BRCA1/2 associated cancer susceptibility: a clinical overview

Lypas, Georgios

doi:10.1515/fco-2015-0022

Figures & Tables

BRCA1/2 associated cancer risks_

Cancer Type	General Population Risk	Mutation Risk
Cancer Type	General Population Risk	BRCA1	BRCA2
Breast	12%	50%-80%	40%-70%
Second primary breast	3.5% within 5 years Up to 11%	27% within 5 yrs	12% within 5 yrs 40%-50% at 20 yrs
Ovarian	1%-2%	24%-40%	11%-18%
Male breast	0.1%	1%-2%	5%-10%
Prostate	15% (N. European origin)18% (African Americans)	<30%	<39%
Pancreatic	0.50%	1%-3%	2%-7%

Elements of informed consent for genetic testing of cancer susceptibility [39]_

Information on the specific genetic mutation(s) or genomic variant(s) being tested, including whether the range of risk associated with the variant will impact medical care
Implications of a positive and negative result
Possibility that the test will not be informative
Options for risk estimation without genetic or genomic testing
Risk of passing a genetic variant to children
Technical accuracy of the test including, where required by law, licensure of the testing laboratory
Fees involved in testing and counseling and, for DTC testing, whether the counsellor is employed by the testing company
Psychological implications of test results (benefits and risks)
Risks and protections against genetic discrimination by employers or insurers
Confidentiality issues, including, for DTC testing companies, policies related to privacy and data security
Possible use of DNA testing samples in future research
Options and limitations of medical surveillance and strategies for prevention after genetic or genomic testing
Importance of sharing genetic and genomic test results with at-risk relatives so that they may benefit from this information
Plans for follow-up after testing

Nccn testing criteria [16]_

Individual from a family with a known deleterious BRCA1/BRCA2 mutation
*
One or more of these criteria is suggestive of hereditary breast/ovarian cancer syndrome that warrants further personalised risk assessment, genetic counselling, and often genetic testing and management. The maternal and paternal sides should be considered independently. Melanoma has been reported in some hereditary breast/ovarian cancer families.
•
Patients who have received an allogeneic bone marrow transplant should not have molecular genetic testing via blood or buccal samples due to unreliable test results from contamination by donor DNA. If available, DNA should be extracted from a fibroblast culture. If the source of DNA is not possible, buccal samples can be considered, subject to the risk of donor DNA contamination.
Δ
Individuals with a limited family history, such as fewer than two first- or second-degree female relatives or female relatives surviving beyond 45 years in either lineage, may have an underestimated probability of a familial mutation.
Personal history of breast cance
♢
For the purposes of these guidelines, invasive and ductal carcinoma in situ breast cancers should be included.
plus one or more of the following:
- Diagnosed age ≤45 years
- Diagnosed age ≤50 years with ≥1 first-, second-, or third-degree blood relative (on the same side of the family) with breast and/or epithelial ovarian/ fallopian tube/primary peritoneal cancer at any age, or with a limited family historyΔ
- Two breast primaries
  §
  Two breast primaries include bilateral (contralateral) disease or two or more clearly separate ipsilateral primary tumors either synchronously or asynchronously.
  when first breast cancer diagnosis occurred ≤50 years
- Diagnosed ≤60 years with a triple negative breast cancer
- Diagnosed ≤50 years with a limited family historyΔ
- Diagnosed at any age with ≥1 first-, second-, or third-degree blood relative (on the same side of the family) diagnosed with breast and/or epithelial ovarian/fallopian tube/primary peritoneal cancer ≤50 years
- Diagnosed at any age with ≥2 first-, second-, or third-degree blood relatives (on the same side of the family) with breast and/or epithelial ovarian/ fallopian tube/primary peritoneal cancer at any age
- Diagnosed at any age with ≥2 first-, second-, or third-degree blood relatives (on the same side of the family) with pancreatic cancer or aggressive prostate cancer (Gleason score ≥7) at any age
- First-, second-, or third-degree male blood relative (on the same side of the family) with breast cancer
- For an individual of ethnicity associated with higher mutation frequency (e.g. Ashkenazi Jewish), no additional family history may be required
  ¥
  Testing for Ashkenazi Jewish founder-specific mutation(s) should be performed first. Full sequencing may be considered if ancestry also includes non-Ashkenazi Jewish relatives or other hereditary breast/ovarian cancer criteria are met. Founder mutations exist in other populations.
Personal history of epithelial ovarian/fallopian tube/primary peritoneal cancer
Personal history of male breast cancer
Personal history of pancreatic cancer or aggressive prostate cancer (Gleason score ≥7) at any age with ≥2 first-, second-, or third-degree blood relatives (on the same side of the family) with breast and/or ovarian cancer and/or pancreatic cancer or aggressive prostate cancer (Gleason score ≥7) at any age
F. Family history only
‡
Clinical judgement should be used to determine if the patient has reasonable likelihood of mutation, considering the unaffected patient’s current age and the age of the female unaffected relatives who link the patient with the affected relatives. Testing of unaffected individuals should only be considered when an appropriate affected member is unavailable for testing. Significant limitations of interpreting test results for an unaffected individual should be discussed.
:
- First- or second-degree blood relative meeting any of the above criteria
- Third-degree blood relative with breast cancer
  ♢
  For the purposes of these guidelines, invasive and ductal carcinoma in situ breast cancers should be included.
  and/or ovarian/fallopian tube/primary peritoneal cancer with ≥2 first-, second-, or third-degree blood relatives (on the same side of the family) with breast cancer (at least one breast cancer ≤50 years) and/or ovarian/fallopian tube/primary peritoneal cancer

BRCA1/2 associated cancer susceptibility: a clinical overview

Figures & Tables

BRCA1/2 associated cancer risks_

Elements of informed consent for genetic testing of cancer susceptibility [39]_

Nccn testing criteria [16]_

Paradigm

My account