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Comprehensive Cancer Panel
Hereditary Cancer Testing
KNOWING WHAT TO LOOK FOR KNOWING WHERE TO LOOK AND KNOWING WHAT IT MEANS
Can cancer be hereditary?
Cancer occurs when normal cells begin to grow uncontrollably, forming
a malignant tumor. While cancer is quite common (with about one in
three individuals developing some form of cancer in their lifetime),1
most cancer is not hereditary. However, some individuals develop
cancer as a result of a harmful change, also known as a pathogenic
variant, in a gene that can be passed down from generation to
generation. In general, it is estimated that approximately 5-10% of
breast cancer, 5% of colorectal cancer, up to 25% of ovarian cancer,
up to 10% of pancreatic cancer, and at least 3% of endometrial cancer
are due to pathogenic variants associated with hereditary cancer
susceptibility.2,3,4,5,6,7
Who should consider genetic testing for
hereditary cancer?
For some well-described hereditary cancer syndromes, criteria exist
based on personal medical and family histories to help identify at-risk
patients. In many cases, however, patients do not meet the clinical
diagnostic criteria, or the criteria may overlap for multiple conditions,
making it difficult to decide which genes should be tested and in what
order. Therefore, your healthcare provider or genetic counselor can help
decide which test is best for you.
GUIDE FOR HEREDITARY CANCERS: COMPREHENSIVE PANEL
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Clinical Indications for the Comprehensive Cancer Panel
The Comprehensive Cancer Panel is appropriate for individuals
whose personal and/or family history are suggestive of a
hereditary predisposition to cancer.
Common indications for hereditary cancer testing:
•A
personal and /or family history of cancer at a young age.
Generally, cancers diagnosed prior to age 50 prompt suspicion
of a hereditary predisposition.
• Two or more primary cancers in an individual, either of the
same origin (e.g., bilateral breast cancer or multiple colon
cancers) or of different origin (e.g., breast and ovarian or colon
and endometrial cancers).
• A pattern of cancer in which the individuals with similar
or related cancers are on one side of the family, spanning
multiple generations.
Situations in which the Comprehensive Cancer Panel is
particularly beneficial:
•W
hen there is concern for more than one hereditary cancer
syndrome. For example, if the family history includes more than
one person with ovarian cancer, this may be associated with
a breast/ovarian cancer syndrome (BRCA1 or BRCA2), Lynch
syndrome (MLH1, MSH2, MSH6, PMS2, and EPCAM), or a
gene more recently described to be associated with ovarian
cancer risk.
• The family history includes a number of cancer cases, but they
are of several different types. Therefore, the pattern does not
seem to fit any one hereditary cancer syndrome in particular.
• A prior single gene or subpanel test was negative and there are
remaining genes available on the Comprehensive Cancer Panel
that may explain the family history.
2
What genes are covered by the Comprehensive
Cancer Panel and what are the associated cancer
risks?
The Comprehensive Cancer Panel at GeneDx includes analysis of 32
genes associated with a hereditary predisposition to breast, ovarian,
colorectal, endometrial, pancreatic, and other various cancers. This
analysis includes evaluation for the most common hereditary cancer
syndromes, such as Hereditary Breast and Ovarian Cancer (HBOC)
and Lynch syndrome. Identifying patients at increased risk of
developing cancer due to a hereditary cancer syndrome can allow
for early detection or prevention of cancer.
The 32 genes included in the Comprehensive Cancer Panel are APC,
ATM, AXIN2, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1,
CDK4, CDKN2A, CHEK2, EPCAM, FANCC, MLH1, MSH2, MSH6,
MUTYH, NBN, PALB2, PMS2, POLD1, POLE, PTEN, RAD51C,
RAD51D, SCG5/GREM1, SMAD4, STK11, TP53, VHL, and XRCC2.
These genes can be categorized into three main groups: High-Risk,
Moderate-Risk and Newer-Risk Genes as described in Table 1.
