Download Free Medical BRCA testing in women with ovarian cancer PowerPoint Presentation

BRCA testing in women with ovarian cancer PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical presentation on Familial Pancreatic Cancer, which is titled "BRCA testing in women with ovarian cancer", to know about BRCA testing and its benefits in managing the future risks-patient and relatives.

Tags : Familial Pancreatic Cancer, BRCA testing, women, ovarian cancer

Published on : May 18, 2021 | Views : 2448 | Downloads : 0

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

BRCA testing in women with ovarian cancer Dr Carole Brewer Peninsula Clinical Genetics Service
Slide 2-

Consultant clinics Genetic nurse or counsellor clinics Peninsula Clinical Genetics Service www.peninsulaclinicalgeneticsservice.co.uk/
Slide 3-

ppt slide no 3 content not found
Slide 4-

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
Slide 5-

Referrals to PCGS
Slide 6-

Reasons for BRCA testing For the benefit of family: Predictive tests for relatives Management of future risks- patient and relatives
Slide 7-

Reasons for BRCA testing For the benefit of family: Predictive tests for relatives Management of future risks- patient and relatives Influence current management
Slide 8-

Ovca 63 brca 47 brca 35
Slide 9-

Ovca 63 brca 47 brca 35 BRCA1 mutation
Slide 10-

Ovca 63 brca 47 brca 35
Slide 11-

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.
Slide 12-

Ovca 63 brca 47 brca 35 Mutation positive Mutation negative
Slide 13-

BRCA mutation carriers Ovarian cancer risks determined by Gene Family history BRCA1: 20-60% BRCA2: 10-20%
Slide 14-

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 <1% per annum
Slide 15-

Age-related ovca risks BRCA1- low before 40, ~1% pa 40-60 0.6% by 40y 23% by 50y 30% by 60y 63% by 70y BRCA2-low before 50 0.4% by 50y 7.4% by 60y 27% by 70y
Slide 16-

Age-related ovca risks, (compared with breast cancer risks) BRCA1-breast cancer risk ~2% per annum 30’s onwards 0.6% by 40y (18%) 23% by 50y (49%) 30% by 60y (64%) 63% by 70y (70-80%) BRCA2- 0.4% by 50y (28%) 7.4% by 60y 27% by 70y (80%)
Slide 17-

Ovarian cancer Ovca 54
Slide 18-

Familial Ovarian cancer How to assess risk of ovarian ca?
Slide 19-

ppt slide no 19 content not found
Slide 20-

ppt slide no 20 content not found
Slide 21-

47y 38y 63y Breast cancer Ovarian cancer 37y 42y 54y Gill Jo Marjorie, 70y Pat Shirley Rose Ivy 42y 63y
Slide 22-

Ovca 63 brca 47
Slide 23-

Manchester scoring system (Evans et al , 2004)
Slide 24-

Manchester scoring system (Evans et al , 2004)
Slide 25-

Manchester scoring system-revised, taking into account histology (Evans et al )
Slide 26-

Manchester scoring system-revised, taking into account histology (Evans et al )
Slide 27-

Score 15 =10% chance of finding a mutation Score of 20=20% chance Manchester scoring system
Slide 28-

Genetic factors BRCA1/2 Other highly penetrant genes? Environmental factors Moderate family history, modest increased risk Genetic testing or surgery not usually indicated
Slide 29-

Other potential ovarian cancer susceptilibity genes: RAD51B, RAD51C, RAD51D 28/3429 (0.82%) cases v 3/2000 controls (0.11%) Odds ratios 5.2 – 12 depending on gene =moderate risk, but rare Song et al 2015
Slide 30-

Other potential ovarian cancer susceptilibity genes:BRIP1, BARD1,PALB2, NBN BRIP: 0.9% cases, 0.09% controls. RR 11 EOC, 14 for HGS ovca BARD1, PALB2, NBN: No difference between cases and controls Ramus et al 2015
Slide 31-

47y 38y 63y Breast cancer Ovarian cancer 37y 42y 54y Gill Jo Marjorie, 70y Pat Shirley Rose Ivy 42y 63y
Slide 32-

47y 38y 63y Breast cancer Ovarian cancer 37y 42y 54y Gill Jo Marjorie, 70y Pat Shirley Rose Ivy 42y 63y Manchester score: 57!
Slide 33-

47y 38y 63y 37y 42y 54y Gill Jo Marjorie, 70y Pat Shirley Rose Ivy 42y BRCA1 mutation
Slide 34-

