Kayla York MS LCGC Licensed Genetic Counselor Avera Cancer Institute Outline Genetic Counseling Cancer Genetics BreastOvarian Cancer ColonEndometrial Cancer Summary Genetic Counseling ID: 554593
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Slide1
Genetic Counseling and testing for Cancer
Kayla York, MS, LCGC
Licensed Genetic Counselor
Avera Cancer InstituteSlide2
Outline
Genetic Counseling
Cancer Genetics
Breast/Ovarian Cancer
Colon/Endometrial Cancer
SummarySlide3
Genetic CounselingSlide4
Genetic Counseling
Genetic counselors are health professionals with specialized graduate degrees and experience in the areas of medical genetics and counseling.
Genetic counseling is the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease. This process integrates:
Interpretation of family and medical histories to assess the chance of disease occurrence or recurrence.
Education about inheritance, testing, management, prevention, resources and research.
Counseling to promote informed choices and adaptation to the risk or condition.
National Society of Genetic Counselors, 2005Slide5
Genetic Counseling
Cancer Genetic Counseling
Educate patients and their families as well as provide emotional support:
Cancer risks
Options for genetic testing
Options for cancer screeningSlide6
Genetic Counseling
Initial Visit
Personal History
Family History (
both mother’s and father’s side
)
Risk Assessment
Discussion of genetics and specific genes
Discussion of possible test results
Discussion of impact of genetic testing
Insurance/GINA
Arrange testing as needed
Result Disclosure
Follow-up visits as neededSlide7
Cancer GeneticsSlide8
Cancer GeneticsSlide9
Cancer GeneticsSlide10
Cancer GeneticsSlide11
Cancer Genetics
Genetics
Genetics
Lifestyle and
Environment
Lifestyle and
Environment
Lifestyle and
Environment
High Risk Genes
Low Risk Genes
SporadicSlide12
Cancer Genetics
Cluster of specific types of cancers/ same cancer
Young ages at diagnosis
Individuals with multiple or bilateral cancers
Rare cancers
Pattern of inheritance in the family
Certain ethnic groups have higher frequencies of specific genetic disordersSlide13
Cancer Genetics
BRCA1/BRCA2
: Breast and Ovarian
Lynch Syndrome
: Colorectal, Endometrial, GI
Other Syndromes
Familial Adenomatous Polyposis (FAP)
: Colon polyps, Colorectal, Stomach and Pancreatic
MEN1
: Parathyroid, pituitary, pancreas
MEN2:
Medullary thyroid Cancer
Li
Fraumeni
Syndrome
(Tp53)
: soft tissue sarcoma, osteosarcoma, breast cancer, brain tumors, adrenocortical carcinoma
RET
:
Medullary
thyroid,
pheochromocytomas
, parathyroid adenomas
Cowden Syndrome (
PTEN)
: Breast cancer, uterine cancer, thyroid cancer, benign findings (colon polyps, thyroid nodules,
macrocephaly
, etc)
Peutz
Jeghers
Syndrome (STK11): Colon polyps, breast cancer, pancreatic cancer, colon cancer, ovarian cancer, germ cell cancers
Hereditary Diffuse Gastric Cancer and Lobular breast cancer (CDH1): Gastric cancer and lobular breast cancer
MYH- Associated Polyposis: Colon polyps, Colorectal cancerSlide14
Breast and Ovarian CancersSlide15
Breast Cancer
Most common cancer in women
1 in 8 women will develop breast cancer in their lifetime
1 in 1000 men will develop breast cancer in their lifetime
5-10% of all women with breast cancer carry an inherited genetic predisposition
15-20% of all men with breast cancer carry an inherited genetic predispositionSlide16
Ovarian Cancer
Ovarian cancer is the 5
th
most common cancer for women
1 in 72 women will develop ovarian cancer in their lifetime
Approximately 10- 20% of women with ovarian cancer have an inherited gene predispositionSlide17
Breast and Ovarian Cancers
Risk Factors- Both
Age
Parity
Menarche (≤ 11)
Menopause (≥55)
Alcohol
Weight
Physical Activity
Family
History
Risk Factors- Breast
Previous chest radiation
Hormone Therapy
Breast
Conditions
Atypia/Hyperplasia
LCISSlide18
Breast Cancer
Only a fraction of breast cancers are caused by an inherited gene mutationSlide19
Breast Cancer
Genetics
Genetics
Lifestyle and
Environment
Lifestyle and
Environment
Lifestyle and
Environment
High Risk Genes
Low Risk Genes
SporadicSlide20
Hereditary Breast Cancer Predisposition SyndromesSlide21
Family #1
Breast 42
Triple Neg Breast 40
Breast 38
Ovarian 50
Ovarian 40Slide22
Cancer Genetics
Cluster of specific types of cancers/ same cancer
Young ages at diagnosis
Individuals with multiple or bilateral cancers
Rare cancers
Pattern of inheritance in the family
Certain ethnic groups have higher frequencies of specific genetic disordersSlide23
Family #1
Breast 42
Triple Neg Breast 40
Breast 38
Ovarian 50
Breast 38
Ovarian 48
Ashkenazi Jewish
German
German
Norwegian
BRCA1 mutationSlide24
BRCA1 and BRCA2
BRCA1
and
BRCA2
are the most common genes that predispose to breast and ovarian cancer when a mutation is present.