High-Risk Genes
Moderate-Risk Genes
• Genes included: APC,
BMPR1A, BRCA1, BRCA2,
CDH1, CDKN2A, EPCAM,
MLH1, MSH2, MSH6, MUTYH,
PMS2, PTEN, SMAD4, STK11,
TP53, VHL
• Genes included: ATM, CHEK2,
PALB2
• Well studied
• Well studied
• Approximately two- to fourfold risk of developing one or
more cancers
• May increase risk for other
cancers
• Greater than four-fold risk
of developing one or more
cancers
• Can cause a moderate risk for
other cancers
• Limited guidelines for
screening and prevention
• Guidelines for screening and
prevention established
Newer-Risk Genes
• Genes included: AXIN2,
BARD1, BRIP1, CDK4, FANCC,
NBN, POLD1, POLE, RAD51C,
RAD51D, SCG5/GREM1,
XRCC2
• Not as well studied; data
based on small number of
patients or patients within a
specific ethnicity
• Precise lifetime risks and
tumor spectrum not yet
determined
• Guidelines for screening and
prevention not yet established
Table 1: Composition of Comprehensive Cancer Panel
Each of the genes on the Comprehensive Cancer Panel is
associated with one or more cancers as described in Table 2.
GUIDE FOR HEREDITARY CANCERS: COMPREHENSIVE PANEL
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High-Risk Genes
ModerateRisk Genes
Newer-Risk Genes
Genes Tested
Associated Cancers and Risks*
APC
Colorectal (up to 93%), Duodenal or perlampulary (5%), Gastric, Thyroid, Pancreatic, Brain, Liver
BMPR1A
Colorectal (40-50%), Gastric (up to 21% if gastric polyps)
BRCA1
Female Breast (57-87%), Ovarian (24-54%), Prostate, Male Breast, Pancreatic, Fallopian tube, Primary
peritoneal, Endometrial (serous)
BRCA2
Female Breast (41-84%), Prostate (20-34%), Ovarian (11-27%), Pancreatic (5-7%), Male Breast (4-7%),
Melanoma, Fallopian tube, Primary peritoneal, Endometrial (serous)
CDH1
Diffuse gastric cancer (40-83%), Female Breast (39-52%), Colon
CDKN2A
Melanoma (28-76%), Pancreatic (17%)
EPCAM**
Colorectal (69-75%), Endometrial (12-55%), Ovarian, Gastric, Pancreatic, Biliary tract,
Urothelium, Small bowel, Brain, Sebaceous neoplasms
MLH1
Colorectal (22-80%), Endometrial (31-54%), Ovarian (13-20%), Gastric (6-20%), Pancreatic, Biliary tract,
Urothelium, Small bowel, Brain, Sebaceous neoplasms
MSH2
Colorectal (22-80%), Endometrial (31-61%), Ovarian (10-24%), Gastric (<1-9%), Pancreatic, Biliary tract,
Urothelium, Small bowel, Brain, Sebaceous neoplasms
MSH6**
Colorectal (20-44%), Endometrial (44%), Ovarian (1-11%), Gastric, Pancreatic, Biliary tract, Urothelium, Small
bowel, Brain, Sebaceous neoplasms
MUTYH
Colorectal (80%), Duodenal (4%), Endometrial
PMS2**
Colorectal (15-20%), Endometrial (15%), Ovarian, Gastric, Pancreatic, Biliary tract, Urothelium, Small bowel,
Brain, Sebaceous neoplasms
PTEN
Female Breast (25-50%), Thyroid (10%), Endometrial (5-10%), Colon, Renal, Melanoma
SMAD4
Colorectal (40-50%), Gastric (up to 21% if gastric polyps)
STK11
Female Breast (32-54%), Colorectal (39%), Pancreatic (11-36%), Gastric (29%), Ovarian tumors (21%), Lung
(15%), Small intestine (13%), Cervical (10%), Endometrial (9%), Testicular tumors (9%)
TP53
Female Breast, Soft tissue sarcoma, Osteosarcoma, Brain, Hematologic malignancies,
Adrenocortical carcinoma. Overall risk for cancer: nearly 100% in females, 73% in males
VHL
Clear cell renal cell carcinoma (up to 70%), Pancreatic neuroendocrine tumors (5-17%), other characteristic
tumors include hemangioblastomas and pheochromocytomas
ATM
Female Breast, Colon, Pancreatic
CHEK2
Female Breast, Male Breast, Colon, Prostate, Thyroid, Endometrial (serous), Ovarian
PALB2
Female Breast (25-58%), Male Breast, Pancreatic, Ovarian
AXIN2
Colon
BARD1
Female Breast, Ovarian
BRIP1
Female Breast, Ovarian
