Hereditary Breast and Ovarian Cancer syndrome (HBOC)

BRCA1 AND BRCA2 ASSOCIATED CANCER RISKS

 BREASTOVARIANGASTRICCOLORECTALPANCREATICMELANOMAPROSTATEENDOMETRIALOTHER

Additional Information

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

  • 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 Breast To age 503, 4, 5 28%-51% 1.9%
To age 704, 5, 6 46%-87% 7.3%
Second primary within 5 years of first breast cancer diagnosis7 20% 2%
Ovarian To age 503, 4 13%-23% 0.2%
To age 703, 4, 5 39%-63% 0.7%
Ovarian cancer within 10 years of a breast cancer diagnosis8 12.7% <1.0%
Prostate To age 709, 10 Up to 16% 8.2%
Male Breast To age 7011 1.2% <0.1%
Pancreatic To age 8012 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
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 Mammography1 Age 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.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 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 Individualized NA
Prostate Consider prostate cancer screening.1 45 years Individualized
Male Breast Breast self-examination1 35 years Monthly
Clinical breast examination1 35 years Annually
Pancreatic Currently there are no specific medical management guidelines for pancreatic cancer risk in mutation carriers. 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.

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

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
Melanoma Elevated Risk
Prostate Elevated 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 Breast To age 503, 4 23%-28% 1.9%
To age 703, 4, 5 43%-84% 7.3%
Second primary within 5 years of first breast cancer diagnosis6 12% 2%
Ovarian To age 503, 4, 5 0.4%-4% 0.2%
To age 703, 4, 5 16.5%-27% 0.7%
Ovarian cancer within 10 years of a breast cancer diagnosis7 6.8% <1.0%
Pancreatic To age 808, 9 7%, or higher if there is a family history of pancreatic cancer. 1%
Male Breast To age 7010 6.8% <0.1%
Prostate To age 7010 20% 8.2%
Melanoma To age 8011, 12 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
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 Mammography1 Age 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.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 40 years, upon completion of childbearing, or 40 to 45 for women who have already maximized their breast cancer risk prevention 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 Individualized NA
Pancreatic 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.9 Individualized NA
Male Breast Breast self-examination1 35 years Monthly
Clinical breast examination1 35 years Annually
Prostate Recommend prostate cancer screening.1 45 years Individualized
Melanoma Consider whole-body skin and eye examinations.1 Individualized 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.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