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

• other 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 or 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_Genetics_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-

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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/physician_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?