Download Ovarian cancer at any age

Genetics and Ovarian Cancer
June 16, 2015
Ovarian Cancer Alliance of Oregon and SW Washington
Becky Clark, MS, CGC
Genetic 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
Normal cells
One cell at risk
Tumor develops
First mutation
Second mutation
Autosomal Dominant Inheritance
Parents
Children
50% chance of
inheriting gene change
50% chance of inheriting
unchanged gene
Gene mutations increasing risk for
ovarian cancer
•Hereditary breast and
ovarian cancer syndrome
• BRCA1, BRCA2
•Lynch syndrome
• MLH1, MSH2, MSH6,
PMS2, EPCAM
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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 400
Prevalence 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, MSHS
Becky Clark, MS, CGC
Lisa Clark, FNP, AOCNP, APNG
Phone: 503-297-7403