologic Parameters. Monica McClain, PhD. Assistant Director, Biometry and Epidemiology Foundation for Blood Research Scarborough, Maine  Email: mcclain@fbr.org.

Antony
Download Presentation

BRCA1 and BRCA2 Mutations and Breast Cancer:

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. BRCA1 and BRCA2 Mutations and Breast Cancer: An Integrated Approach Using Four Epidemiologic Parameters Monica McClain, PhD.Assistant Director, Biometry and Epidemiology Foundation for Blood Research Scarborough, Maine  Email: mcclain@fbr.org

  2. Epidemiologic Parameters

  3. Cumulative Incidence Proportion of women that will develop breast cancer by a given age DevCan: Probability of developing or dying of cancer software. Version 5.1: Statistical Research and Application Branch, National Cancer Institute; 2003.

  4. Clinical Sensitivity Proportion of women with breast cancer by a given age carrying a BRCA1/2 mutation

  5. Penetrance Proportion of women with a BRCA1/2 mutation that develops breast cancer by a given age Anglian Breast Cancer Study Group. Br J Cancer. 2000; Easton et al. Am J Hum Genet. 1995; Antoniou et al. Am J Hum Genet. 2003; Antoniou et al. Br J Cancer. 2002; Antoniou et al. Genet Epidemiol. 2000; Brose et al. J Natl Cancer Inst. 2002; Ford et al. Am J Hum Genet. 1998; Schubert et al. Am J Hum Genet. 1997.

  6. Carrier Rate The rate of BRCA1/2 mutation carriers in the general population Anglian Breast Cancer Study Group. Br J Cancer. 2000; Antoniou et al. Br J Cancer. 2002; Antoniou et al. Genet Epidemiol. 2000; Ford et al. Am J Hum Genet. 1995; Peto et al. J Natl Cancer Inst. 1999; Whittemore et al. Am J Hum Genet. Mar 1997.

  7. Meta-analysis for each parameter to calculate a point estimate but • Heterogeneity • Wide ranges, broad confidence intervals • Not internally consistent

  8. Integrated Approach 1 CR = (( CI * CS ) / P ) / 1,000,000 CR= Carrier Rate (1 in N) CI = Cumulative incidence (N out of 1,000,000) CS = Clinical sensitivity (%) P = Penetrance (%)

  9. Integrated Approach: C l i n i c a l S e n s i t i v i t y Results By Age 70 (assuming a cumulative incidence of 9.67%) Yellow indicates plausible combinations

  10. Applying the integrated approach to a hypothetical cohort of 1,000,000 women 1,000,000 followed from age 20 to age 70 96,700 will develop breast cancer 1,000,000 * 9.67 % Apply Cumulative Incidence of 9.67 %

  11. Con’t 1,000,000 followed age 20 to age 70 96,700 will develop breast cancer 903,300 will not develop breast cancer 1,000,000 - 96,700 Calculate those that will not develop breast cancer

  12. Con’t 1,000,000 followed age 20 to age 70 96,700 will develop breast cancer 903,300 will not develop breast cancer 1,450 BRCA1/2+ 96,700 1.5 % * Apply clinical sensitivity of 1.5 %

  13. Con’t 1,000,000 followed age 20 to age 70 96,700 will develop breast cancer 903,300 will not develop breast cancer 1,450 BRCA1/2+ 95,250 BRCA1/2 - 96,700 1,450 - Calculate non-BRCA1/2 mutation carriers in women with breast cancer

  14. Con’t 1,000,000 followed age 20 to age 70 96,700 will develop breast cancer 903,300 will not develop breast cancer 1,450 BRCA1/2+ 95,250 BRCA1/2 - 1,186 BRCA1/2 + (1,450 / 0.55) – 1,450 Calculate BRCA1/2 mutation carriers in women without breast cancer (penetrance = 55%)

  15. Con’t 1,000,000 followed age 20 to age 70 96,700 will develop breast cancer 903,300 will not develop breast cancer 1,450 BRCA1/2+ 95,250 BRCA1/2 - 1,186 BRCA1/2 + 902,114 BRCA1/2 - Calculate non-BRCA1/2 mutation carriers in women without breast cancer

  16. Con’t 1,000,000 followed age 20 to age 70 96,700 will develop breast cancer 903,300 will not develop breast cancer 1,450 BRCA1/2+ 95,250 BRCA1/2 - 1,186 BRCA1/2 + 902,114 BRCA1/2 - Carrier Rate: 2,636 / 1,000,000 or 1 in 380

  17. A Comparison Among Commonly Used Information Sources www.myriad.com www.ama-assn.org www.cancer.gov/cancerinfo/pdq www.genetests.org

  18. Calculated parameters using our integrated approach Each epidemiologic parameter is calculated by setting the other three parameters listed by the same information source as constants in our integrated approach

  19. What’s next? Expand the approach to incorporate family history

  20. Epidemiologic parameters needed when family history is used as a screening test Lancet. Oct 27 2001 Pharoah et al. Int J Cancer. 1997 * value fixed by the first three variables ** risk ratio computed using the other 6 variables

  21. Relationship Between Strong Family History, Breast Cancer and BRCA1/2 Mutation Status 1,000,000 Women followed from age 20 to 70 Strong Family History 10,000 Positive 990,000 Negative Develops Breast Cancer 3000 Yes 7000 No 93,700 Yes 896,300 No BRCA1/2 Mutation Present 2100 No 900 Yes 300 Yes 6700 No 550 Yes 93,150 No 750 Yes 895,550 No

  22. What’s next? • Expanded approaches • Family history • Ovarian cancer • Breast and ovarian cancer • Race/ethnicity (Ashkenazi Jewish) • Mutation location (BRCA1, BRCA2, OCCR) • Other conditions with a genetic component

  23. AcknowledgmentSupport for this study was provided by a cooperative agreement (UR/CCU319352) with the Centers for Disease Control and Prevention, Office of Genomics and Disease Prevention.

More Related