Genetics and Cancer Care Cynthia Forster-Gibson, MD, PhD and Loren - - PowerPoint PPT Presentation

Genetics and Cancer Care

Cynthia Forster-Gibson, MD, PhD and Loren Mackay- Loder, MSc – Genetics Program, THP

Faculty/Presenter Disclosure

Faculty: Cynthia Forster-Gibson Relationships with commercial interests: None Presenter: Loren Mackay-Loder Relationships with commercial interests: None

Cancer distribution

Sporadic; 70% Single gene cause known, 10% no known gene(s), 20% Familial; 30%

How do you identify those appropriate for referral to Genetics

 Personal history

• age(s) at cancer diagnosis
• tumour pathology
• bilaterality
• synchronous tumours
• gender
• ther organ involvement (eg. ovary, stomach, skin)

How do you identify those appropriate for referral to Genetics

• Family history
• tumour type, age at diagnosis, bilateral,

synchronous, gender

• maternal and paternal relatives
• full and half relationships
• affected and unaffected individuals
• ethnicity (founder mutations)
• any limitations with the family history

Information to include with the referral

• If patient is affected
• Tumour pathology
• If patient is unaffected
• Details of family history (including relationship to

patient, age at cancer diagnosis, cancer pathology if known

• If referral is based on pathogenic variant in

the family

• Copy of family members genetic test result

The genetic assessment

• Family history reviewed
• Confirm pathology
• Determine if/what testing is appropriate
• Identify best testable person
• Review pros and cons of testing
• Management options (broadly)

Genetic testing

• Testing approaches
• Single genes
• Multigene panels
• Results
• Pathogenic
• Likely pathogenic
• Variant of uncertain significance -Periodic review
• Benign variants
• No variant – uninformative – not negative- Family history

remains important

• Reclassification

New complexities of genetic testing

• Panel testing
• Increased chance of one or more VUS
• Positive test result that doesn’t match the personal
• r family history
• Some genes of limited value/information

Resources

• THP Clinical Genetics website
• http://trilliumhealthpartners.ca/patientservices/geneti

cs/Pages/default.aspx

• Referral form
• https://trilliumhealthpartners.ca/patientservices/gene

tics/Documents/3991_DHR_Familial_Cancer_Genet ics_Referral_Form_Fillable.pdf

What to discuss with your patient?

• Genetic factors are risk factors
• Clue to their presence may be personal

and/or family history

Sporadic vs Hereditary Cancer

http://www.web- books.com/eLibrary/Medicine/Cancer/04MB9.html H ttp://www.web-books.com/eLibrary/Medicine/Cancer/04MB9.html H http://www.web-books.com/eLibrary/Medicine/Cancer/04MB9.html

What to discuss with your patient?

• Knowledge of your genetic status may:
• Give you a better estimate of your specific

cancer risks

• Determine if you need a specialized screening

program for early detection

• Allow you to take measures (prophylactic

surgery, chemoprevention) to reduce your risk

• Heighten (your) primary care provider’s

awareness of your specific cancer risks

• Help you understand your children’s (and other

family members’) risks

What to discuss with your patient?

• Genetic factors are universal risk factors
• Regardless of ethnic background, cultural

practices

• They may inherited or new
• Your patient did not do anything to make this

happen

• They are there from conception to death
• If you know about them, you may be able to

decrease your risk of cancer or find it early

http://www.cancer.gov/about-cancer/causes-prevention/genetics/overview-pdq

How does ethnic variation influence testing or test interpretation?

• Specific pathogenic variants exist in specific

ethnic groups

• BRCA1 and BRCA2 – 3 specific pathogenic variants

in individuals of Ashkenazi Jewish descent

• specific variants in Icelanders, French Canadians,

Portugese etc

• Our knowledge of rare variants in some ethnic

groups is limited

• Our knowledge of cancer risk genes in some

groups is limited (Filipinos, Jamaicans etc) – not studied well, ethnic diversity

What to discuss with your patient?

• Barriers
• Evidence for reduced provincial cancer

screening in some immigrant populations

• Reasons are complex, include cultural,

physician, financial factors

• Language – need for a translator
• Type of cancer

Factors that should influence management choices/discussions

• High risk gene?
• BRCA1, BRCA2
• PTEN, STK11, CDH1, PALB2, TP53
• Lynch-associated – MSH2, MSH6, MLH1, PMS2, EPCAM
• Moderate risk gene?
• CHEK2 – particularly with positive family history, ATM, NBN
• Cancer risk not necessarily clear
• Family History

How to support your healthy (“unaffected”) high risk patient

• Genetic factors are lifelong risk factors
• Decision-making will be different at different

life stages

• Management will change over time and

should be reviewed periodically

• NCCN

https://www.nccn.org/professionals/physicia n_gls/default.aspx

How to support your high risk patient with cancer

• Genetic factors may alter the treatment plan

(eg. PARP inhibitors in women with ovarian cancer who have a BRCA2 pathogenic variant)

• There may be risks for other cancer types
• Decision-making will be different depending on

their health status

• Management will change over time and should

be reviewed periodically

• NCCN

https://www.nccn.org/professionals/physician_ gls/default.aspx

Thanks!

Questions?