Ovca 63 Manchester sore: 10+6 =16 brca 47
Slide 35-

Ovca 63 Manchester sore: 10+6 =16 ~10% chance of finding a mutation brca 47
Slide 36-

Ovca 63 No surviving affected relative brca 47
Slide 37-

Ovca 63 No surviving affected relative, So chance of mutation 5% (no testing) brca 47
Slide 38-

ppt slide no 38 content not found
Slide 39-

Ovarian cancer Ovca 54 Why is important to know?
Slide 40-

Double stranded DNA Normal cell
Slide 41-

Double stranded DNA DS-DNA break Normal cell
Slide 42-

Repaired by Homologous repair system –HR (BRCA1, BRCA2, RAD51 etc) Error-free Double stranded DNA Normal cell
Slide 43-

Repaired by Homologous repair system –HR (BRCA1, BRCA2, RAD51 etc) Error-free Double stranded DNA Normal cell
Slide 44-

Repaired by Homologous repair system –HR (BRCA1, BRCA2, RAD51 etc) Error-free BRCA-deficient cell
Slide 45-

Repaired by Homologous repair system –HR (BRCA1, BRCA2, RAD51 etc) Error-free Repaired by non-HR system PARP -dependent Error prone BRCA-deficient cell
Slide 46-

Repaired by Homologous repair system –HR (BRCA1, BRCA2, RAD51 etc) Error-free Repaired by non-HR system PARP -dependent Error prone BRCA-deficient cell
Slide 47-

Repaired by Homologous repair system –HR (BRCA1, BRCA2, RAD51 etc) Error-free Repaired by non-HR system PARP -dependent Error prone BRCA-deficient cell
Slide 48-

Repaired by Homologous repair system –HR (BRCA1, BRCA2, RAD51 etc) Error-free Repaired by non-HR system PARP -dependent Error prone BRCA-deficient cell
Slide 49-

Repaired by Homologous repair system –HR (BRCA1, BRCA2, RAD51 etc) Error-free BRCA-deficient cell Repaired by non-HR system PARP -dependent Error prone
Slide 50-

Repaired by Homologous repair system –HR (BRCA1, BRCA2, RAD51 etc) Error-free BRCA-deficient cell Repaired by non-HR system PARP -dependent Error prone
Slide 51-

Repaired by Homologous repair system –HR (BRCA1, BRCA2, RAD51 etc) Error-free BRCA-deficient cell With PARP inhibition
Slide 52-

Repaired by Homologous repair system –HR (BRCA1, BRCA2, RAD51 etc) Error-free BRCA-deficient cell With PARP inhibition
Slide 53-

Repaired by Homologous repair system –HR (BRCA1, BRCA2, RAD51 etc) Error-free BRCA-deficient cell With PARP inhibition
Slide 54-

ppt slide no 54 content not found
Slide 55-

Management of BRCA-related ovarian cancer Better prognosis Respond to platinum and non-platinum (even if early relapse) Olaparib treatment/ PARPi trials limiting testing may be denying some patients a useful therapeutic option?
Slide 56-

Why not test everyone?
Slide 57-

Why not test everyone? Cost Genetic testing Counselling
Slide 58-

Why not test everyone? Cost Genetic testing #500+ Counselling
Slide 59-

Why not test everyone? Cost Genetic testing Counselling Interpretation of results (Cancer penetrance)
Slide 60-

Why not test everyone? Cost Genetic testing Counselling Interpretation of results (Cancer penetrance) Variants of uncertain significance (VUSs)
Slide 61-

Variants of uncertain significance (VUSs) Sequence change in gene that isn’t clearly pathogenic
Slide 62-

Variants of uncertain significance (VUSs) Sequence change in gene that isn’t clearly pathogenic How common?
Slide 63-

Variants of uncertain significance (VUSs) Sequence change in gene that isn’t clearly pathogenic How common?- 5-10%
Slide 64-

Ovarian cancer Ovca 54 Chance of VUS =chance of pathogenec mutation
Slide 65-

Ovarian cancer Ovca 54 BRCA2 VUS ?
Slide 66-

Variants of uncertain significance (VUSs) Sequence change in gene that isn’t clearly pathogenic How common?- 5-10% Can we use these for predictive testing?
Slide 67-

Variants of uncertain significance (VUSs) Sequence change in gene that isn’t clearly pathogenic How common?- 5-10% Can we use these for predictive testing?- NO!
Slide 68-

