BRCA1 gene
Associated Syndrome Name: Hereditary Breast and Ovarian Cancer syndrome (HBOC)
BRCA1 Summary Cancer Risk Table
| Cancer | Genetic Cancer Risk |
| Female Breast | High Risk |
| Ovarian | High Risk |
| Male Breast | Elevated Risk |
| Pancreatic | Elevated Risk |
| Prostate | Elevated Risk |
BRCA1 gene Overview
Hereditary Breast and Ovarian Cancer syndrome (HBOC) 1, 2 - 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. Additionally, men with a BRCA1 mutation have a higher risk for an aggressive prostate cancer.
- Male and female patients with HBOC due to mutations in BRCA1 have an elevated risk for pancreatic cancer.
- Women with HBOC due to mutations in BRCA1 may have an elevated risk for serous uterine cancer, but the data are not conclusive.
- 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 3 |
| Female Breast | To age 504, 5, 6 | 28%-51% | 1.9% |
| To age 705, 6, 7 | 46%-87% | 7.1% |
| Second primary within 5 years of first breast cancer diagnosis8, 9 | 13%-20% | 2% |
| Ovarian | To age 504, 5, 9 | 8%-23% | 0.2% |
| To age 704, 5, 6 | 39%-63% | 0.7% |
| Ovarian cancer within 10 years of a breast cancer diagnosis10 | 12.7% | <1.0% |
| Prostate | To age 7011, 12 | Up to 16% | 6.6% |
| Male Breast | To age 7013 | 1.2% | <0.1% |
| Pancreatic | To age 8014 | Elevated risk | 1% |
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
(Unless otherwise indicated by findings) |
| Female Breast | Breast 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.1 | 18 years | NA |
| Clinical breast examination1 | 25 years | Every 6 to 12 months |
| Breast MRI with contrast and/or mammography with consideration of tomosynthesis1 | Age 25 for MRI, or if MRI is unavailable, mammography with consideration of tomosynthesis. 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.1 | Individualized | NA |
| Consider risk-reducing mastectomy.1 | Individualized | NA |
| Consider options for breast cancer risk-reduction agents (i.e. tamoxifen).1 | Individualized | NA |
| Ovarian | Bilateral salpingo-oophorectomy, including discussion of hysterectomy considering the possible increased risk for serous uterine cancer1 | 35 to 40 years, upon completion of childbearing | NA |
| Consider transvaginal ultrasound and CA-125 measurement. Consider investigational screening studies within clinical trials.1 | 30 to 35 years | Individualized |
| Consider options for ovarian cancer risk-reduction agents (i.e. oral contraceptives).1, 23 | Individualized | NA |
| Prostate | Consider prostate cancer screening.1, 2 | 45 years | Individualized |
| Since mutation carriers are at an increased risk for more aggressive prostate cancer this information may be included as part of the risk and benefit discussion about prostate cancer screening.2, 15 | NA | NA |
| Since mutation carriers are at an increased risk for more aggressive prostate cancer this information may be considered when choosing management options for men with a diagnosis of prostate cancer.2, 15 | NA | NA |
| Male Breast | Breast self-examination1 | 35 years | Monthly |
| Clinical breast examination1 | 35 years | Annually |
| Pancreatic | For patients with a family history of pancreatic cancer, consider 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.21, 22 | Age 50, or 10 years younger than the earliest age of pancreatic cancer diagnosis in the family | Annually |
| Provide education about smoking cessation to reduce pancreatic cancer risk22 | Individualized | Individualized |
| For Patients With A Cancer Diagnosis | For patients with a gene mutation and a diagnosis of cancer, targeted therapies may be available as a treatment option for certain tumor types (e.g., platinum chemotherapy, PARP-inhibitors)15, 16, 17, 18, 19, 20 | NA | NA |
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.
Parents who are concerned about the possibility of passing on a BRCA1 mutation to a future child may want to discuss options for prenatal testing and assisted reproduction techniques, such as pre-implantation genetic diagnosis (PGD).1
References
- Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast and Ovarian. V 2.2019. July 30. Available at http://www.nccn.org.
