Genetics and Ovarian CancerJune 16, 2015

Ovarian Cancer Alliance of Oregon and SW Washington

Becky Clark, MS, CGCGenetic Counselor

Risk for Ovarian cancer

• ~20% of ovarian cancers are related to an inherited cancer syndrome

• ~80% of ovarian cancers are sporadic

Your relative with ovarian cancer

Your risk

None 1%

Mother/Sister 4-6%

Grandmother/Aunt 1-2%

Cancer development

First mutation Second mutation

Normal cells One cell at risk Tumor develops

Autosomal Dominant Inheritance

Parents

Children

50% chance of inheriting unchanged gene

50% chance of inheriting gene change

Gene mutations increasing risk for ovarian cancer

•Hereditary breast and ovarian cancer syndrome

• BRCA1, BRCA2

•Lynch syndrome• MLH1, MSH2, MSH6,

PMS2, EPCAM

• BARD1• BRIP1• CDH1• CHEK2• MRE11A• MUTYH• NBN• PALB2• RAD50• RAD51C• RAD51D• STK11• TP53

Goals of genetic testing

• Understand cause of cancer in family

• Surveillance and prevention of other cancers

• Allow unaffected family members to test• Surveillance• Prevention options• Family planning

Hereditary breast and ovarian cancer syndrome: BRCA1 and BRCA2

Prevalence in the general population: ~1 in 400Prevalence in the Ashkenazi Jewish population: ~ 1 in 40

Consider when history includes one of the following:• Ovarian cancer at any age • Breast cancer at or before age 50• Triple negative breast cancer at or before age 60• Two primary breast cancers in the same person or on the

same side of family• Breast and ovarian cancer in the same person• ≥3 relatives with breast, ovarian, pancreatic cancer and/or

aggressive prostate cancer on the same side of family• Ashkenazi Jewish Ancestry and a personal or family history of

breast, ovarian or pancreatic cancer• Male breast cancer

BRCA mutation cancer risks

General Population BRCA1 or BRCA2 mutation

Breast 12% 40-80%

Ovarian 1% 11-40%

Male Breast 0.1% 1-10%

Prostate 15-18% <30-39%

Pancreatic 0.5% 1-7%

Increased risk for a second primary breast cancer

Reports of increased risk for melanoma

BRCA family tree

Lynch syndrome: MLH1, MSH2, MSH6, PMS2, EPCAM

Consider when history includes one of the following:•Colon cancer before age 50•Uterine cancer before age 50•≥ 2 Lynch cancers in the same person •≥ 2 relatives with a Lynch cancer, one <50 years old•≥ 3 relatives with a Lynch cancer at any age•Abnormal MSI and/or IHC tumor test result

• Performed on colon and uterine tumors

Lynch syndrome cancer risks

General Population Risk Lynch syndrome

Colorectal 5.5% 40-80%

Uterine 2.7% 25-60%

Stomach <1% 1-13%

Ovarian 1.6% 1-24%

Also at increased risk:Small intestine, biliary system (pancreas, liver, bile duct), brain, skin, and urinary tract (kidneys, ureters, bladder, urethra)

Lynch family tree

Genetic testing for ovarian cancer

• Ashkenazi Jewish? Start with the three founder mutations in BRCA1 and BRCA2

• Testing to include BRCA1, BRCA2, and Lynch syndrome

• Recent availability of panel tests: covers BRCA1, BRCA2, Lynch syndrome, and other more rare, lower risk genes

• Single site testing for family members if relative tests positive

Insurance coverage

• Covered benefit if medical criteria is met (NCCN criteria). Some insurance have their own criteria.

• Always pre-authorized by the genetic testing lab

• Out of pocket cost depends on your insurance plan

• Discounted prices for those without insurance coverage

Laws that protect against genetic discrimination in health insurance and employment

• HIPAA: Health Insurance Portability and Accountability Act

• Federal law • GINA (Genetic Information Non-Discrimination Act) 2008• Applies to family history and genetic test results• Does not cover life insurance, long-term disability

• State laws• Oregon law DOES cover life insurance and long-term

disability• Applies to genetic test results, not family history

Types of results from genetic testing

• Negative: no mutation detected • Base cancer risks on family history

• Positive: mutation detected that causes an increased risk for cancer• Follow management guidelines for care• Offer genetic testing to other family members

• Variant of uncertain significance (VUS):• Change identified, but not enough evidence to determine if

disease causing or benign • Identified in ~10% of tests• Cannot test family members. Exception: Family Studies

Programs• VUS will be reclassified over time

Thinking about the future

• DNA banking• Store DNA at a facility for future testing

• Fertility preservation and family planning• Freezing eggs• Pre-implantation Genetic Diagnosis (PGD)• Prenatal testing (amniocentesis)

Contact

Compass Oncology GREAT Program

Genetic Risk Evaluation & Testing

Lucy Langer, MD, MSHSBecky Clark, MS, CGCLisa Clark, FNP, AOCNP, APNG

Phone: 503-297-7403