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Developed in collaboration with Fox Chase Cancer Center and the Arcadia University Genetic Counseling Program.
BRCAplus
genetic testing for hereditary breast cancer
Causes of Hereditary Breast Cancer
familial 15-20%
hereditary 5-10%
unknown
brc a1 & brc a 2 (up to 50%)
additional genes in brc aplus & bre a stne x t (12-30%)
spor adic70-80%
Lifetime Breast Cancer Risks
* Specific level of risk depends on the family history of breast cancer
** Specific level of risk depends on the gene involved
up to 87%**
Average
-12%
Moderate Risk Genes
-20 to 58%**
Familial High Risk Genes
>12%*
Signs of Hereditary Breast and Ovarian Cancer
o Early-onset breast cancer (diagnosed < 45 years of age)
o Bilateral or multiple primary breast cancers
o Male breast cancer at any age
o Breast and ovarian cancer in the same woman
o Family with 3 or more cases of breast cancer*
o Triple negative breast cancer <60y
o 3 or more cases of breast, ovarian, and/or pancreatic cancer*
o 3 or more cases of breast, uterine and/or thyroid cancer*
o Multiple close family member with breast and other cancers*
* On the same side of the family
BRCAplus Genes and Associated Cancers
gene(s) syndrome associated cancers
ATM Breast, pancreatic, prostate
BRCA1/BRCA2
Hereditary Breast and Ovarian Cancer (HBOC) Breast, ovarian, pancreatic, prostate, melanoma
CDH1 Hereditary Diffuse Gastric Cancer Diffuse gastric cancer, lobular breast cancer
CHEK2 Breast, colorectal, prostate, other
PALB2 Breast, pancreatic, male breast cancer
PTEN Cowden syndrome Breast, thyroid, uterine, colorectal, kidney
TP53 Li-Fraumeni syndrome (LFS) Breast, sarcoma, brain, adrenocortical carcinoma, leukemia, other
Lifetime Breast Cancer Risks By BRCAplus Gene (%)
* Breast cancer is the most common cancer in women with TP53 mutations. Although the breast cancer risk with a TP53 mutation is significantly elevated above the general population, the specific risk is not well defined.
BRCA1, BRCA2
up to 50PTEN
33-58
Significantly Increased*
PALB2
TP53
General Population 12
45-87
39-52CDH1
BRCAplus Gene Mutation
ATM
CHEK2
2-4 fold
2 fold
What Do My Test Results Mean?
Pathogenic Mutation
Positive
Medical management based on cancer risks
specific to gene mutationVariant,
Likely Pathogenic
Variant, Unknown Significance (VUS) Unknown
Variant, Likely BenignNegative
Medical management based on personal
and/or family history of cancer
No Variants Detected
genetic test results meaning implications
Positive Test Results
A mutation was found
Recommendations based on genetic test result
Increased risk for certain types of cancer
Recommend genetic counseling and considerationof genetic testing
Result
Cancer Screening and Prevention
Cancer Risks
Genetic Testing For Family Members
Negative Test Results
Result
Cancer Screening and Prevention
Cancer Risks
Genetic Testing For Family Members
No mutations were found
Recommendations based on personal and/or family history
Based on personal and/or family history
Usually not recommended
Variant of Unknown Significance Test Results
Result
Cancer Screening and Prevention
Cancer Risks
Genetic Testing For Family Members
A genetic change was found, but it is unclear if it causes increased risk for cancer
Recommendations based on personal and/or family history
Based on personal and/or family history
Usually not recommended
BreastNext
genetic testing for hereditary breast cancer
Causes of Hereditary Breast Cancer
BRCA1, BRCA2
TP53, PTEN, CDH1
ATM, CHEK2, PALB2
RAD50, RAD51C, RAD51D, BARD1, BRIP1, MRE11A, NBN, MUTYH, NF1
Other genes
familial 15-20%
hereditary 5-10%
spor adic70-80%
Lifetime Breast Cancer Risks
* Specific level of risk depends on the family history of breast cancer
