Transcript Workshop slides - PA Breast Cancer Coalition

Genetics:
For this Generation and the Next
Andrea Forman, MS, LCGC
Fox Chase Cancer Center
Risk Assessment Program
Department of Clinical Genetics
Common Diseases
• Cancer
• Heart disease
• Diabetes
• Hypertension
• Stroke
• Alzheimer's
• Arthritis
• Osteoporosis
Common Risk Factors
• Age
• Family history
• Ethnicity
• Lifestyle
• Diet
• Alcohol
• Smoking
Top 5 Reasons to Know Your
Family History
5. Family recipes should be kept secret —
family medical history should not.
4. Knowing your risk might save your life.
3. It’s free and you don’t have to leave home.
2. It’s a priceless gift to leave to your
children.
1. Because every family has a story, but not
every family has YOUR story.
https://www.yahoo.com/health/10-reasons-you-should-dig-into-your-family-medical-118232923367.html
Genetic information is key
What is a Gene?
DAD
MOM
Family
History
Chance
Lifestyle
Personal
Cancer
Risk
Aging
Genetics
Environment
Cancer and Genetics
Percentage of cancers
that are due to
inherited genetic risk
i.e. 1 out of 10
Fortune Cookie Tip #1
Family history
was the first
genetic test
Clues:
Genetic Risk for Cancer
• YOUNG
– Breast <45, Colon <50
• RARE
– Examples include Ovarian, Male Breast, Pancreatic
• MULTIPLE
– Two or more different cancers in the same person
• FAMILY
– Two or more family members with the same or related types
of cancer.
• Breast/Ovary. Breast/Thyroid/Uterine. Breast/Sarcoma/Brain
Sporadic Family History
Colon, 72
Risk for cancer is
AVERAGE
Familial Family History
Lung, 65
coal miner
Basal Cell
sun exposure
Liver, 50
alcohol abuse
Stomach, 55
H. pylori
Prostate, 75
Risk for cancer is
MODERATE
Lung, 58
smoker
Cervix
HPV, smoker
Hereditary Family History
Breast, 55
Prostate,
59
Breast, 34
Risk for cancer is
HIGH
Ovarian, 44
Breast, 50
Fortune Cookie Tip #2
Don’t forget to
look at both
sides of the
family!
Why would I want to know?
• Possible risk of another, new cancer
• Risks to your children
• Risks to other family members
• Screening and prevention are often
available and may save a life
Family history of breast cancer?
Who is the best person to test?
New
yellow
apple
Red apple tree growing red apples
Courtesy of Kallie Weinan, MS, CGC
Red apple tree growing one yellow apple
Fortune Cookie Tip #3
When searching for something
rare, start the search with the
most likely target.
BRCA1 -
BRCA1 -
BRCA1 +
Does
not want
testing
BRCA1 +
Cancer Risks with HBOC
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
Breast
Ovary
Prostate (male) Breast (male)
Gen. Population
BRCA Carrier
Pancreas
What Can You Do?
Increased screening
• Start Earlier
– 25yo for breast screening
• More Often
– Alternating imaging
every 6 months
• More Aggressive
– Mammogram
+
Breast MRI
Prevention
• Medication
– Tamoxifen
(breast cancer risk)
– Birth control pills
(ovarian cancer risk)
• Surgery
– Risk reducing mastectomy
– Salpingo-oophorectomy
(removal of ovaries and
fallopian tubes)
Guess what?
You won’t be seeing many tests
for just BRCA1/2 anymore
Multi-Gene (NGS) Panels
• Genetic tests to look at dozens of genes
related to cancer
• Similar cost and turn around time as
gene specific testing
• Higher risk of uncertain results
NGS Panels- Breast
Walsh et. al. 2013 (ASHG Platform Presentation)
•800 families with negative BRCA1/2 testing
– 206 tested positive with NGS BROCA panel (26%)
•Of the 26% with a new positive results
–39% (80/206) had BRCA1/2 mutations
–37% carried mutations in CHEK2, PALB2, or TP53
–20% carried mutations in 10 less characterized
genes
Labs offering BRCA1/2
Labs offering NGS panels
Different NGS tests that include
BRCA1/2
Genetic counselors pulling their hair out
Ms. Smith
• 46 year old woman with a newly
diagnosed left breast cancer
– ER/PR+ invasive ductal carcinoma
• Referred to Risk Assessment as patient
wants risk estimate to help her make a
decision about bilateral mastectomy
NGS Test Result
Positive for a gene mutation
• CHEK2
Variants of Uncertain Significance
• BRCA 2
• STK11
Fortune Cookie Tip #4
Sometimes, in
our quest for
answers, we
end up with
more
questions
Moderate Risk Genes
• Cancer risks may not be very high
– How high does risk need to be before we
pursue surgery or medications?
• Cancer risks may be unclear
– How do we make medical decisions when
we don’t know the risks?
• We’re still learning
– The recommendations you get today may
be different in 5 years
NGS Test Result
Positive for a gene mutation
• CHEK2
Variants of Uncertain Significance
• BRCA 2
• STK11
N=398
Rates of Uncertain Variants
Decline in Rate of BRCA1/2 Variants of Uncertain
Significance
40.0%
35.0%
30.0%
All Patients
Middle Eastern
25.0%
Asian
African
20.0%
Native American
15.0%
Latin American
Central European
10.0%
Western European
5.0%
0.0%
2002
2006
2008
2012
Eggington et. al. Current Variant of Uncertain Significance Rates in BRCA1/2 and Lynch Syndrome Testing (MLH1, MSH2,
MSH6, PMS2, EPCAM), March 2012, ACMG Poster Presentation.
Isn’t it just a blood test?
• Positive results
with limited
information
• Inconclusive
results
• Results that don’t
“fit”
• Worry/anxiety
Consider This…
RISKS
BENEFITS
LIMITATIONS
• Anxiety/
distress
• Privacy
• Appropriate
follow-up?
• Clarification
of risk
• Guidance for
medical
management
• Information
for family
• Unclear
results
• Limited data
• Limited
usefulness
• Changes in
technology
What can you do?
• Know your family history
• Educate your family about its history
• Talk to your doctor or a genetic
counselor
What is a Genetic Counselor?
I am a translator
NSGC: www.nsgc.org
Questions?
Andrea Forman, MS, LCGC
Genetic Counselor
Department of Clinical Genetics, Fox Chase Cancer Center
1-877-627-9684
www.fccc.edu/rap
[email protected]