BRCA1 and BRCA2 Gene Mutations

Hereditary Breast and Ovarian Cancer syndrome (HBOC)

BRCA1 and BRCA2 Associated Cancer Risks
BREAST OVARIAN GASTRIC COLORECTAL PANCREATIC MELANOMA PROSTATE ENDOMETRIAL OTHER

What does it mean to have a BRCA1 or BRCA2 gene mutation, and a diagnosis of Hereditary Breast and Ovarian Cancer syndrome (HBOC)?

Hereditary Breast and Ovarian Cancer syndrome (HBOC) is caused by mutations in one of two genes: BRCA1 or BRCA2. Women with HBOC have a high risk for both breast and ovarian cancer. Men with HBOC have an increased risk for breast cancer and prostate cancer. Both men and women with HBOC may have an increased risk for melanoma and pancreatic cancer. Sometimes, these cancers can develop at young ages.

The exact cancer risks and medical management guidelines for people with HBOC differ slightly depending on whether HBOC is caused by a BRCA1 or a BRCA2 gene mutation.


What can be done to protect people with HBOC from cancer?

The National Comprehensive Cancer Network (NCCN) provides recommendations for lowering the risk of cancer in men and women with HBOC. These recommendations include special screening for the cancers with high risks. This can mean starting screening at younger ages than typically recommended, performing the screenings more often and using more sensitive technologies. For example, women with HBOC should begin breast screening in their 20’s, and they should have MRIs in addition to, or instead of, mammograms. The risk of breast cancer in women with HBOC is very high, and in some cases it may even be reasonable to consider surgery to remove the breasts before cancer can develop.

It is difficult to screen for ovarian cancer, and women with HBOC have a high risk of developing this cancer. Therefore, NCCN recommends that women with HBOC have surgery to remove their ovaries and fallopian tubes between 35 and 40 years, or after they have finished having children.

Men with HBOC should begin breast screening exams done by their doctors beginning in their 30’s. In some cases, mammograms may also be recommended. Men should talk to their doctors and other healthcare providers about screening for prostate cancer.

Screening for pancreatic cancer is more likely to be recommended for men and women who have HBOC and have a history of pancreatic cancer in their family. Currently, pancreatic cancer screening is mostly performed in research settings.

Additional details about BRCA1 and BRCA2 gene mutations and HBOC, including information about the risks for different kinds of cancer, specific recommendations for medical care, and useful information for relatives of people who have a diagnosis of HBOC, are available within our Support Organizations pages.

BRCA1 gene

Associated Syndrome Name: Hereditary Breast and Ovarian Cancer syndrome (HBOC)

BRCA1 Summary Cancer Risk Table

Cancer Genetic Cancer Risk
Female BreastHigh Risk
OvarianHigh Risk
Male BreastElevated Risk
PancreaticElevated Risk
ProstateElevated Risk

BRCA1 gene Overview

Hereditary Breast and Ovarian Cancer syndrome (HBOC) 1
  • Individuals with mutations in BRCA1 have a condition called Hereditary Breast and Ovarian Cancer syndrome (HBOC).
  • Women with HBOC have a risk for breast cancer that is greatly increased over the 12.5% lifetime risk for women in the general population of the United States.
  • Women with HBOC also have high risks for ovarian, fallopian tube, and primary peritoneal cancer.
  • Men with HBOC due to mutations in BRCA1 have an elevated risk for breast and prostate cancer. The increased risk for prostate cancer may be most significant at younger ages.
  • Male and female patients with HBOC due to mutations in BRCA1 have an elevated risk for pancreatic cancer.
  • Although there are high cancer risks for patients with HBOC, there are interventions that have been shown to be effective at reducing many of these risks. Guidelines from the National Comprehensive Cancer Network (NCCN) for the medical management of patients with HBOC are listed below. It is recommended that patients with BRCA1 mutations and a diagnosis of HBOC be managed by a multidisciplinary team with experience in the prevention and treatment of the cancers associated with HBOC.

BRCA1 gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population *
Female BreastTo age 503, 4, 528%-51%1.9%
To age 704, 5, 646%-87%7.3%
Second primary within 5 years of first breast cancer diagnosis720%2%
OvarianTo age 503, 413%-23%0.2%
To age 703, 4, 539%-63%0.7%
Ovarian cancer within 10 years of a breast cancer diagnosis812.7%<1.0%
ProstateTo age 709, 10Up to 16%8.2%
Male BreastTo age 70111.2%<0.1%
PancreaticTo age 8012Elevated risk1%

BRCA1 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines as of the last Myriad update shown on this page. The specific reference provided (e.g., NCCN guidelines) should be consulted for more details and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

Cancer Type Procedure Age to Begin Frequency
Female BreastBreast awareness - Women should be familiar with their breasts and promptly report changes to their healthcare provider. Periodic, consistent breast self-examination (BSE) may facilitate breast awareness.118 yearsNA
Clinical breast examination125 yearsEvery 6 to 12 months
Breast MRI with contrast and/or Mammography1Age 25 for MRI (preferred) or mammography. Age 30 for both MRI and mammography. Individualize to a younger age if a relative has been diagnosed younger than age 30.Annually
Consider investigational screening studies within clinical trials.1IndividualizedNA
Consider risk-reducing mastectomy.1IndividualizedNA
Consider options for breast cancer risk-reduction agents (i.e. tamoxifen).1IndividualizedNA
OvarianBilateral salpingo-oophorectomy135 to 40 years, upon completion of childbearingNA
Consider transvaginal ultrasound and CA-125 measurement. Consider investigational screening studies within clinical trials.130 to 35 yearsIndividualized
Consider options for ovarian cancer risk-reduction agents (i.e. oral contraceptives).1IndividualizedNA
ProstateConsider prostate cancer screening.145 yearsIndividualized
Male BreastBreast self-examination135 yearsMonthly
Clinical breast examination135 yearsAnnually
PancreaticCurrently there are no specific medical management guidelines for pancreatic cancer risk in mutation carriers.NANA

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the BRCA1 gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.

References

  1. Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast and Ovarian. V 1.2017. September 19. Available at http://www.nccn.org.
  2. Surveillance Research Program, National Cancer Institute SEER*Stat software (seer.cancer.gov/seerstat) V 8.0.1, Nov 19, 2012.
  3. Easton DF, et al. Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet. 1995 56:265-71. PMID: 7825587.
  4. Chen S, et al. Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol. 2006 24:863-71. PMID: 16484695.
  5. Mavaddat N, et al. Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. J Natl Cancer Inst. 2013 105:812-22. PMID: 23628597.
  6. Ford D, et al. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet. 1994 343:692-5. PMID: 7907678.
  7. Verhoog LC, et al. Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1. Lancet. 1998 351:316-21. PMID: 9652611.
  8. Metcalfe KA, et al. The risk of ovarian cancer after breast cancer in BRCA1 and BRCA2 carriers. Gynecol Oncol. 2005 96:222-6. PMID: 15589605.
  9. Struewing JP, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med. 1997 336:1401-8. PMID: 9145676.
  10. Liede A, et al. Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J Clin Oncol. 2004 22:735-42. PMID: 14966099.
  11. Tai YC, et al. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2007 99:1811-4. PMID: 18042939.
  12. Lynch HT, et al. BRCA1 and pancreatic cancer: pedigree findings and their causal relationships. Cancer Genet Cytogenet. 2005 158:119-25. PMID: 15796958.
Last Updated on 01-Jun-2017

BRCA2 gene

Associated Syndrome Name: Hereditary Breast and Ovarian Cancer syndrome (HBOC)

BRCA2 Summary Cancer Risk Table

Cancer Genetic Cancer Risk
Male BreastHigh Risk
Female BreastHigh Risk
PancreaticHigh Risk
OvarianHigh Risk
MelanomaElevated Risk
ProstateElevated Risk

BRCA2 gene Overview

Hereditary Breast and Ovarian Cancer syndrome (HBOC) 1
  • Individuals with mutations in BRCA2 have a condition called Hereditary Breast and Ovarian Cancer syndrome (HBOC).
  • Women with HBOC have a risk for breast cancer that is greatly increased over the 12.5% lifetime risk for women in the general population of the United States.
  • Women with HBOC also have high risks for ovarian, fallopian tube, and primary peritoneal cancer.
  • Men with HBOC due to mutations in BRCA2 have a high risk for breast cancer and an elevated risk for prostate cancer. The increase in prostate cancer risk is most significant at younger ages.
  • Male and female patients with HBOC due to a mutation in BRCA2 also have a high risk for pancreatic cancer and an elevated risk for melanomas of both the skin and eyes.
  • Although there are high cancer risks for patients with HBOC, there are interventions that have been shown to be effective at reducing many of these risks. Guidelines from the National Comprehensive Cancer Network (NCCN) for the medical management of patients with HBOC are listed below. It is recommended that patients with BRCA2 mutations and a diagnosis of HBOC be managed by a multidisciplinary team with experience in the prevention and treatment of the cancers associated with HBOC.