CDK4
Melanoma, Non-melanoma skin cancer, Pancreatic
FANCC
Female Breast
NBN
Female Breast, Melanoma, Non-Hodgkin lymphoma
POLD1
Colon, Endometrial
POLE
Colon
RAD51C
Female Breast, Ovarian
RAD51D
Female Breast, Ovarian
SCG5/GREM1
Colon
XRCC2
Female Breast, Pancreatic
*Risks provided when available
**Tumor spectrum is representative of Lynch syndrome; data are limited with regard to the association of certain cancers with pathogenic variants in
MSH6, PMS2, and EPCAM.
Table 2: Cancers and Lifetime Risks Associated with Genes in the Comprehensive Cancer Panel
4
How are cancer risk genes inherited?
Genes provide the instructions for
normal cell growth and development.
We have two copies of every gene,
one copy that we get from our
Affected
mother and one copy from our
Unaffected
father. Most genetic changes that
cause a hereditary form of cancer are
inherited in an autosomal dominant
manner. In a dominant condition, a
pathogenic variant in just one copy of
Affected Unaffected Unaffected Affected
son
daughter
son
daughter
the gene can lead to symptoms of the
Adapted from U.S. National Library of Medicine
condition, in this case, an increased
risk of cancer. Since we only give one copy of each gene to our
children, if a person has a dominant condition, there is a 50% chance
to pass down the variant to each child, male or female. Siblings of an
individual with a pathogenic variant also have up to a 50% chance to
have the same variant. The risk for other family members to carry the
same pathogenic variant depends on how closely they are related to
an affected individual. It is important to remember that not all people
who inherit a pathogenic variant in one of their genes will develop
cancer, however, the risk does increase.
Autosomal Dominant
Unaffected
father
Affected
mother
A minority of cancer-related genes are inherited in an autosomal
recessive manner. In an autosomal recessive condition, both copies of
the gene have a pathogenic variant (one
Autosomal Recessive
from each parent). Individuals with this
Carrier
Carrier
father
mother
type of condition will always pass on one
variant to their offspring. In other words,
all of their offspring will be carriers.
Affected
Unaffected
However, in order for their offspring
Carrier
to have the condition, their partner
must also be a carrier of at least one
pathogenic variant in the same cancerrelated gene. As such, most individuals
Affected
Carrier
Carrier
Non-Carrier
with recessive conditions are at low risk
Unaffected Unaffected Unaffected
to have an affected child.
Adapted from U.S. National Library of Medicine
GUIDE FOR HEREDITARY CANCERS: COMPREHENSIVE PANEL
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What can I expect to learn from genetic testing
for hereditary cancer?
There are three possible outcomes of genetic testing: positive, negative
and variant of uncertain significance (VUS). All patients who undergo
genetic testing should receive pre-test and post-test genetic counseling
to understand the implications of testing. Genetic counseling services
across the country can be found at: www.nsgc.org
Positive Result
A positive (pathogenic variant) result means that a variant was identified
that causes an increased risk to develop
cancer. Knowledge of a positive result
provides valuable information to the patient,
physician and family members. Knowledge
of a patient’s increased risk can assist in
making medical management and treatment
decisions with the goals of early detection
and/or cancer prevention. Furthermore,
testing the patient’s family members can
allow for accurate predictions of cancer risks.