** Specific level of risk depends on the gene involved
up to 87%**
Average
-12%
Moderate Risk Genes
-20 to 58%**
Familial High Risk Genes
>12%*
Signs of Hereditary Breast and Ovarian Cancer
o Early-onset breast cancer (diagnosed < 45 years of age)
o Bilateral or multiple primary breast cancers
o Male breast cancer at any age
o Breast and ovarian cancer in the same women
o Family with 3 or more cases of breast cancer*
o Triple negative breast cancer < age 60
o 3 or more cases of breast, ovarian, and/or pancreatic cancer*
o 3 or more cases of breast, uterine and/or thyroid cancer*
o Multiple close family member with breast and other cancers*
*On the same side of the family
BreastNext Genes and Implications
HIGH RISK GENES
MODERATE RISK GENES
ELEVATED RISK GENES
Genes BRCA1, BRCA2, CDH1, PTEN, TP53
ATM, CHEK2, PALB2, NF1 BARD1, BRIP1, MRE11A, MUTYH, NBN, RAD50, RAD51C, RAD51D
Lifetime Breast Cancer Risk
45-87% 20-58% Increased, but not well defined
Medical Management
• Established guidelines for screening and prevention
• Established guidelines for screening and prevention
• Screening and/or prevention guidelines may or may not be established
• Management based on family history and estimated cancer risk
Breast Cancer Risk Management
HIGH RISK MODERATE RISK AVERAGE RISK
Breast Screening • Annual MRI starting at age 25• Add annual mammogram
at age 30• Clinical breast exam every 6-12
months
• Mammogram may begin younger than age 40
• Additional imaging, such as breast MRI, may be recommended
• Clinical breast exam every 6-12 months
• Annual mammogram starting age 40
• Annual clinical breast exam
Risk-Reducing Surgery
Risk reducing mastectomy is an option
Risk reducing mastectomy may be an option
Not recommended
Risk-Reducing Medications
Tamoxifen may be an option Tamoxifen may be an option Not recommended
Genes and Associated Cancersgenes breast ovarian colorectal uterine pancreatic others
ATM ü ü
BRCA1 ü ü ü ü
BRCA2 ü ü ü ü
CDH1 ü ü ü
CHEK2 ü ü
PALB2 ü ü
PTEN ü ü ü ü
TP53 ü ü ü ü ü ü
BARD1 ü ü
BRIP1 ü ü
MRE11A ü ü
MUTYH ü ü
NBN ü ü
NF1 ü ü
RAD50 ü ü
RAD51C ü ü
RAD51D ü ü
BRCA
plus
Brea
stN
ext
What Do My Test Results Mean?
Pathogenic Mutation
Positive
Medical management based on cancer risks
specific to gene mutationVariant,
Likely Pathogenic
Variant, Unknown Significance (VUS) Unknown
Variant, Likely BenignNegative
Medical management based on personal
and/or family history of cancer
No Variants Detected
genetic test results meaning implications
Positive Test Results (high risk gene)
Result
Cancer Screening and Prevention
Cancer Risks
Genetic Testing For Family Members
A mutation was found
Recommendations based on genetic test result
Increased risk for certain types of cancer
Recommend genetic counseling and considerationof genetic testing
Positive Test Results (moderate risk gene)
Result
Cancer Screening and Prevention
Cancer Risks
Genetic Testing For Family Members
A mutation was found
Recommendations based on genetic test result and family history
Moderately increased risk for certain types of cancer
Recommend genetic counseling and consideration of genetic testing
Negative Test Results
Recommendations based on personal and/or family history
Based on personal and/or family history
No mutations were found
Usually not recommended
Result
Cancer Screening and Prevention
Cancer Risks
Genetic Testing For Family Members
Variant of Unknown Significance Test Results
A genetic change was found, but it is unclear if it causes increased risk for cancer
Recommendations based on personal and/or family history
Based on personal and/or family history
Usually not recommended
Result
Cancer Screening and Prevention
Cancer Risks
Genetic Testing For Family Members
50339.3316_v5 | 11.22.17