BRCA2 gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population *
Female BreastTo age 503, 423%-28%1.9%
To age 703, 4, 543%-84%7.3%
Second primary within 5 years of first breast cancer diagnosis612%2%
OvarianTo age 503, 4, 50.4%-4%0.2%
To age 703, 4, 516.5%-27%0.7%
Ovarian cancer within 10 years of a breast cancer diagnosis76.8%<1.0%
PancreaticTo age 808, 97%, or higher if there is a family history of pancreatic cancer.1%
Male BreastTo age 70106.8%<0.1%
ProstateTo age 701020%8.2%
MelanomaTo age 8011, 12Elevated risk for melanomas of both the skin and eye1.6%

BRCA2 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines as of the last Myriad update shown on this page. The specific reference provided (e.g., NCCN guidelines) should be consulted for more details and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

Cancer Type Procedure Age to Begin Frequency
Female BreastBreast awareness - Women should be familiar with their breasts and promptly report changes to their healthcare provider. Periodic, consistent breast self-examination (BSE) may facilitate breast awareness.118 yearsNA
Clinical breast examination125 yearsEvery 6 to 12 months
Breast MRI with contrast and/or Mammography1Age 25 for MRI (preferred) or mammography. Age 30 for both MRI and mammography. Individualize to a younger age if a relative has been diagnosed younger than age 30.Annually
Consider investigational screening studies within clinical trials.1IndividualizedNA
Consider risk-reducing mastectomy.1IndividualizedNA
Consider options for breast cancer risk-reduction agents (i.e. tamoxifen).1IndividualizedNA
OvarianBilateral salpingo-oophorectomy135 to 40 years, upon completion of childbearing, or 40 to 45 for women who have already maximized their breast cancer risk preventionNA
Consider transvaginal ultrasound and CA-125 measurement. Consider investigational screening studies within clinical trials.130 to 35 yearsIndividualized
Consider options for ovarian cancer risk-reduction agents (i.e. oral contraceptives).1IndividualizedNA
PancreaticConsider available options for pancreatic cancer screening, including the possibility of endoscopic ultrasonography (EUS) and MRI/magnetic resonance cholangiopancreatography (MRCP). It is recommended that patients who are candidates for pancreatic cancer screening be managed by a multidisciplinary team with experience in the screening for pancreatic cancer, preferably within research protocols.9IndividualizedNA
Male BreastBreast self-examination135 yearsMonthly
Clinical breast examination135 yearsAnnually
ProstateRecommend prostate cancer screening.145 yearsIndividualized
MelanomaConsider whole-body skin and eye examinations.1IndividualizedNA

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the BRCA2 gene.

A major potential benefit of myRisk genetic testing for hereditary cancer risk is the opportunity to prevent cancer in relatives of patients in whom clinically significant mutations are identified. Healthcare providers have an important role in making sure that patients with clinically significant mutations are informed about the risks to relatives, and ways in which genetic testing can guide lifesaving interventions.

In rare instances, an individual may inherit mutations in both copies of the BRCA2 gene, leading to the condition Fanconi Anemia, Complementation Group D1 (FANCD1). This condition is rare and includes physical abnormalities, growth retardation, progressive bone marrow failure and a high risk for cancer. The children of this patient are at risk of inheriting FANCD1 only if the other parent is also a carrier of a BRCA2 mutation. Screening the spouse/partner of this patient for BRCA2 mutations may be appropriate.13

References

  1. Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast and Ovarian. V 1.2017. September 19. Available at http://www.nccn.org.
  2. Surveillance Research Program, National Cancer Institute SEER*Stat software (seer.cancer.gov/seerstat) V 8.0.1, Nov 19, 2012.
  3. Ford D, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet. 1998 62:676-89. PMID: 9497246.
  4. Chen S, et al. Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol. 2006 24:863-71. PMID: 16484695.
  5. Mavaddat N, et al. Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. J Natl Cancer Inst. 2013 105:812-22. PMID: 23628597.
  6. Verhoog LC, et al. Survival in hereditary breast cancer associated with germline mutations of BRCA2. J Clin Oncol. 1999 17:3396-402. PMID: 10550133.
  7. Metcalfe KA, et al. The risk of ovarian cancer after breast cancer in BRCA1 and BRCA2 carriers. Gynecol Oncol. 2005 96:222-6. PMID: 15589605.
  8. van Asperen CJ, et al. Netherlands Collaborative Group on Hereditary Breast Cancer (HEBON) . Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J Med Genet. 2005 42:711-9. PMID: 16141007.
  9. Canto MI, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013 62:339-47. PMID: 23135763.
  10. Tai YC, et al. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2007 99:1811-4. PMID: 18042939.
  11. Gumaste PV, et al. Skin cancer risk in BRCA1/2 mutation carriers. Br J Dermatol. 2015 172:1498-506. Epub 2015 Apr 29. PMID: 25524463.
  12. Moran A, et al. Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations. Fam Cancer. 2012 11:235-42. PMID: 22187320.
  13. Mehta PA, Tolar J. Fanconi Anemia. 2016 Sep 22. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Available from http://www.ncbi.nlm.nih.gov/books/NBK1401/. PMID: 20301575.
Last Updated on 01-Jun-2017
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