Oncology Genetic Test Report
BRCA1/2 Sequencing and Deletion Duplication Analysis
PHYSICIAN
PAT I E N T
Dr. XYZ Oncology Center
DOB: 02/21/1983
X1111
P: 123-456-7890
SAMPLE
SAMPLE PATIENT
123 MAIN ST
ANYTOWN, NJ
Specimen ID: 1111111111
Age: 28
Date of Report: 4/29/2011
Sex: F
Date Received: 4/25/2011
12345
Patient ID: 111111
M1
Address: 555 MAIN ST
F: 123-456-7890
Date Collected: 4/25/2011
Source: Blood
ANYTOWN, NJ
OncogeneDx: BRCA1/2 Sequencing and Deletion Duplication Analysis
Results Summary: POSITIVE
Gene
Results
Classification
BRCA1
c.68_69delAG (aka 185delAG or 187delAG)
(p.Glu23ValfsX16)
PATHOGENIC
This individual is heterozygous for a deletion of 2 nucleotides in exon 2 of the BRCA1 gene. The normal sequence with the bases
that are deleted in braces is: ATCTT{AG}AGTGT. This mutation is denoted c.68_69delAG at the cDNA level or at the protein level
as p.Glu23ValfsX16. This result is consistent with a diagnosis of Hereditary Breast and Ovarian Cancer.
No other disease-causing mutations/changes were detected in the BRCA1 or BRCA2 genes by DNA sequencing or deletion/
duplication analysis.
Lifetime Cancer Risks
• Lifetime cancer risks due to a BRCA1 mutation include: approximately 57% - 84% risk for breast cancer in women and 24% 54% risk for ovarian cancer (Antoniou 2003, Chen 2007, Ford 1998), 3% risk for pancreatic cancer (The Breast Cancer Linkage
Consortium 1999), a 20% risk for prostate cancer (Thompson 2002), and 4% risk for male breast cancer (Liede 2004).**
**Only the most commonly associated cancer risks are listed.
Recommendations
• Genetic counseling is recommended to discuss the implications of this test result for the patient and his/her family members.
• The first degree relatives of this patient have a 50% chance of also testing positive for the mutation(s) identified.
• The NCCN Guidelines for Genetic/Familial High-Risk Assessment (v.1.2013) include management recommendations for HBOC.
• To learn more information about your results, please visit: www.oncogenedx.com/positive
Comments on Results
Gene
Results
Classification
cDNA RefSeq
BRCA1
c.68_69delAG (aka
185delAG or 187delAG)
PATHOGENIC
NM_000000.0
Interpretation: This mutation causes a frameshift starting with codon Glutamic acid at position 23, which changes this amino
acid to a Valine residue, and creates a premature Stop codon at position 16 of the new reading frame. This mutation is predicted
to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.68_69delAG
mutation is known to be a founder mutation in the Ashkenazi Jewish population and is associated with Hereditary Breast and
Ovarian Cancer (Struewing 1995).
Page: 1 of 3
Report Electronically Signed by:
J. Weisberger, M.D.
Molecular Pathologist
Report Electronically Signed by:
First Name, Last Name, MS, CGC
Certified Genetic Counselor
GeneDx 207 Perry Parkway Gaithersburg, MD 20877
P (888) 729-1206 F (301) 710-6594
Sherri J. Bale Ph.D., FACMG
Laboratory Director
genedx.com/oncology
Negative Result
A negative result means that a pathogenic variant was not identified.
This result can have different implications, depending on the specific set
of circumstances related to the testing (e.g., whether or not there is a
known pathogenic variant in the family). It is important to speak with a
healthcare provider or genetic counselor to learn about the significance
of negative genetic testing results in light of an individual’s own medical
and family history.
