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Mutation Testing and Breast Ovarian Cancer PowerPoint Presentation

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  • Slide 1 - BRCA1/2 Mutation Testing and Breast/Ovarian Cancer in the Ashkenazi Jewish Population Glenn E Palomaki, B.S. Foundation for Blood Research Scarborough, Maine (207) 883-4131 palomaki@fbr.org
  • Slide 2 - p (1,000,000) Cumulative incidence (N) = cs (cf) CF = Carrier Frequency (carrier rate as a percentage) CS = Clinical sensitivity (%) P = Penetrance (%) Use consensus estimates/ranges for each variable. Integrated Approach
  • Slide 3 - Carrier Rate The rate of three founder BRCA1/2 mutation carriers among the Ashkenazi Jewish population 6174delT (BRCA2) All three combined 5382insC (BRCA1) 185delAG (BRCA1) 1 in 66 to 1 in 111 1 in 33 to 1 in 56 1 in 250 to 1 in 833 1 in 92 to 1 in 130 Fodor et al., 1998; Hartge et al., 1999; Oddoux et al., 1996; Roa et al., 1996; Struewing et al., 1995; Struewing et al., 1997.
  • Slide 4 - Clinical Sensitivity Proportion of Ashkenazi Jewish women with breast cancer at any age carrying a BRCA1/2 mutation Fodor et al., 1998; Hartge et al., 1999; Oddoux et al., 1996; Roa et al., 1996; Struewing et al., 1995; Struewing et al., 1997.
  • Slide 5 - Penetrance Proportion of Ashkenazi Jewish women with a founder mutation that develops cancer by age 70 30 to 70% BRCA1 & BRCA2 (weighted average) 26 to 74% BRCA2 alone 36 to 69% BRCA1 alone Warner et al., 1999; Satagopan et al., 2001; King et al., 2003; Fodor et al., 1998; Struewing et al., 1997; Moslehi et al, 2000.
  • Slide 6 - Cumulative Incidence Proportion of Ashkenazi Jewish women that will develop breast cancer by age 70 DevCan Software: Probability of developing or dying of cancer. Version 5.1: Statistical Research and Application Branch, National Cancer Institute; 2003. Ashkenazi Jewish women similar?
  • Slide 7 - Cumulative Incidence of Breast Cancer by Age 70 (Among Ashkenazi Jewish women using a carrier rate of 1 in 40) 12 11 10 9 8 7 Penetrance (%) 70 60 50 40 30 Yellow indicates combinations with cumulative incidences within 10% of the overall rate for Caucasians 146,000 159,000 175,000 194,000 219,000 250,000 125,000 136,000 150,000 167,000 188,000 214,000 104,000 114,000 125,000 139,000 156,000 179,000 83,000 91,000 100,000 111,000 125,000 143,000 62,000 68,000 75,000 83,000 94,000 107,000 Clinical Sensitivity (%)
  • Slide 8 - Breast and Ovarian Cancer Risks due to Inherited Mutations in BRCA1 and BRCA2 (Mary-Claire King et al., Science, Oct 2003) Studied a cohort of 1,008 Ashkenazi women with breast cancer (index cases), regardless of family history Family members of those carrying a mutation were genotyped and cancer history collected Reported that half of all mutation carriers had no family history clinical sensitivity is 10.3% 2.5% of Ashkenazi Jewish women carry a mutation the BRCA1/2 penetrance to age 70 is 71%
  • Slide 9 - 1,000,000 followed age 20 to age 70 25,000 (2.5%) have a BRCA1/2 mutation 975,000 do not have a BRCA1/2 mutation 159,750 develop cancer 815,240 do not develop cancer 71% develop cancer (17,750) 7,250 do not develop cancer Evaluate Finding Using the Integrated Approach Cumulative Incidence is 177,500 - 80% higher than the rate expected in Caucasians
  • Slide 10 - Comparison of Three Studies of Breast Cancer in Ashkenazi Jewish Women Component King Warner Satagopan Clin Sensitivity 10.3% 11.6% 10.1% Penetrance (by 70) 71% 50% 40% Carrier Rate -- assumed to be 1:40 -- Cumulative Incidence* 178,000 104,000 100,000 * Computed cumulative incidence per million women by age 70. In Caucasian women, the SEER rate is 96,000.
  • Slide 11 - Acknowledgments Work was supported by a cooperative agreement with the CDC, Office of Genomics and Disease Prevention (CCU319352) Background information collected as part of an ACCE Review: Breast/Ovarian Cancer and BRCA1/2 Mutations (available on the CDC website)
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