BRCA testing in women with ovarian cancer Dr Carole Brewer Peninsula Clinical Genetics Service 15 January 2016 Consultant clinics Genetic nurse or counsellor clinics Peninsula Clinical Genetics Service Genetic mutations Genes that control cell growth- tumour suppressors, oncogenes etc. Germline mutations (vs somatic) Diagnostic- mutation searching Predictive- testing for known family mutation Referrals- tend to be unaffected people Referrals to PCGS Reasons for BRCA testing For the benefit of family: Predictive tests for relatives Management of future risks- patient and relatives Reasons for BRCA testing For the benefit of family: Predictive tests for relatives Management of future risks- patient and relatives Influence current management Ovca 63 brca 47 brca 35 Ovca 63 brca 47 brca 35 BRCA1 mutation Ovca 63 brca 47 brca 35 Predictive genetic testing Unaffected, at-risk relatives Usually at 50% risk Mutation already identified in family Usually 2 counselling appointments, 4 weeks apart, blood taken at second Result 4 weeks later, given in person. Ovca 63 brca 47 brca 35 Mutation positive Mutation negative BRCA mutation carriers Ovarian cancer risks determined by Gene Family history BRCA1: 20-60% BRCA2: 10-20% Age-related ovca risks BRCA1- less than 2% before 40, From 45, 1% per annum, rising to 2.5% at 65y BRCA2 Later and lower 60 8.2% with no, or unknown FH Australian ovarian cancer study group Alsop et al J clin oncol 2012 n=1001: non-mucinous, unselected for FH, any age Overall pick up 14% (n=141, with 83 VUS) 16.6% serous 22.6% High Grage Serous 8.3% >60 8.2% with no, or unknown FH Australian ovarian cancer study group Alsop et al J clin oncol 2012 n=1001: non-mucinous, unselected for FH, any age Overall pick up 14% (n=141, with 83 VUS) 16.6% serous 22.6% HGS 8.3% >60 8.2% with no, or unknown FH Australian ovarian cancer study group Alsop et al J clin oncol 2012 n=1001: non-mucinous, unselected for FH, any age Overall pick up 14% (n=141, with 83 VUS-8.2% 16.6% serous 22.6% HGS 8.3% >60 8.2% with no, or unknown FH Typical BRCA patient Ovarian cancer Serous FIGO 3 Grade 3 Young (55 v 60.5) No PH brca, but often FH but, compared with overall cohort Fallopian tube and PPC FIGO 3 and 4 Age: PH: 27% brca (8% cohort overall) FH: 53% (19% cohort overall) BRCA mutations in unselected ovarian cancer Greek cohort- 6 founder mutations BRCA1 mutations in 27/592 (4.6%) sporadic cases 71% cases with mutation were HGS Stavropoulou et al 2013 Peninsula experience: BRCA testing in HGS ovca