Variant of Uncertain Significance (VUS)
A variant of uncertain significance (VUS) indicates that the effect of
the variant cannot be clearly established. To further clarify the clinical
significance of this variant, testing of family members may be helpful.
If a relative with a related cancer is found to have the same variant, it
may provide evidence that the variant is pathogenic. The greater the
6
POSITIVE
number of affected family members who carry the VUS, the greater
the likelihood that the VUS is harmful. If the VUS continues to be found
in family members with related cancers, in addition to other evidence,
the variant may be reclassified as pathogenic. At that time, predictive
genetic testing can then be offered to extended family members.
Conversely, a VUS could be determined to be benign through this and
other research. GeneDx can review a patient’s detailed family history
to determine if family members are eligible for complementary targeted
variant testing through our Variant Testing Program.
BRCA1 Positive
Information for Patients Who Have Tested Positive for a Disease-Causing Mutation
Your Genetic Test Results:
You have undergone genetic testing of the BRCA1 gene, which is associated with hereditary breast and ovarian cancer (HBOC). Your test was
positive for a change, or mutation, in this gene, which is associated with an increased risk to develop breast, ovarian and other cancers.
How long does it take to get
results?
What This Test Result Means...
For You:
If you have had a diagnosis of breast, ovarian, or pancreatic cancer, this
test result provides a genetic explanation for why you developed cancer.
100
Breast and Ovarian Cancer Risk
by Age Associated with BRCA1 Mutations
Breast Cancer Risk
80
Ovarian Cancer Risk
81%
69%
58%
60
54%
46%
39%
40
40%
21%
21%
20
3%
3%
0
0%
40
30
60
50
70
80
Age
Adapted from King MC et al. Breast and ovarian cancer risks due
to inherited mutations in BRCA1and BRCA2.
Science. 2003 Oct;302(5645):643-6.
100
80
Probability (%)
Women who test positive for a BRCA1 mutation, have a 57 to 84% chance
to develop breast cancer at some point in their life. Women who have had
breast cancer and test positive for a BRCA1 mutation are at increased risk
for a second primary breast cancer. This is not a recurrence of the original
breast cancer but a brand new breast cancer. The chance to develop ovarian
cancer is also higher than in the average woman. The lifetime risk to develop
ovarian cancer is between 24 and 54% for women who carry a mutation in
the BRCA1 gene. The chance to develop breast and ovarian cancer begins
increasing when a woman is in her mid 30’s. There are other types of cancers
associated with a BRCA1 mutation, such as male breast cancer, prostate
cancer and melanoma (skin cancer) and pancreatic cancer in both men and
women. Although increased compared to people who do not have a BRCA1
mutation, the risks of these cancers are much lower than the risk of breast
and ovarian cancers in BRCA1 carriers. You should discuss these results with
your doctor. In addition, this test result is helpful in clarifying the risk for other
family members to develop cancer.
Probability (%)
If you have never had a cancer diagnosis, this test result means that the
chance for you to develop certain cancers is increased.
Lifetime Cancer Risks Associated
with BRCA1 Mutations
57-84%
60
24-54%
40
16-20%
20
4%
3%
0
Female
Breast
Male
Breast
Ovarian
Pancreatic
Prostate
Cancer Type
Management Options to Reduce Your Risk of Cancer:
Women who are positive for a BRCA1 mutation have a number of options available to them to reduce the risk of developing cancer. It is important for
you to discuss your cancer risks and your options for cancer surveillance and risk reduction in detail with your physician and/or genetic counselor. The
National Comprehensive Cancer Network (NCCN) recommends the following medical management options for women with a BRCA1 mutation:
Increased screening
• A breast MRI and mammogram every year beginning around age 25 can help in detecting cancer. Some studies have shown that alternating between a
mammogram and breast MRI every 6 months is effective in detecting cancer earlier.
• A clinical breast exam should be performed by a doctor every 6-12 months, starting at age 25.