Approximately 2-3% of women with breast cancer carry a mutation in
BRCA1
or
BRCA2
Approximately 10% of women with ovarian cancer carry a mutation in
BRCA1
or
BRCA2Slide25
BRCA1 and BRCA2
Lifetime
risk for breast cancer 56%-80%
More commonly triple negative breast cancer
Lifetime risk for ovarian cancer up to 44%
For Men:
Lifetime risk for male breast cancer 2%
Lifetime risk for prostate cancer 20
%
For Men and Women
Lifetime risk for Pancreatic cancer 2-4%
Lifetime
risk for breast cancer 56%-80%
Lifetime risk for ovarian cancer 11-27%
For Men:
Lifetime risk for male breast cancer 8%
Lifetime risk for prostate cancer 32%
For Men and Women:
Lifetime risk for pancreatic cancer: 5-8%
Lifetime risk for melanoma: 5%
BRCA1
BRCA2Slide26
Hereditary Breast Cancer Syndromes
Management: BRCA1/BRCA2
Women: Breast Cancer
Breast Awareness starting at age 18
Clinical Breast Exam starting at age 25 every 6-12 months
Annual Breast MRI starting at age 25 or individualized based on family history
Annual Mammogram starting at age 30 or individualized based on family history
Discuss prophylactic bilateral mastectomies
Women: Ovarian Cancer
Recommend
salpingo-oophorectomy
, ideally between the ages of 35-40 or individualized based on family history and when child bearing is complete
Data is limited but Providers can consider concurrent transvaginal ultrasound + CA-125 every 6 months starting at age 30 or based on family history
NCCN guidelines
2.2016Slide27
Hereditary Breast Cancer Predisposition Syndromes
High Risk Genes
Cowden syndrome: PTEN Hamartoma Syndrome
Breast, Uterine, and Thyroid cancers
Macrocephaly
and benign findings ( ex: thyroid disorders, colon polyps, and dermatological findings)
Li
Fraumeni
Syndrome: Tp53 gene
Breast, sarcoma, brain tumors,
adrenocortical
carcinoma, leukemia, lung
bronchoalveolar
cancers
Multiple primaries
Diffuse Gastric cancer and Lobular breast cancer: CDH1 gene
Diffuse gastric cancer and lobular breast cancerSlide28
Hereditary Breast Cancer Predisposition Syndromes
Moderate Risk Genes:
PALB2
CHEK2
ATM
These genes are well studied with lifetime risks for breast cancer of 20%-56%. They have also been shown to increase the risks for other cancers
NCCN
Guidelines (2.2016)
Annual Mammogram and Breast MRI starting at age 30 or individualized based on family history
Prophylactic mastectomy is an option with mutations in
PALB2
Discussion of prophylactic bilateral mastectomies for mutations in
ATM
or
CHEK2
is controversial and is based on family history and personal
historySlide29
Hereditary Breast Cancer Predisposition Syndromes
Newer Genes:
RAD51D
RAD51C
RAD50
NBN
BRIP1
BARD1
FANCC
MRE11A
These genes are known to have an association with an increased risk for breast and other cancers but they are not as well studied and data is based on a small number of patients. The precise lifetime risks for cancers have not been determined nor have the spectrum of cancers associated with mutations in these genes.Slide30
Hereditary Breast Cancer Predisposition SyndromesSlide31
Family #2
Breast 44
Breast 53
Breast 47
Endometrial 41
d. 60s
83
Endometrial 70s
Colon 60s
Polyps
d. 80s
Breast 40sSlide32
Family #2
Breast 44
Breast 53
Breast 47
Endometrial 41
d. 60s
83
Endometrial 70s
Colon 60s
Polyps
d. 80s
Breast 40s
BRCA1/2 NEG
HC: 59cm; thyroid nodules and goiter
PTEN
mutSlide33
Cowden Syndrome: PTEN
PTEN gene
Tumor suppressor gene located on Chromosome 10
Responsible for control of cell division as well as other functions
The exact
prevalance
of PTEN/Cowden syndrome is unknown
Lifetime risk for breast cancer = 85%
