Cancer Genetics Louise Lynagh and Isabelle Danos Associate Genetic - - PowerPoint PPT Presentation

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Cancer Genetics Louise Lynagh and Isabelle Danos Associate Genetic - - PowerPoint PPT Presentation

Nov 11, 2022 394 likes •1.07k views

Cancer Genetics Louise Lynagh and Isabelle Danos Associate Genetic Counsellors Clinic ethos: cancer prevention and early detection SVH Cancer Genetics team Clinical Academic Professor Allan Spigelman 3 x Genetic Counsellors Louise

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Cancer Genetics

Louise Lynagh and Isabelle Danos Associate Genetic Counsellors

Clinic ethos: cancer prevention and early detection

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SVH Cancer Genetics team

  • Clinical Academic

– Professor Allan Spigelman

  • 3 x Genetic Counsellors

– Louise Lynagh – Isabelle Danos – Manisha Chauhan

  • Clinic Coordinator

– Sobia Dean

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10 18 44 60 61 72 88 112 95 77 112 129 133 203 198 400 465 545 100 200 300 400 500 600 98 99 00 01 02 03 04 05 06 07 08 09 10 11 12 13 14 15

New Referrals

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What is genetic counselling?

  • Genetic counselling is a communication process, which

aims to help individuals, couples and families understand and adapt to the medical, psychological, familial and reproductive implications of the genetic contribution to specific health conditions’

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Genetic services in NSW

State wide database Kintrak

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Process

  • 1. Construct family history (minimum 3 generation)
  • 2. Assess the likelihood of an inherited predisposition to cancer

– Types of cancer/ages at diagnosis – Confirm diagnoses: pathology, death certificate or verification through Cancer Institute (deceased 30yrs) – Ancestry – Consanguinity

  • 3. Coordinate genetic testing and gain informed consent
  • 4. Provide risk assessment based on PHx and FHx +/- GT results

– Offer surveillance recommendations for risk management

  • 5. Assess risk for relatives and link to cancer genetics
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Genetic testing

  • Targeted single gene tests:

– Mutation search

– Mutation found – No mutation found – VUS found

– Predictive testing

– Positive – Negative

– Founder mutation testing

– Positive – Negative

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Genetic Testing

  • Funding

– Cost of genetic testing billed to LHD of patient – Self funded testing

  • BRCA1/2 currently ≈$1200
  • Turnaround time

– 4-6 weeks, longer for rarer conditions – Urgent results within 14 working days

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Genetic Counselling

  • People often are interested in knowing…

…why did I develop cancer? …can I have a genetic test? …what might it mean for me and my family? …what are the pros and cons of genetic testing? …what can I do about my cancer risk? …what can my relatives do to manage their risk?

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Do I want to know?

  • Potential benefits
  • Tailor screening advice
  • Treatment related decisions
  • Sense of control
  • Alleviate anxiety
  • Remove uncertainty
  • More personalised risk assessment
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Do I want to know?

  • Potential harms
  • Anxiety/fear/depression
  • Guilt/blame
  • Bearer of bad news
  • Change to family relationships
  • Insurance issues
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Source: Stadler 2010 JCO 28(27):4255-4267.

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Breast cancer

  • Conditions

– Hereditary Breast Ovarian Cancer (BRCA1/2) – Li Fraumeni (tp53) – Cowden syndrome (PTEN) – Hereditary diffuse gastric cancer (CDH1) – Peutz-Jegher syndrome (STK11)

  • Risk assessment

– Manchester, BOADICEA

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boad

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Colorectal Cancer

  • Lynch Syndrome (MLH1, MSH2, MSH6, PMS2)
  • Familial adenomatous polyposis (APC)
  • MUTYH-associated polyposis (MUTYH)
  • Sessile serrated polyposis (?)
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Case 1

  • 31yo female with triple negative breast

cancer, undergoing neoadjuvant chemo before surgery

  • Referred by oncologist for a genetic review
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Txt focused genetic testing