• At age 18, it is important to become familiar with your breast tissue so that you may detect any changes that develop. Monthly self breast exams may help
you to notice such changes.
• Transvaginal ultrasound screening of the ovaries and a CA-125 blood test can be performed every 6 months, beginning around age 30, until you are ready to
consider surgical options.
• Men with a BRCA1 mutation are recommended to perform regular self breast exams and have clinical breast exams by a physician every 6-12 months
beginning at age 35. Baseline mammogram at age 40 can be considered. Annual mammograms may be recommended based on the baseline study. Early
prostate screening with a rectal exam of the prostate and a PSA blood test may also be a consideration for men with a BRCA1 mutation, starting at age 40.
It will take approximately three weeks to
complete the test (from the time testing
is started to the time your healthcare
provider receives the results). Your
healthcare provider or genetic counselor
will share the results with you and discuss
them in the context of your medical and
family histories. Each report is sent with
a patient-friendly report to better help
you understand your result.
Genetic Counseling
Pre-test genetic counseling is recommended for individuals who are
interested in understanding their risks, meet the clinical criteria for
testing, and/or are considering genetic testing. If a pathogenic variant
has already been identified in a family member, testing of the specific
variant is appropriate. If a pathogenic variant has never been identified,
an affected family member with the highest likelihood for a positive
result (e.g., with early-onset disease, bilateral disease or multiple
primaries) is ideally the best person for initial testing within a family.
If an affected family member is not available for testing, testing of an
unaffected family member can be performed, although a negative test
result will not guarantee that the individual does not have an increased
cancer risk. Once an individual decides to undergo testing, post-test
genetic counseling is recommended to understand the implications
GUIDE FOR HEREDITARY CANCERS: COMPREHENSIVE PANEL
7
of the results. Genetic counseling services across the country can be
found at: www.nsgc.org
Management
Various screening and surgical options are available to individuals who
test positive for pathogenic variants included on the Comprehensive
Cancer Panel, as discussed in Table 3.The guidelines below are
examples of current National Comprehensive Cancer Network
recommendations as of 2015 8,9,10. Other management options may
be considered, based upon personal and/or family histories. For
comprehensive gene-specific guidelines, including ages to begin
surveillance and current recommended screening frequencies, please
visit: www.nccn.com
Gene
Management Guidelines
BRCA1/
BRCA2
•
•
•
•
•
•
•
•
EPCAM,
MLH1,
MSH2,
MSH6,
PMS2
•F
requent colonoscopy (every 1-2 years in many cases) starting at an
early age
•C
onsider endometrial/ovarian cancer screening, which may include
endometrial biopsy, transvaginal ultrasound and CA-125 blood tests
•C
onsider prophylactic hysterectomy and salpingo-oophorectomy once
a woman has completed childbearing
• Consider
routine esophagogastroduodenoscopy (EGD) with extended
duodenoscopy starting at an early age
• Consider routine urinalysis starting at an early age
• Annual physical exam
•C
onsider the option of prophylactic colectomy, particularly if the
patient requires surgery to address a colonic neoplasm not amenable
to endoscopic resection
8
Increased breast awareness including breast self-exam
Routine clinical breast exams
Annual breast MRI and mammography starting at an early age
Consider transvaginal ultrasound of ovaries and CA-125 blood tests
Consider full body skin examination
Consider pancreatic cancer screening
Consider routine prostate cancer screening starting at an early age
C
onsider the use of risk-reducing medications (such as tamoxifen,
raloxifene and oral contraceptives)
• Consider prophylactic mastectomy
•S
alpingo-oopherectomy is recommended (as early as the 30s-40s)
once a woman has completed childbearing
Gene
Management Guidelines
APC
•F
requent colonoscopy starting at an early age; if adenomas are
identified, increase the interval of colonoscopy
• If the patient undergoes colectomy, continued routine endoscopic
evaluation post-colectomy
• Routine esophagogastroduodenoscopy (EGD) starting at an early age
• Routine thyroid exam
• Annual physical exam
•P
rophylactic colectomy is not always needed in AFAP. Colectomy
is generally recommended for individuals who have adenomas that
cannot be managed through colonoscopy.
