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Nelson HD, Fu R, Goddard K, et al. Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: Systematic Review to Update the U.S. Preventive Services Task Force Recommendation [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2013 Dec. (Evidence Syntheses, No. 101.)
Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: Systematic Review to Update the U.S. Preventive Services Task Force Recommendation [Internet].
Show detailsAppendix A1. Referral Criteria, Adapted From National Comprehensive Cancer Network Guidelines50
Table 1Criteria for Further Genetic Risk Evaluation
| a) Unaffected individual and a family history of ≥1 of these: | ≥2 breast primaries, either in 1 individual or 2 different individuals from the same side of family (maternal or paternal) |
| ≥1 ovarian cancer primary from the same side of the family (maternal or paternal) | |
| First- or second-degree relative with breast cancer age ≤45 years | |
| A combination of breast cancer with ≥1 of the following: thyroid cancer, sarcoma, adrenocortical carcinoma, endometrial cancer, pancreatic cancer, brain tumor, diffuse gastric cancer, dermatologic manifestations and/or marocephaly, or leukemia/lymphoma on the same side of the family (especially if early-onset) | |
| A known mutation in a breast cancer susceptibility gene within the family | |
| Male breast cancer | |
| b) Individuals at increased risk, may have modified inclusion (e.g., Ashkenazi Jewish with above at any age) | |
- One or more of these criteria is suggestive of hereditary breast/ovarian cancer (HBOC) syndrome that warrants further personalized risk assessment, genetic counseling, and management. The maternal and paternal sides should be considered independently. Other malignancies reported in some HBOC families include prostate and melanoma.
- Individuals with limited family history, such as less than 2 first- or second-degree female relatives or female relatives surviving beyond age 45 years in either lineage, may have an underestimated probability of familial mutation.
- For the purposes of these guidelines, invasive and ductal carcinoma in situ breast cancer should be included.
- Close blood relatives include first-, second-, and third-degree relatives.
- For the purposes of these guidelines, fallopian tube and primary peritoneal cancer are included. Ovarian/fallopian tube/primary peritoneal cancer are component tumors of hereditary nonpolyposis colorectal cancer/Lynch syndrome; be attentive for clinical evidence of this syndrome.
- Two breast primaries include bilateral (contralateral) disease or 2 or more clearly separate ipsilateral primary tumors either synchronously or asynchronously.
Table 2Criteria for Genetic Testing for HBOC Syndrome
| a) Individual from a family with a known deleterious BRCA1 or BRCA2 mutation | |
| b) Personal history of breast cancer and ≥1 of these: | Diagnosed at age ≤45 years |
| Diagnosed at age ≥50 years with ≥1 close blood relatives with breast cancer at age 50 years and/or ≥1 close blood relatives with epithelial ovarian cancer at any age | |
| 2 breast primaries when first breast cancer diagnosis occurred at age ≤50 years | |
| Diagnosed at age ≤60 years with a triple negative breast cancer | |
| Diagnosed at age ≤50 years with a limited family history | |
| Diagnosed at any age, with ≥2 close blood relatives with breast and/or epithelial ovarian cancer at any age | |
| Diagnosed at any age with ≥2 close blood relatives with pancreatic cancer at any age | |
| Close male blood relative with breast cancer | |
| Individual of ethnicity associated with higher mutation frequency (e.g., Ashkenazi Jewish) | |
| Personal history of epithelial ovarian cancer | |
| Personal history of male breast cancer | |
| Personal history of pancreatic cancer at any age with ≥2 close blood relatives with breast and/or ovarian cancer and/or pancreatic cancer at any age | |
| c) No personal history of breast cancer, but ≥1 of these: | First- or second-degree blood relative meeting any of the above criteria |
| Third-degree blood relative with breast cancer and/or ovarian cancer with ≥2 close blood relatives with breast cancer (≥1 with breast cancer at age ≤50 years) and/or ovarian cancer | |
- Testing of unaffected family members should only be considered when no affected family member is available, and then the unaffected family member with the highest probability of mutation should be tested. Significant limitations of interpreting test results should be discussed.
- Testing for Ashkenazi Jewish founder-specific mutation(s) should be performed first. Full sequencing may be considered if ancestry also includes nonAshkenazi Jewish relatives or other HBOC criteria are met. Founder mutations exist in other populations.
- Individuals with limited family history, such as less than 2 first- or second-degree female relatives or female relatives surviving beyond age 45 years in either lineage, may have an underestimated probability of familial mutation.
- For the purposes of these guidelines, invasive and ductal carcinoma in situ breast cancer should be included.
- Close blood relatives include first-, second-, and third-degree relatives.
- For the purposes of these guidelines, fallopian tube and primary peritoneal cancer are included. Ovarian/fallopian tube/primary peritoneal cancer are component tumors of hereditary nonpolyposis colorectal cancer/Lynch syndrome; be attentive for clinical evidence of this syndrome.
- Two breast primaries include bilateral (contralateral) disease or 2 or more clearly separate ipsilateral primary tumors either synchronously or asynchronously.
Appendix A2. Definitions of Terms Used in Systematic Review
| Term or Phrase | Definition |
|---|---|
| BRCA-related cancer | Predominantly breast, ovarian, fallopian tube, and peritoneal |
| Genetic counseling | A service delivered by a qualified health professional that provides a comprehensive evaluation of familial risk for inherited disorders using kindred analysis and other methods, patient education, discussion of the benefits and harms of genetic testing, interpretation of results after testing, and discussion of management options |
| True negative test | Known confirmed deleterious genetic mutation in relatives, and none detected in the patient |
| Uninformative negative test | No known deleterious genetic mutations in relatives, and none detected in the patient |
| Variant of uncertain significance | An abnormality of the BRCA1 or BRCA2 gene, but it is not known whether it is associated with an increased risk for cancer |
| Analytic validity* | Technical test performance measured by analytic sensitivity and specificity, reliability, and assay robustness |
| Clinical validity* | The test's ability to accurately and reliably predict the future disorder measured by clinical sensitivity and specificity, and predictive values of positive and negative tests that take into account the disorder prevalence |
| Clinical utility* | Balance of benefits and harms when the test is used to influence patient management. For risk assessment, clinical utility is determined by improved health outcomes based on prevention or early detection strategies |
- *
Defined by the Centers for Disease Control and Prevention. Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group for tests of risk assessment/susceptibility. Genet Med. 2009;11:3–14. [PMC free article: PMC2743609] [PubMed: 18813139].
- Referral Criteria and Definitions of Terms - Risk Assessment, Genetic Counseling...Referral Criteria and Definitions of Terms - Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer
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