Genetic counseling and testing for hereditary breast and ovarian cancer
- Beth N Peshkin, MS, CGC
Beth N Peshkin, MS, CGC
- Professor of Oncology, Senior Genetic Counselor
- Georgetown University Medical School
- Jess and Mildred Fisher Center for Hereditary Cancer and Clinical Genomics Research
- Claudine Isaacs, MD
Claudine Isaacs, MD
- Professor of Medicine and Oncology
- Georgetown University Medical School
- Jess and Mildred Fisher Center for Hereditary Cancer and Clinical Genomics Research
- Section Editors
- Anees B Chagpar, MD, MSc, MA, MPH, MBA, FACS, FRCS(C)
Anees B Chagpar, MD, MSc, MA, MPH, MBA, FACS, FRCS(C)
- Section Editor — Breast Surgery
- Associate Professor, Department of Surgery
- Yale University School of Medicine
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Professor of Gynecologic Oncology
- University of Washington
The most common cause for hereditary breast and ovarian cancers is the presence of germline mutations in the tumor suppressor genes and breast cancer type 1 and 2 susceptibility genes (BRCA1 and BRCA2). However, in clinical practice, the vast majority of women who undergo genetic testing do not have a mutation in either one of these genes.
Genetic analysis is performed at various commercial laboratories nationally and internationally . Since 2013, when the Supreme Court of the United States invalidated key patents on BRCA1 and BRCA2 held by a commercial company, more testing options have become available. In addition to BRCA1 and BRCA2 tests, next-generation sequencing (NGS) multigene panels are also available to evaluate a wider array of potential mutations that might predispose to breast and/or ovarian cancer.
For patients who meet criteria for genetic testing (and those who desire genetic testing), expertise is required to ensure that the test will be adequately interpreted and that the results will aid in diagnosis or influence management of the patient or family members at risk for hereditary cancer . The complexity involved in pre- and post-test risk assessment underscores the importance of genetic counseling both before and after testing.
This topic reviews the genetic testing and the interpretation of genetic tests for hereditary breast and ovarian cancer syndrome suspected as being associated with mutations in BRCA1 or BRCA2.
CRITERIA FOR GENETIC RISK EVALUATION
While unaffected women often present with concerns about their hereditary cancer risk, whenever possible, it is ideal to initiate genetic testing in a family member who is most likely to test positive for a mutation, which is usually a woman affected by early breast cancer or ovarian cancer (any age). Most hereditary breast and ovarian cancers (HBOC) are due to highly penetrant germline BRCA mutations, which are inherited in an autosomal-dominant fashion. Data regarding clinical characteristics associated with BRCA mutations are discussed elsewhere (See "Prevalence of BRCA1 and BRCA2 mutations and associated cancer risks", section on 'Clinical characteristics associated with BRCA mutations'.)
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- CRITERIA FOR GENETIC RISK EVALUATION
- GENETIC COUNSELING
- Pre-test counseling
- - Pedigree evaluation
- Risk assessment models
- Issues for patients considering testing
- Post-test counseling
- OPTIONS FOR GENETIC TESTING
- BRCA1 and BRCA2 testing
- Assessment of large genomic rearrangements in BRCA
- Next-generation panel testing
- Other options
- INTERPRETATION OF TEST RESULTS
- Positive results
- True negative results
- Uninformative (negative) result
- Variants of uncertain significance
- APPROACH TO PATIENTS WITH UNINFORMATIVE RESULTS
- Cancer risk assessment of patients with uninformative (negative) test results
- - No personal history of cancer
- - Personal history of breast cancer
- - Personal or family history of ovarian cancer
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS