hereditary breast cancer

Most cases of breast cancer are sporadic; the cause is unknown. However, there is a subset of breast cancer that is caused by a genetic mutation passed from parent to child. This is called hereditary breast cancer. Women who have a deleterious mutation in a gene known to significantly increase the risk of breast cancer are candidates for a risk reducing mastectomy.


 
jolie.time.jpg

Angelina jolie

Academy Award winning actor, filmmaker, and humanitarian, is also a carrier of a deleterious mutation in the BRCA1 gene. In May 2013, she shared her very personal story about risk reducing bilateral mastectomy and reconstruction, in an effort to raise awareness. *photo by Melodie McDaniel/Trunk Archive


Genes associated with breast cancer

 

Below are the genes most commonly associated with Hereditary Breast Cancer. This list is not complete. Some of these genes were recently identified and therefore, our understanding of their risk is limited. Furthermore, science has yet to discover all of the genes that are linked to breast cancer risk. 


brca1

Women with a deleterious mutation in the BRCA1 gene have a condition referred to as hereditary breast and ovarian cancer syndrome (HBOC). This is the single highest risk for breast cancer. These women have up to an 87% lifetime risk of breast cancer. These women also have a 20% risk of getting a second breast cancer within 5 years from their first diagnosis. Women with a BRCA1 mutation should start breast cancer screening at least by age 25. This will include annual mammogram and MRI. These women can also consider taking a hormone blocking medication (e.g. Tamoxifen) to decrease their risk, although this recommendation is controversial. Women with a BRCA1 mutation often choose risk-reducing (prophylactic) mastectomy with reconstruction. It is also recommended that these women have risk-reducing oophorectomy (i.e. removal of ovarian tissue, including fallopian tubes) by age 35-40, depending on family planning. This is due to the high risk of ovarian cancer associated with a BRCA mutation. There is not yet a reliable screening protocol for ovarian cancer. However most women are screened with an annual trans-vaginal pelvic ultrasound, a blood test to check the serum level of ca-125, and a clinical exam. It is also a good idea for women with a BRCA mutation to consider oral contraceptives to decrease the risk of ovarian cancer. 


brca2

Women with a deleterious mutation in the BRCA2 gene also have a condition referred to as hereditary breast and ovarian cancer syndrome (HBOC). This is the second highest risk for breast cancer. These women have up to an 84% lifetime risk of breast cancer. These women also have a 12% risk of getting a second breast cancer within 5 years from their first diagnosis. Women with a BRCA2 mutation should start breast cancer screening at least by age 25. This will include annual mammogram and MRI. These women can also consider taking a hormone blocking medication (e.g. Tamoxifen) to decrease their risk, although this recommendation is controversial. Women with a BRCA1 mutation often choose risk-reducing (prophylactic) mastectomy with reconstruction. It is also recommended that these women have risk-reducing oophorectomy (removal of ovarian tissue, including fallopian tubes) by age 35-40, depending on family planning. This is due to the high risk of ovarian cancer associated with a BRCA mutation. There is not yet a reliable screening protocol for ovarian cancer. However most women are screened with an annual trans-vaginal pelvic ultrasound, a blood test to check the serum level of ca-125, and a clinical exam. It is also a good idea for women with a BRCA mutation to consider oral contraceptives to decrease the risk of ovarian cancer. 


palb2

Women with a deleterious PALB2 mutation have an elevated risk for breast cancer. This can be up to a 58% risk for developing breast cancer by age 70.  Estimates of this risk vary and are influenced by family history.  PALB2 mutations also increase the risk of pancreatic cancer, although the exact risk is unknown. PALB2 mutations are also associated with male breast cancer. The general recommendation is for these women to start breast cancer screening by age 30. If there is a history of breast cancer affecting family members at an age <40, the recommendation is to consider screening 10 years earlier than the age at which the youngest family member was diagnosed with breast cancer.  Women with a PALB2 mutation should be screened with an annual mammogram, MRI, and a clinical breast exam.  These women may also elect to have risk-reducing mastectomy with reconstruction. 


chek2

Women with a deleterious CHEK2 mutation have a significantly higher than average risk for breast cancer. It is estimated that their lifetime risk may be as high as 48%. These women also have an increased chance of developing a second breast cancer. This risk can be up to 29% within the first 10 years from the time of their original diagnosis. This is very significant when you consider the fact that the average woman has a 12% lifetime risk of developing breast cancer.  Men with CHEK2 mutations also have an increased risk for breast cancer.  It is recommended that women with a CHEK2 mutation should start screening by age 40, or earlier, depending on the family history of breast cancer. These women should be screened with an annual mammogram, MRI, and a clinical breast exam.  These women may be candidates for risk-reducing mastectomy with reconstruction. 