Variants of uncertain significance (VUSs) Sequence change in gene that isn’t clearly pathogenic How common?- 5-10% Can we use these for predictive testing?- NO! Will these be resolved in foreseeable future?
Slide 69-

Variants of uncertain significance (VUSs) Sequence change in gene that isn’t clearly pathogenic How common?- 5-10% Can we use these for predictive testing?- NO! Will these be resolved in foreseeable future? Unlikely
Slide 70-

Ovarian cancer Will she benefit from PARPi?
Slide 71-

Variants of uncertain significance (VUSs) Sequence change in gene that isn’t clearly pathogenic How common?- 5-10% Can we use these for predictive testing?- NO! Will these be resolved in foreseeable future? Unlikely Will this woman benefit from PARPi?
Slide 72-

Ovarian cancer Ovca 54 How likely is a BRCA mutation? Is there any family history?
Slide 73-

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
Slide 74-

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
Slide 75-

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
Slide 76-

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
Slide 77-

Typical BRCA patient Ovarian cancer Serous FIGO 3 Grade 3 Young (55 v 60.5) No PH brca, but often FH
Slide 78-

…but, compared with overall cohort Fallopian tube and PPC FIGO 3 and 4 Age: 41-50 PH: 27% brca (8% cohort overall) FH: 53% (19% cohort overall)
Slide 79-

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
Slide 80-

Peninsula experience: BRCA testing in HGS ovca <60 40 referrals since Sept 2013 24 offered testing 2 declined 4 results awaited 12 negative 4 positive 2* Variant of uncertain significance (VUS)
Slide 81-

BRCA testing in HGS ovca <60 of the 18 results
Slide 82-

BRCA testing in HGS ovca <60 of the 17 results 4 (23.5%) positive
Slide 83-

BRCA testing in HGS ovca <60 of the 18 results 3 (17.6%) positive 12 (67%) negative
Slide 84-

BRCA testing in HGS ovca <60 of the 18 results 3 (17.6%) positive 12 (70%) negative 2 (11%) uncertain
Slide 85-

29317 HGS Ovca 42y Cancer (nos) 40 ‘Endometrial’ ca 70 72 68 63 85 82 ‘womb’ 1901 54
Slide 86-

HGS Ovca 46y Died young 72 Multiple myeloma 60 78 No cancers 86 No info Embolism 78 25691 G2 IDC 46 ?brca 60s BRCA neg
Slide 87-

28019 PPC 50y ‘spine’ cancer 79y Lung 70 82y ?breast cancer
Slide 88-

31889 PPC 65y 71 heart
Slide 89-

BRCA testing threshold 10% chance of a pathogenic mutation Manchester Score 15, eg 2 ovca any age 1 ovca <60 plus brca any age 1 ovca >60 age, plus 2 brca <60, High grade serous ovca <60y (MS13)
Slide 90-

Genetic testing: BRCA1/2 searching for a mutation Manchester scoring system used to select families for testing. Threshold 10% chance of mutation Blood from affected relative 8 weeks
Slide 91-

Consider Should we be testing more women with ovarian cancer? Should we be testing all women with ovarian cancer? High grade serous- how many women? Refer to genetics? ways to incorporate this in to routine care pathway? Future involvement of clinical genetics?
Slide 92-

The future Continue to refer all women for BRCA testing to clinical genetics? If purpose is to determine management testing by oncology? Collaborative approach? Testing by oncol with input from CG
Slide 93-

Pros and cons: status quo pros Patient: Detailed FH assessment, and thorough genetic counselling Gynaeoncol: One less thing… Clinical genetics:maintains control, gatekeeping etc cons Patient and oncol: Waiting time/delays CG: Workload
Slide 94-

Pros and cons -full mainstreaming Pros Pt: seamless, (fewer delays) GO: control GC: workload, successful maintreaming Cons PT:Family issues GO: FUNDING, one more thing… CG: loss of gatekeeping etc
Slide 95-

Pros and cons -collaborative approach Pros Best of both worlds Involvement in process, maintains control Successful collaboration- mainstreaming Cons None? Funding None (other than setting up) Cheaper overall
Slide 96-

Consultant clinics Genetic nurse or counsellor clinics Peninsula clinical genetics service www.peninsulaclinicalgeneticsservice.co.uk/
Slide 97-

ppt slide no 97 content not found