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

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

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

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

Who should consider calling the Familial Cancer Program?

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

Looking for CLUES:

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)

CLUE – pattern of cancers in person or family

Family Tree

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

Sporadic

Family History

More suspicious family history pedigree

CLUE = Pathology Reports Polyps Cancer Dermatology

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

Deeper dive

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)

Risk for cancer based on Family History

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

Who to test?

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

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

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

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

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

Lynch syndrome – cancer risks

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

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

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

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 802-847-8400 ** Telemedicine appointments available for families at CVMC (Barre area) and Rutland Regional Medical Center