ATM

A deleterious mutation of the ATM gene significantly increases a woman's risk of developing breast cancer. This risk may be skewed towards affecting women at younger ages. The lifetime risk of developing breast cancer for women with ATM mutations may be as high as 52%. There is also an increased risk for pancreatic cancer for mutation carriers who have a family history of pancreatic cancer in 2 or more close relatives. Women should start screening for breast cancer by age 40, or earlier if there is a family history of breast cancer at young ages.  Screening should included a mammogram, MRI, and a clinical breast exam annually . These women may choose to have risk-reducing mastectomy with reconstruction.  


nbn

NBN mutations are most common in patients of Slavic ancestry. Current female breast cancer and male prostate cancer risk estimates are based primarily on studies of individuals of Eastern European ancestry with this specific mutation, and may not apply to other NBN mutations or patients of other ancestries. Women may have an elevated risk of breast cancer up to 30%. They will also have an increased risk for pancreatic cancer. Women should begin screening at age 40. This should include an annual mammogram and clinical breast exam. An annual screening MRI is often added for these women based on the recommendation by the American Cancer Society; women with a lifetime risk estimated to be 20% or higher should consider MRI in addition to mammogram for screening. 


tp53

A germline mutation in the TP53 gene causes a medical condition called Li-Fraumeni Syndrome(LFS). A germline mutation is a mutation that is present in all cells of the body.  Women with LFS have an elevated risk for many types of cancer. These cancers typically occur at ages < 45. One of the most common cancers associated with LFS is premenopausal breast cancer. LFS is a very rare condition that should be managed by a physician with experience taking care of this syndrome due to its complexity.  Screening for breast cancer should begin at age 20 (or earlier if the youngest affected family member was diagnosed with breast cancer before age 20) and should include an MRI and clinical breast exam. Mammogram should be added to MRI and clinical exam by age 30. These women are also offered the option of risk-reducing mastectomy with reconstruction.


bard1

BARD1 mutations have been found in families suspected of having a form of hereditary breast and ovarian cancer syndrome (HBOC), but without detectable mutations in BRCA1 or BRCA2. The exact risk of breast cancer associated with BARD1 mutations is unknown.  Screening recommendations should be based on the individual's family history of breast cancer. In is reasonable to consider enhanced screening, such as annual MRI, in addition to mammogram


stk11

Mutations in the STK11 gene cause a condition called Peutz-Jeghers syndrome (PJS). Women with PJS have a risk for breast cancer that is significantly increased over the 12.5% lifetime risk for women in the general population. PJS also increases the risk for a variety of other cancers, including colorectal, endometrial, gastric, pancreatic, small bowel, cervical and lung cancers. These cancers often occur at young ages. The risk for breast cancer is estimated to be up to 50% lifetime risk. These women should start screening with clinical exam, mammogram, and MRI at age 25.  These women might consider risk-reducing mastectomy with recontruction. 


pten

A deleterious mutation in the gene PTEN causes a condition called PTEN hamartoma tumor syndrome(PHTS). Women with PHTS have a significantly increased risk for breast cancer. This risk may be as high as 85%. Individuals will also have an increased risk for colorectal cancer, endometrial cancer, thyroid cancer, renal (kidney) cancer, and melanoma. The diagnosis is often cancer occurs at relatively young ages. Breast cancer screening recommendations should include clinical breast exam starting at age 25 and imaging starting at age 30.  If there is a family history of breast cancer at ages younger than 25, screening should begin earlier. Imaging should include both mammogram and MRI. These women are also candidates for risk-reducing mastectomy with reconstruction. 


cdh1

A mutation in the CDH1 gene leads to a condition called hereditary diffuse gastric cancer syndrome (HDGC).  The majority of gastric (stomach) cancers in these people will be diagnosed before age 40. Women with this mutation have an increased risk for lobular breast cancer. This may be up to a 52% lifetime risk. Women should have clinical breast exams starting at age 25. Mammogram and MRI should begin by age 30. These women may consider taking Tamoxifen for risk reduction. Mastectomy with reconstruction is also an option for reducing risk.