- Giri VN, et al. Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017. J Clin Oncol. 2018 36:414-424. PMID: 29236593.
- Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. https://seer.cancer.gov/faststats. (Accessed on 1-2-2017)
- 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.
- 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.
- 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.
- Ford D, et al. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet. 1994 343:692-5. PMID: 7907678.
- Verhoog LC, et al. Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1. Lancet. 1998 351:316-21. PMID: 9652611.
- Kuchenbaecker KB, et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. JAMA. 2017 317:2402-2416. PMID: 28632866.
- 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.
- 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.
- 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.
- Tai YC, et al. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2007 99:1811-4. PMID: 18042939.
- Lynch HT, et al. BRCA1 and pancreatic cancer: pedigree findings and their causal relationships. Cancer Genet Cytogenet. 2005 158:119-25. PMID: 15796958.
- Mohler JL, et al. NCCN Clinical Practice Guidelines in Oncology®: Prostate Cancer. V 4.2018. August 15. Available at http://www.nccn.org.
- Gradishar WJ et al. NCCN Clinical Practice Guidelines in Oncology®: Breast Cancer. V 1.2018. March 20. Available at http://www.nccn.org.
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208558s002lbl.pdf
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/209115s000lbl.pdf
- Armstrong DK, et al. NCCN Clinical Practice Guidelines in Oncology®: Ovarian Cancer. V 2.2018. March 9. Available at http://www.nccn.org.
- Tempero MA, et al. NCCN Clinical Practice Guidelines in Oncology®: Pancreatic Adenocarcinoma. V 2.2018. July 10. Available at http://www.nccn.org.
- 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.
- Syngal S, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015 110:223-62. PMID: 25645574.
- Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 1.2018. July 12. Available at http://www.nccn.org.
Last Updated on 05-Feb-2019
BRCA2 gene
Associated Syndrome Name: Hereditary Breast and Ovarian Cancer syndrome (HBOC)
BRCA2 Summary Cancer Risk Table
| Cancer | Genetic Cancer Risk |
| Male Breast | High Risk |
| Female Breast | High Risk |
| Pancreatic | High Risk |
| Ovarian | High Risk |
| Prostate | High Risk |
| Melanoma | Elevated Risk |
BRCA2 gene Overview
Hereditary Breast and Ovarian Cancer syndrome (HBOC) 1, 2 - 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 prostate cancer. The increase in prostate cancer risk is most significant at younger ages. Additionally, men with a BRCA2 mutation have a higher risk for an aggressive prostate cancer.
- 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 3 |
| Female Breast | To age 504, 5, 6 | 23%-35% | 1.9% |
| To age 704, 5, 7 | 43%-84% | 7.1% |
| Second primary within 5 years of first breast cancer diagnosis6, 8 | 8%-12% | 2% |
| Ovarian | To age 504, 5, 7 | 0.4%-4% | 0.2% |
| To age 704, 5, 6 | 15%-27% | 0.7% |
| Ovarian cancer within 10 years of a breast cancer diagnosis9 | 6.8% | <1.0% |
| Pancreatic | To age 8010, 11 | 7%, or higher if there is a family history of pancreatic cancer. | 1% |
| Male Breast | To age 7012 | 6.8% | <0.1% |
| Prostate | To age 7013, 14 | 20% | 6.6% |
| Melanoma | To age 8015, 16 | Elevated risk for melanomas of both the skin and eye | 1.6% |
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
(Unless otherwise indicated by findings) |
| Female Breast | Breast 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.1 | 18 years | NA |
| Clinical breast examination1 | 25 years | Every 6 to 12 months |
| Breast MRI with contrast and/or mammography with consideration of tomosynthesis1 | Age 25 for MRI, or if MRI is unavailable, mammography with consideration of tomosynthesis. 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.1 | Individualized | NA |
| Consider risk-reducing mastectomy.1 | Individualized | NA |
| Consider options for breast cancer risk-reduction agents (i.e. tamoxifen).1 | Individualized | NA |
| Ovarian | Bilateral salpingo-oophorectomy1 | 35 to 45 years, upon completion of childbearing | NA |
| Consider transvaginal ultrasound and CA-125 measurement. Consider investigational screening studies within clinical trials.1 | 30 to 35 years | Individualized |