Also associated with uterine cancer, thyroid cancer, kidney and colon cancers as well as thyroid nodules, colon polyps,
trichilemmomas
, and
macrocephalySlide34
Family #3
Breast 47
Breast 58
Breast 50
Pancreatic 60
Prostate 55Slide35
Family #3
Breast 47
Breast 58
Breast 50
Pancreatic 60
Prostate 55
BRCA2Slide36
Family #4
Breast 35
Breast 55
Breast 50
Breast 40Slide37
Family #4
Breast 35
Breast 55
Breast 50
Breast 40
BRCA1/2; TP53; PTEN; STK11; and CDH1 = NEGSlide38
Family #5Slide39
Family #5
RAD51CSlide40
RAD51C
RAD51C is a newer gene that has been mostly associated with ovarian cancer risk
Estimated to confer a 10-15% lifetime risk for ovarian cancer
NCCN guidelines (2.2016) recommend consideration of risk reducing
salpingo
-oophorectomySlide41
Colon CancerSlide42
Colon Cancer
3
rd
most common cancer
1 in 20 individuals will develop colon cancer in their lifetime
S
lightly higher incidence in men than womenSlide43
Colon Cancer
Risk Factors
Age
Phx of colon polyps
Phx of Inflammatory Bowel Disease
Type 2 diabetes
Diet high in red meats and processed meats
Risk Factors
Smoking
Alcohol
Weight
Physical Activity
Family HistorySlide44
Hereditary Colon Cancer Predisposition SyndromesSlide45
Col 40, 50
Breast 55
Endo 40
2 adenomas
2 Adenomas
Col 50
Endo 35
Col 45
Col 40
Panc 60
Family #1Slide46
Colon 60
2 Adenomas
Col 60
Col 80
1 Adenoma
83
Family #2Slide47
Colon 45
20 adenomas
Colectomy 40
100+ polyps
Family #3
#
#
No informationSlide48
Family #4
Colon 45
Dx 54
Dx 70
Dx 40s
Dx 40s
Dx 71
Dx 57
Dx 80
Dx 60 Dx 40 Dx 67
Dx 50
3
Dx 75
Dx 60
Dx 70s
Endometrial
Bladder
Pancreatic
Breast
Prostate
ColorectalSlide49
Hereditary Colon Cancer Predisposition Syndromes
Pt meets Bethesda criteria
Pt meets Amsterdam criteria
>10 adenomas in same individual
Individual with multiple GI
hamartomatous
polyps, Juvenile polyps or serrated polyposis syndrome
Individual with a
desmoid
tumor
NCCN Guidelines 4.2013Slide50
Hereditary Colon Cancer Predisposition Syndromes
Polyposis Syndromes
Generally >20 colon polyps in a lifetime
Non-Polyposis Syndromes
Generally <20 colon polyps in a lifetime
There can be overlap between the two- especially with attenuated forms of polyposis syndromesSlide51
Amsterdam II CriteriaAt least 3 relatives must have a cancer associated with HNPCC/Lynch Syndrome and all of the following criteria should be present:
One must be a first degree relative of the other two
At least 2 successive generations affected
At least one of the relatives with cancer associated with HNPCC should be diagnosed before age 50
FAP should be excluded in the colorectal cancer cases
Tumors should be verified whenever possible
Hereditary Colon Cancer Predisposition SyndromesSlide52
Hereditary Colon Cancer Predisposition Syndromes
Bethesda Criteria
Tumors from individuals should be tested for MSI in the following situations:
Colorectal cancer diagnosed less than 50 years of age
Presence of synchronous, or
metachronous
colorectal or other LS- associated tumors, regardless of age
Colorectal cancer with histology suggestive of MSI-H in a patient less than 60 (tumor infiltrating lymphocytes,
Crohn’s
like lymphocytic reaction,
mucinous
/signet-ring differentiation, or
medullary
growth pattern)
Colorectal cancer in a patient with ≥ 2 first or second degree relatives with a Lynch syndrome related cancers regardless of ageSlide53
Hereditary Colon Cancer Predisposition Syndromes
Sjursen
et al [2010]
found the sensitivity of the Amsterdam II criteria to be 87% (
MLH1
), 62% (
MSH2
), 38% (
PMS2
), and 48% (
MSH6
) for identifying individuals with a germline mutation.