MUTYH
• Annual physical exam
• Frequent colonoscopy starting at an early age
•C
onsider routine esophagogastroduodenoscopy (EGD) and sideviewing duodenoscopy starting at an early age
SMAD4/
BMPR1A
• Frequent colonoscopy starting at an early age
• Routine upper endoscopy starting at an early age
•F
or SMAD4 pathogenic variant carriers, screen for vascular lesions
associated with hereditary hemorrhagic telangiectasia
CDH1
•
•
•
•
•
•
CDKN2A
• Routine total body dermatological exams starting at an early age
• Routine skin self-exams
•C
onsider pancreatic cancer screening (e.g. magnetic resonance
cholangiopancreatography (MRCP), endoscopic ultrasound, etc.)
either clinically or through clinical research programs
ATM
• Increased breast awareness including breast self-exam
• Routine clinical breast exam
• Annual breast MRI and mammogram
CHEK2
• Increased breast awareness including breast self-exam
• Routine clinical breast exam
• Annual breast MRI and mammogram starting at an early age
PALB2
• Increased breast awareness including breast self-exam
• Routine clinical breast exam
• Annual breast MRI and mammogram
(biallelic
pathogenic
variants)
Increased breast awareness including breast self-exam
Routine clinical breast exam
Routine breast MRI and mammography
Routine endoscopy starting at an early age
Strong consideration of prophylactic gastrectomy
C
onsider the use of breast cancer chemoprevention and/or
prophylactic mastectomy
• Routine colonoscopy
GUIDE FOR HEREDITARY CANCERS: COMPREHENSIVE PANEL
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Gene
Management Guidelines
PTEN
•
•
•
•
•
•
•
•
•
•
STK11
•
•
•
•
•
•
TP53
•
•
•
•
•
•
•
•
•
•
•
•
VHL
•
•
•
•
•
•
Increased breast awareness including breast self-exam
R
outine clinical breast exam
B
reast MRI and mammography starting at an early age
C
onsider endometrial biopsy and/or transvaginal ultrasound starting at
an early age; encourage patient education and prompt response
to symptoms
Options of prophylactic mastectomy and hysterectomy can be discussed
Annual physical exam
R
outine colonoscopy
Consider routine dermatologic exam
A
nnual thyroid ultrasound
Consider routine renal ultrasounds starting at an early age
Increased breast awareness including breast self-exam
Routine clinical breast exam
Routine breast MRI and mammography starting at an early age
Frequent colonoscopy starting at an early age
Routine upper endoscopy starting at an early age
Routine pancreatic cancer screening (e.g., magnetic resonance
cholangiopancreatography (MRCP) or endoscopic ultrasound) starting
at an early age
• Routine small bowel visualization starting at an early age
• Routine pelvic exam with consideration of transvaginal ultrasound
• Annual physical exam
Increased breast awareness including breast self-exam
Routine clinical breast exam
Breast MRI and mammography starting at an early age
Consider prophylactic mastectomy
Consider increased colonoscopy screening starting at an early age
Comprehensive physical exam including neurologic exam
Use caution regarding radiation therapy for cancer
Consider routine whole body MRI
Full body skin exam
Whole body MRI
Brain imaging as part of whole body MRI or as separate exam
Additional surveillance based on family history of cancer
Annual physical exams
Routine blood pressure monitoring
Routine MRI of brain/spine
Routine ophthalmology exams
Routine formal hearing evaluations
R
outine urine/blood fractionated metanephrines to screen for
pheochromocytoma
•R
outine imaging (e.g., abdominal ultrasounds, MRIs) to evaluate the
kidneys, adrenal glands, and pancreas
• Pregnant women affected with VHL require additional monitoring
Table 3: Management Guidelines for Pathogenic Variant Carriers
10
If results are positive for a pathogenic variant,
can GeneDx test family members for the same
variant?
