genetic testing for hereditary breast cancer · lifetime breast cancer risks by brcaplus gene (%) *...

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 Risks


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 Risks


A genetic change was found, but it is unclear if it causes increased risk for cancer




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 Risks



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 Risks



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



No mutations were found


Result


Cancer Risks


Variant of Unknown Significance Test Results

A genetic change was found, but it is unclear if it causes increased risk for cancer




Result


Cancer Risks


50339.3316_v5 | 11.22.17

genetic testing for hereditary breast cancer · lifetime breast cancer risks by brcaplus gene (%) *...

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