| Consider options for ovarian cancer risk-reduction agents (i.e. oral contraceptives).1, 24 | Individualized | NA |
| Pancreatic | For patients with a family history of pancreatic cancer, consider 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.11, 23 | Age 50, or 10 years younger than the earliest age of pancreatic cancer diagnosis in the family | Annually |
| Provide education about smoking cessation to reduce pancreatic cancer risk23 | Individualized | Individualized |
| Male Breast | Breast self-examination1 | 35 years | Monthly |
| Clinical breast examination1 | 35 years | Annually |
| Prostate | Recommend prostate cancer screening.1, 2 | 40 to 45 years, or 10 years younger than the earliest prostate cancer diagnosis in the family | Annually, or adjusted based on results from first PSA screen |
| Since mutation carriers are at an increased risk for more aggressive prostate cancer this information may be included as part of the risk and benefit discussion about prostate cancer screening.2, 17 | NA | NA |
| Since mutation carriers are at an increased risk for more aggressive prostate cancer this information may be considered when choosing management options for men with a diagnosis of prostate cancer.2, 17 | NA | NA |
| Melanoma | Consider whole-body skin and eye examinations.1 | Individualized | NA |
| For Patients With A Cancer Diagnosis | For patients with a gene mutation and a diagnosis of cancer, targeted therapies may be available as a treatment option for certain tumor types (e.g., platinum chemotherapy, PARP-inhibitors)17, 18, 19, 20, 21, 22 | NA | NA |
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.25
Parents who are concerned about the possibility of passing on a BRCA2 mutation to a future child may want to discuss options for prenatal testing and assisted reproduction techniques, such as pre-implantation genetic diagnosis (PGD).1
References
- Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast and Ovarian. V 2.2019. July 30. Available at http://www.nccn.org.
- Giri VN, et al. Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017. J Clin Oncol. 2018 36:414-424. PMID: 29236593.
- Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. https://seer.cancer.gov/faststats. (Accessed on 1-2-2017)
- 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.
- 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.
- Kuchenbaecker KB, et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. JAMA. 2017 317:2402-2416. PMID: 28632866.
- 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.
- Verhoog LC, et al. Survival in hereditary breast cancer associated with germline mutations of BRCA2. J Clin Oncol. 1999 17:3396-402. PMID: 10550133.
- 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.
- 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.
- 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.
- Tai YC, et al. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2007 99:1811-4. PMID: 18042939.
- 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.
- 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.
- Gumaste PV, et al. Skin cancer risk in BRCA1/2 mutation carriers. Br J Dermatol. 2015 172:1498-506. PMID: 25524463.
- 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.
- Mohler JL, et al. NCCN Clinical Practice Guidelines in Oncology®: Prostate Cancer. V 4.2018. August 15. Available at http://www.nccn.org.
- Gradishar WJ et al. NCCN Clinical Practice Guidelines in Oncology®: Breast Cancer. V 1.2018. March 20. Available at http://www.nccn.org.
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208558s002lbl.pdf
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/209115s000lbl.pdf
- Armstrong DK, et al. NCCN Clinical Practice Guidelines in Oncology®: Ovarian Cancer. V 2.2018. March 9. Available at http://www.nccn.org.
- Tempero MA, et al. NCCN Clinical Practice Guidelines in Oncology®: Pancreatic Adenocarcinoma. V 2.2018. July 10. Available at http://www.nccn.org.
- Syngal S, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015 110:223-62. PMID: 25645574.
- Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 1.2018. July 12. Available at http://www.nccn.org.
- Mehta PA, Tolar J. Fanconi Anemia. 2018 Mar 8. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Available from http://www.ncbi.nlm.nih.gov/books/NBK1401/ PMID: 20301575.
Last Updated on 05-Feb-2019