Yes, GeneDx offers family members targeted testing of previously
identified pathogenic variants. This testing must be ordered by a doctor.
Sharing a copy of the genetic test report can help a family member’s
doctor order the correct genetic testing.
If a family member has been tested at another lab and was found
to have a pathogenic variant, we can still test an individual for that
variant. We require at least a copy of the report from the laboratory that
previously performed the testing on the family member, and we also
prefer a blood or oral rinse (mouthwash) sample from the previouslytested relative to be sent along with the sample for confirmation. For
more information, please call one of our genetic counselors at:
888-729-1206.
Will insurance cover this test?
We accept all commercial insurance, Medicare, and certain state
Medicaid plans. Many insurance companies, including Medicare and
Medicaid, have specific criteria and prior-authorization requirements
for genetic testing as a covered benefit. GeneDx will bill the insurance
company and appeal for payment. Additionally, for insurance other
than Medicare, our billing department will contact the insured individual
if there are out-of-pocket expenses over $100. For more information,
please visit our website at: www.oncogenedx.com or call us at:
888-729-1206.
Can testing be done without insurance?
If an individual does not have health insurance or cannot afford to pay
the full cost of testing, GeneDx provides a financial assistance program.
For more information, call us at: 888-729-1206.
GUIDE FOR HEREDITARY CANCERS: COMPREHENSIVE PANEL
11
Can health insurers or employers discriminate
against an individual based on test results?
The Genetic Information Nondiscrimination Act of 2008, also
referred to as GINA, is a federal law that protects most Americans
from discrimination by health insurance companies and employers
based on their genetic information. For more information, please
visit: http://genome.gov/10002328
Patient Resources
For more information and educational videos about the Comprehensive
Cancer Panel, please visit: www.oncogenedx.com/patient
Bright Pink: www.brightpink.org
C3: Colorectal Cancer Coalition: www.fightcolorectalcancer.org
Colon Cancer Alliance: www.ccalliance.org
FORCE: www.facingourrisk.org
Hereditary Colon Cancer Takes Guts: www.hcctakesguts.org
Sharsheret: www.sharsheret.org
Susan G. Komen: www.komen.org
National Cancer Institute: www.cancer.gov/cancertopics/genetics
National Society of Genetic Counselors: www.nsgc.org
References:
1. Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. SEER
Cancer Statistics Review, 1975-2009: Lifetime Risk Tables (URL: http://surveillance.cancer.gov/devcan)
[May 2013 accessed].
2. Berliner JL, Fay AM. Risk assessment and genetic counseling for hereditary breast and ovarian cancer:
Recommendations of the National Society of Genetic Counselors. J Genet Couns 16(3):241, 2007.
3. Walsh T, Casadei S, Lee MK, et al. Mutations in 12 genes for inherited ovarian cancer, fallopian tube,and
peritoneal carcinoma identified by massively parallel sequencing. PNAS 2011;108:18032, 2011.
4. Lynch HT, Smyrk T, Kern SE, et al. Familial pancreatic cancer: a review. SeminOncol 23:251, 1996.
5. Brand RE, Lynch HT. Hereditary pancreatic adenocarcinoma. A clinical perspective. Med Clin North Am
84:665, 2000.
6. Grover S, Syngal S. Hereditary pancreatic cancer. Gastroenterol 139:1076, 2010.
7. Hampel, et al. Comment on: Screening for Lynch Syndrome (hereditary nonpolyposis colorectal cancer)
among endometrial cancer patients. Cancer Res. 2007;67:9603
8. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Genetic/Familial High-Risk
Assessment: Breast and Ovarian. Version 2.2015.
9. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Genetic/Familial High-Risk
Assessment: Colorectal. Version 1.2015.
10.NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Gastric Cancer. Version 3.2015.
12
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