BRCAplus. genetic testing for hereditary breast cancer
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1 BRCAplus genetic testing for hereditary breast cancer Developed in collaboration with Fox Chase Cancer Center and the Arcadia University Genetic Counseling Program.
2 Causes of Hereditary Breast Cancer familial 15-20% hereditary 5-10% brca1 & brca2 (up to 50%) additional genes in brcaplus & breastnext (12-30%) sporadic 70-80% unknown
3 Lifetime Breast Cancer Risks up to 87%** -20 to 58%** >12%* -12% Average Familial Moderate Risk Genes High Risk Genes * Specific level of risk depends on the family history of breast cancer ** Specific level of risk depends on the gene involved
4 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
5 BRCAplus Genes and Associated Cancers gene(s) syndrome associated cancers ATM BRCA1/ BRCA2 Hereditary Breast and Ovarian Cancer (HBOC) Breast, pancreatic, prostate Breast, ovarian, pancreatic, prostate, melanoma CDH1 Hereditary Diffuse Gastric Cancer Diffuse gastric cancer, lobular breast cancer CHEK2 PALB2 Breast, colorectal, prostate, other 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
6 Lifetime Breast Cancer Risks By BRCAplus Gene (%) General Population 12 BRCAplus Gene Mutation ATM 2-4 fold BRCA1, BRCA CDH CHEK2 2 fold PTEN up to 50 PALB2 TP Significantly Increased* * 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.
7 What Do My Test Results Mean? genetic test results meaning implications Pathogenic Mutation Variant, Likely Pathogenic Variant, Unknown Significance (VUS) Variant, Likely Benign No Variants Detected Positive Unknown Negative Medical management based on cancer risks specific to gene mutation Medical management based on personal and/or family history of cancer
8 Positive Test Results Result A mutation was found Cancer Risks Increased risk for certain types of cancer Cancer Screening and Prevention Recommendations based on genetic test result Genetic Testing For Family Members Recommend genetic counseling and consideration of genetic testing
9 Negative Test Results Result No mutations were found Cancer Risks Based on personal and/or family history Cancer Screening and Prevention Recommendations based on personal and/or family history Genetic Testing For Family Members Usually not recommended
10 Variant of Unknown Significance Test Results Result A genetic change was found, but it is unclear if it causes increased risk for cancer Cancer Risks Based on personal and/or family history Cancer Screening and Prevention Recommendations based on personal and/or family history Genetic Testing For Family Members Usually not recommended
11 BreastNext genetic testing for hereditary breast cancer
12 Causes of Hereditary Breast Cancer sporadic 70-80% familial 15-20% hereditary 5-10% BRCA1, BRCA2 TP53, PTEN, CDH1 ATM, CHEK2, PALB2 RAD50, RAD51C, RAD51D, BARD1, BRIP1, MRE11A, NBN, MUTYH, NF1 Other genes
13 Lifetime Breast Cancer Risks up to 87%** -20 to 58%** >12%* -12% Average Familial Moderate Risk Genes High Risk Genes * Specific level of risk depends on the family history of breast cancer ** Specific level of risk depends on the gene involved
14 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
15 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
16 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
17 Genes and Associated Cancers BreastNext BRCAplus genes 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
18 What Do My Test Results Mean? genetic test results meaning implications Pathogenic Mutation Variant, Likely Pathogenic Variant, Unknown Significance (VUS) Variant, Likely Benign No Variants Detected Positive Unknown Negative Medical management based on cancer risks specific to gene mutation Medical management based on personal and/or family history of cancer
19 Positive Test Results (high risk gene) Result A mutation was found Cancer Risks Increased risk for certain types of cancer Cancer Screening and Prevention Recommendations based on genetic test result Genetic Testing For Family Members Recommend genetic counseling and consideration of genetic testing
20 Positive Test Results (moderate risk gene) Result A mutation was found Cancer Risks Moderately increased risk for certain types of cancer Cancer Screening and Prevention Recommendations based on genetic test result and family history Genetic Testing For Family Members Recommend genetic counseling and consideration of genetic testing
21 Negative Test Results Result No mutations were found Cancer Risks Based on personal and/or family history Cancer Screening and Prevention Recommendations based on personal and/or family history Genetic Testing For Family Members Usually not recommended
22 Variant of Unknown Significance Test Results Result A genetic change was found, but it is unclear if it causes increased risk for cancer Cancer Risks Based on personal and/or family history Cancer Screening and Prevention Recommendations based on personal and/or family history Genetic Testing For Family Members Usually not recommended
23 _v
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