1. Genetic Counseling & Testing for Cancer Risk
Laura Colello, MS, CGC
Certified Genetic Counselor
Familial Cancer Program
University of Vermont Medical Center

2. Goals for this presentation
Who should consider genetic counseling for cancer risk?
What happens during an appointment for familial cancer risk assessment?
Overview of genetic testing for hereditary cancer syndromes

3. Why have genetic counseling for cancer?
Determine if someone is at increased risk for developing cancer based on their family history
Or, If a person has been previously diagnosed with cancer, do they have an increased risk of developing another cancer
Identify relatives who may be at increased risk for developing cancer
May change screening recommendations

4. Cancer Risk Assessment
Usually performed by a genetic counselor
Prior to your appointment, we like to gather information (we ask you to fill out a questionnaire prior to our visit):
Personal medical history
If you have had cancer: specific name of cancer, age at diagnosis, treatment?
Other medical history, including lifestyle, reproductive history, environmental exposures, cancer screening, and surgeries
Family history
For each family member (children, siblings, parents, aunts, uncles, grandparents, cousins)
If they had cancer, what type, age at diagnosis?
Current age or age they passed away

11. Who should consider calling the Familial Cancer Program?

12. Indications for cancer genetic counseling
People who have cancer diagnosed at a young age (generally < age 50)
People who have had multiple cancers or bilateral cancers
People who have had rare cancers (for example, male breast cancer)
Families with many people who have had cancer
Families that have had cancer that fits a pattern of a known hereditary cancer syndrome
For example, breast and ovarian cancer
For example, colon, uterine, and ovarian cancer

13. Looking for CLUES:

14. CLUE = AGE AT DIAGNOSIS Does the person have a personal or family
history of cancer
diagnosed at an earlier
age than that cancer
typically occurs?
(eg colon cancer under
age 50)

15. CLUE – pattern of cancers in person or family

16. Family Tree

17. Analysis of family tree allows us to
Determine a person’s personal risk for developing cancer, based on family history
Determine if genetic testing (of yourself or another family member) would help us clarify cancer risk in the family
Determine if people in the family should have screening for specific cancers

18. Sporadic

19. Family History

20. More suspicious family history
pedigree

21. CLUE = Pathology Reports
Polyps
Cancer
Dermatology

22. CLUE = Tumor Testing UVMMC: IHC testing UVMMC: Gene Panel Solid Tumor
FoundationOne

24. Deeper dive

25. Hereditary Cancer Genes
BRCA1 and BRCA2
Newer genes such as ATM, CHEK2, PALB2, BRIP1
Newer associations with prostate cancer and known cancer syndromes such as Lynch
Newer prostate cancer genes such as HOXB13
Rare, known cancer syndromes such as PTEN, TP53
Testing options:
Single genes
Multi-gene panels
Sequential testing (eg test for common genes first, if negative pursue further testing)

26. Risk for cancer based on Family History

30. Overview of Genetic Testing
Ideally, begin testing with someone who has been diagnosed with cancer
Points to remember:
Family history can evolve over time
Options for genetic testing evolve over time

31. Who to test?

32. Possible genetic test results
POSITIVE:
Mutation in a gene we know a great deal about
Standard screening protocol
Mutation in a newer gene where cancer risks have not yet been well delineated
Unknown screening protocol
NEGATIVE:
True negative: if a known mutation is in the family, a person who tests negative is at the population risk for cancer
Inconclusive: if no mutation known in family, assess risk based on family history
VUS (variant of unknown significance): assess risk based on family history

34. BRCA positive family
Breast cancer risk (general population 1/8 or 12%):
50-85% for BRCA1 and BRCA2
Ovarian cancer risk (general population 1-2%):
44%for BRCA1
27% for BRCA2
Other cancer risks:
BRCA2: male breast cancer, prostate cancer, pancreatic cancer, melanoma

36. Management options if BRCA+
Breast Cancer
Screening: Starting at age 25, self breast exam, twice yearly clinical breast exam, yearly screening breast MRI. Add annual mammography at age 30
Chemoprevention: Tamoxifen, aromatase inhibitor
Prophylactic surgery
Ovarian Cancer
Screening: Starting around age 30, CA-125 blood test and transvaginal ultrasound every 6 months
Chemoprevention: Birth control pills for 3-5 years
Prophylactic surgery to remove ovaries and fallopian tubes
Other cancers if BRCA2+
Annual skin and eye exams for melanoma, prostate cancer screening to start at age 40, pancreatic screening if in family

37. Treatment options: PARP inhibitors
PARP inhibitors are a medication approved by the FDA for the treatment of women who are BRCA positive who have breast or ovarian cancer
Clinical trials ongoing for other types of cancers including prostate cancer and pancreatic cancer
This is one reason for offering BRCA testing to men with metastatic cancer

38. Hereditary Colon Cancer Syndromes
Lynch syndrome (HNPCC)
MLH1, MSH2, MSH6, PMS2, EPCAM genes
Increased risk for colon, uterine, ovarian, and other cancers
3, 2, 1 criteria
Universal tumor screening for Lynch syndrome in colon cancers diagnosed at UVMMC, however this does not pick up 100% of people with Lynch syndrome
Familial adenomatous polyposis (FAP)
APC gene
Other polyposis genes - MUTYH, POLE, POLD1
Other genes with associated colon cancer risk – CHEK2, BRCA1?
Genes associated with genetic syndromes – PTEN, STK11

39. Lynch syndrome – cancer risks

40. Management options for colon cancer syndromes
More frequent colonoscopies: removal of polyps during colonoscopy prevents colon cancer
Lynch: beginning at age 25, every 1-2 years for life
FAP: sigmoidoscopy beginning in the early teens
MUTYH (recessive inheritance): colonoscopy every 1-2 years beginning at age 25-30
Other screenings may include
Uterine and ovarian cancer screening for women
Upper endoscopy
Urinalysis

41. SUMMARY: Looking for CLUES
Age at diagnosis
Pattern in family
Pathology reports
Skin findings
Tumor testing

43. Insurance Issues May need a referral to come for genetic counseling
People with Medicare insurance must meet with a doctor as well as a genetic counselor
GINA – law that protects people against discrimination for health insurance and employment based on genetic information, but does not give protection for life insurance or disability
Genetic testing:
May need to meet criteria for insurance to pay

44. Familial Cancer Program University of Vermont Medical Center Burlington, VT 2nd floor, Hematology/Oncology Laura Colello – Genetic Counselor Wendy McKinnon – Genetic Counselor Dr. Marie Wood – medical oncologist Dr. Marc Greenblatt – medical oncologist Alex - scheduler
** Telemedicine appointments available for families at CVMC (Barre area) and Rutland Regional Medical Center