Dr Katie Snape Joint Lead Consultant for Cancer Genetics South West Thames Regional Genetics Service St Georges University Hospitals NHS Foundation Trust Approval ID GB17285 Date of Preparation June 2019 ID: 931529
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Slide1
Genetic testing in ovarian cancer
Dr Katie SnapeJoint Lead Consultant for Cancer Genetics,South West Thames Regional Genetics ServiceSt George’s University Hospitals NHS Foundation Trust
Approval ID: GB-17285
Date of Preparation: June 2019
Slide2Clinical information
Pathological information
Somatic (tumour) genomic dataFamily history assessment
Germline genomic data
Ovarian cancer patient
Current management
Management of future cancer risk
Management of relatives
Management at relapse
Slide3Germline/Constitutional
Somatic
Clinical management of current cancer/relapse
Management of future cancer risks and relative’s cancer risks
1. Neff R. T. et al. BRCA mutation in ovarian cancer: testing, implications and treatment considerations. Therapeutic Advances in Medical Oncology, 9(8), 519–531. (2017).
Slide4Case 1
39 year old presented with abdominal bloating and discomfort, lethargy and loss of appetiteDiagnosed with high grade serous ovarian cancerPaternal aunt with breast cancer aged 44
Ovarian cancer age 39
Breast cancer age 44
Slide5Ovarian cancer age 66
Case 2
66 year old presented with ascites
Diagnosed with high grade serous carcinoma of the ovary
No significant family history
Slide6Germline/Constitutional
Somatic
Clinical management of current cancer/relapse
Management of future cancer risks and relative’s cancer risks
1. Neff R. T. et al. BRCA mutation in ovarian cancer: testing, implications and treatment considerations. Therapeutic Advances in Medical Oncology, 9(8), 519–531. (2017).
Slide7Mutational signature/Circos
plot
Slide8Genetic testing results
Case 1: Germline BRCA1 mutationc. 5289delG
Case 2: Somatic BRCA2 mutationc.3103G>T_p.Glu1035*
Ovarian cancer age 39
Breast cancer age 44
Ovarian cancer age 66
Slide9Germline
BRCA1, BRCA2RAD51C, RAD51D, BRIP1, MMR genes
Somatic BRCA1, BRCA2
Clinical information
Pathological information
Somatic (tumour) genomic data
Family history assessment
Germline
genomic data
Ovarian cancer patient
Current management
Management of future cancer risk
Management of relatives
Management at relapse
Slide10Current management
1. Moore, K. et al Maintenance
Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N. Engl. J. Med. 379(26): 2495-2505 (2018).
Slide11Clinical information
Pathological information
Somatic (tumour) genomic data
Family history assessment
Germline
genomic data
Ovarian cancer patient
Current management
Management of future cancer risk
Management of relatives
Management at relapse
Slide12Case 1 – germline mutation
At personal risk of breast cancer – screening to commenceCascade screening of relatives Breast screeningRisk reducing removal of tubes and ovaries from age 40Reproductive options
Ovarian cancer age 39
Breast cancer age 44
1. Finch, A. et al. Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 32, 1547–1553 (2014); 2. Finch, A. et al.
Salpingo
-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 Mutation. JAMA 296, 185–192 (2006).
Slide13Diagnosis of ovarian cancer
Referral to surgeon/oncologist: acute management
Referral to clinical genetics
Family history and germline testing
BRCA +ve
PARP inhibitors at third line treatment
1
1. Ledermann, J. et al.
Olaparib
maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a
preplanned
retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 15, 852–861 (2014); 2. Moore, K. et al Maintenance
Olaparib
in Patients with Newly Diagnosed Advanced Ovarian Cancer. N. Engl. J. Med. 379 (26): 2495-2505 (2018).
Diagnosis of ovarian cancer
Referral to surgeon/oncologist: acute management,
FHx
and genetic testing: tumour testing and germline testing
Germline BRCA +
ve
Referral to clinical genetics: carrier management and cascade screening
BRCA +
ve
: PARP inhibitors at first line treatment
2
Slide14Opportunities and challenges
Opportunities
Widened and more equitable access to genetic testingBetter patient treatment outcomesIdentification of more genetically “at-risk” individuals; screening, prevention and early detectionChallenges“Mainstreamed testing”Resources (money and time)Education and training Novel clinical pathwaysAccess to testing
Consent and patient experience
Slide15Diagnosis of ovarian cancer
Referral to surgeon/oncologist: acute management,
FHx and PAIRED tumour testing and germline testingGermline BRCA +
ve
Referral to clinical genetics: carrier management and cascade screening
BRCA +
ve
: PARP inhibitors at first line treatment
2
Strategies
Online patient facing family history assessment
Education and training support
National Test Directory and Genomic Medicine Service
Standardised consent
Centralised online test requesting
Standardised reporting
“On call” genetic counsellor
Genomic Tumour Advisory Board
Clear referral pathways into inherited cancer services
1. Moore, K. et al Maintenance
Olaparib
in Patients with Newly Diagnosed Advanced Ovarian Cancer. N. Engl. J. Med. 379(26): 2495-2505 (2018).
Slide16Patient with ovarian cancer
Tumour BRCA panel analysis
Tumour biopsy/resectionDigitalised FHx
Management advice
Clinical genetics
Somatic MDT
Integrated molecular report
Pathology review
Tumour specific MDT for clinical management of current cancer/relapse
Management of future cancer risks and relative’s cancer risks
Germline BRCA +/-OC panel
Slide17Summary
Ovarian cancer patients may carrySomatic BRCA mutations (tumour only)Germline BRCA mutations (present in every cell)
Can only detect both by paired genetic testing of both tumour and bloodManagement of BRCA positive ovarian cancer is improved by PARP inhibition from first line therapyFurther identification of germline carriers enables management of future cancer risk and management of relativesChanges/innovation to our current pathways are required to implement the most clinically excellent, evidence-based and cost effective patient pathways
1.
Capoluongo
, E. et al Guidance Statement on BRCA1/2
Tumor
Testing in Ovarian Cancer Patients.
Semin
. Oncol. 44(3): 287-297 (2017).