  • Traditional GT done following cancer txt to

guide future risk management

  • TFGT done soon after cancer dx to guide initial

cancer txt

– Enabled by faster TAT – Inform surgical decisions (breast conservation vs therapeutic mastectomy +/- contralateral RR mastectomy) – Tailoring chemotherapy agents ie. PARP inhibitors and platinum based therapy

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Information preferences w/ TFGT

  • Timing

– Most women want to be informed about TFGT close to time of cancer dx, before decisions on cancer management – Some want to be informed at time of diagnosis, despite acknowledging that the time is fraught and emotionally overwhelming

  • Mode of delivery

– No clear preference for which healthcare professional should introduce TFGT (similar numbers for onc, surgeon, genetics professional or cancer care nurse) – But if presented by onc or surgeon, want to be able to discuss test result with genetics professional

  • Amount and format of information

– Face to face consultation plus additional written supporting info – Remain focused on the woman, briefly mention family implications

Meiser et al. (2012). Getting to the Point: What Women Newly Diagnosed With Breast Cancer Want to Know About Treatment-Focused Genetic Testing. Oncology Nursing Forum. Vol 39(2)

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Case 2

  • 37yo female
  • Referred by GP for genetic assessment
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“2 x VUS” 1 in BRCA1 1 in BRCA2

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“2 x VUS” 1 in BRCA1 1 in BRCA2 Polymorphism and likely benign VUS

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“2 x VUS” 1 in BRCA1 1 in BRCA2 Polymorphism and likely benign VUS Likely benign VUS BRCA2

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“2 x VUS” 1 in BRCA1 1 in BRCA2 Polymorphism and likely benign VUS Unaffected full BRCA1/2 sequencing and MLPA = no mutation identified. Variant classified as polymorphism

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BRCA1 deletion Unaffected full BRCA1/2 sequencing and MLPA = no mutation identified. Variant classified as polymorphism

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Case 3

  • 46yo female
  • Asked for GP referral following receipt of letter

from Australasian Colorectal Cancer Family Registry

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Case 4

  • 65yo female
  • Referred by GP for predictive BRCA1 testing.

Different BRCA1 mutations identified in sister and maternal cousin

  • HIV dx from blood transfusion 20yrs prior
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BRCA1 BRCA1

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BRCA1 BRCA1

Negative for both BRCA1 mutations

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Case 5

  • 36yo female with breast cancer
  • Referred by radiation oncologist given young

age and family history

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Case 6

  • SDHD
  • Succinate dehydrogenase complex subunit B
  • Found in inner mitochondrial membrane
  • Involved in citric acid cycle
  • Pts with mutation present with head and neck

paragangliomas/pheochromocytomas

  • Altitude can modify penetrance/avoid smoking
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SDHD: c.191_192delTC (p.Leu64ProfsX4)

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Case 7

  • 55yo male with CRC showing loss of staining

for MLH1 and PMS2 on IHC, and BRAF v600E negative

  • Referred by colorectal surgeon
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MLH1+

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Case 8

  • Lynch like
  • MMR IHC: loss of MLH1/PMS2
  • BRAF molecular – negative
  • Germline testing MLH1/PMS2 – no mutation

identified

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Case 9

  • 50yo male referred by oncologist for ?Birt-

Hogg-Dube assessment

  • PHx: renal cancer at 50, skin lesions

?fibrofolliculomas

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Case 10

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Case 11

  • 30yo female referred by GP for predictive

BRCA2 testing

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Case 12

  • Died CRC in 2004
  • Stored DNA on deceased family member
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MLH1+

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Case 13

  • IVF BRCA mutation
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Indicators for referral

  • Cancer at a young age
  • Bilateral or multifocal tumours
  • Multiple cancers in one patient or family
  • Ethnicity (founder mutations)
  • Tumour pathology

– Triple negative breast cancer – High grade serous ovarian cancer

  • Rare tumour types (Phaeochromocytoma,

paraganglioma, sarcoma, glioblastoma, choroid plexus carcinoma, retinoblastoma)