Hampel
et al [2005]
also reported that in a population-based study of persons with colon cancer, only three of 23 persons with a germline mutation in an MMR gene met the Amsterdam criteria. Slide54
Hereditary Colon Cancer Predisposition Syndromes
IHC-MMR Tumor Testing
Screens the tumor for Lynch syndrome
Analyzes presence or absence of 4 proteins
MLH1, MSH2, MSH6, PMS2
95% of individuals with Lynch syndrome will have absence of at least 1 protein on IHC-MMR
Absence of staining could indicate a germline mutation
At Avera- done on all colon cancer resections and endometrial cancers at time of surgerySlide55
Hereditary Colon Cancer Predisposition Syndromes
Lynch SyndromeSlide56
Hereditary Colon Cancer Predisposition Syndromes
FAP/Attenuated FAP
Caused by mutations in the
APC
gene
Classic FAP is associated with 100s-1000s of polyps in the teens-30s
The risk for colon cancer for untreated individuals is ~87% by age 45 and 93% by age 50
Attenuated FAP is associated with <100 polyps and older age at onset. The risk for colon cancer is ~70% to age 80
MYH
-Associated
Polyposis
Autosomal
Recessive
polyposis
disorder caused by mutations in the
MYH
gene
10s-100s of polyps
Lifetime risk for colon cancer 43%-100%Slide57
Hereditary Colon Cancer Predisposition Syndromes
Peutz
Jeghers
Syndrome
STK11 gene
Breast, Ovarian (often sex cord tumors), pancreatic, and colon cancers
Colon polyps and oral freckling (mouth and lips)
Juvenile
Polyposis
Syndrome
SMAD4 and BMPR1A genes
Juvenile polyps of the colon
Colon cancerSlide58
Hereditary Colon Cancer Predisposition SyndromesSlide59
Col 40, 50
Breast 55
Endo 40
2 adenomas
2 Adenomas
Col 50
Endo 35
Col 45
Col 40
Panc 60
Family #1
MSH2Slide60
Colon 60
2 Adenomas
Col 60
Col 80
1 Adenoma
83
Family #2
PMS2 absent IHC
PMS2 mutSlide61
Colon 45
20 adenomas
Colectomy 40
100+ polyps
Family #3
#
#
No information
APC +
22yo
10 polyps
20yo
20 polyps
15yo
12yo
APC +Slide62
Family #4
Dx 45
Dx 54
Dx 70
Dx 40s
Dx 40s
Dx 71
Dx 57
Dx 80
Dx 60 Dx 40 Dx 67
Dx 50
3
Dx 75
Dx 60
Dx 70s
Endometrial
Bladder
Pancreatic
Breast
Prostate
Colorectal
Normal IHC
25 gene panel =
MSH6 VUSSlide63
Variant of Uncertain Significance
VUS: A variant of uncertain or unknown significance is a change in the DNA sequence of the gene where it is unknown if it damages the gene or not.
DNA Change
Classification
Deleterious
Mutation
Positive Result=
Damaging change to the gene
VUS- Suspected Deleterious
Evidence
points to most likely damaging/positive
Variant
of Uncertain/Unknown Significance
Unknown
if damaging or benign change
VUS- Likely Benign
Evidence points to most
likely negative/benign
Benign Polymorphism
Negative
Result- does not affect gene functionSlide64
Family #4
Dx 45
Dx 54
Dx 70
Dx 40s
Dx 40s
Dx 71
Dx 57
Dx 80
Dx 60 Dx 40 Dx 67
Dx 50
3
Dx 75
Dx 60
Dx 70s
Endometrial
Bladder
Pancreatic
Breast
Prostate
Colorectal
Normal IHC
25 gene panel =
MSH6 VUS
ATM VUS
ATM VUS- likely benign
No AnswerSlide65
Hereditary Colon Cancer Predisposition
Management:
Lynch Syndrome- Depends on the gene involved
Colonoscopies 1-2 years starting at age 20-25 or individualized based on family history
Consider EGD every 3-5 years starting at age 30-35 (
MLH1/MSH2
)
Prophylactic TAH/BSO when childbearing is complete
Consider annual urinalysis starting at age 30-35
Consider annual physical/neurological examSlide66
Hereditary Colon Cancer Predisposition
Management
Classic FAP
Annual Colonoscopy starting at age 10-15
Proctocolectomy
or Colectomy: Age at surgery depends on polyp load and severity of family history
Attenuated FAP
Colonoscopy every 1-2 years with consideration of colectomy depending of polyp burden
Extracolonic
surveillance:
Upper
Endoscopy starting at age 20-25- earlier if colectomy prior to age 20
Annual Physical exam
Annual abdominal exam with consideration of CT or MRI
Annual thyroid examSlide67
SummarySlide68
Summary
Approximately 5-10% of all cancers are caused by a hereditary gene mutation
Family history is an important tool for identifying these families
Management guidelines and recurrence risks may differ significantly if a patient has a hereditary cancer syndromeSlide69
Questions?