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
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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?