Indicators for Genetics Referral for Hereditary Breast Cancer
For a quick review of genetic testing for the BRCA1 and BRCA2 genes for Hereditary Breast and Ovarian Cancer and referral indications.
How common are BRCA1 and BRCA2 mutations in the general population?
Inherited mutations in BRCA1 and BRCA2 are relatively uncommon in the general population. The carrier frequency is estimated to range from 1 in 300 to 1 in 8001,3. Certain ethnic groups have been shown to have a higher carrier frequency (e.g., 1 in 40 individuals of Ashkenazi Jewish descent).
What percentage of breast and ovarian cancer cases are estimated to be caused by BRCA1 and BRCA2 mutations?
Five to 10 percent of all breast cancer cases and up to 14 percent of all ovarian cancer cases are thought to be caused by BRCA1 and BRCA2 mutations.1,2,3,4
What is the risk for breast and ovarian cancer in individuals found to have a BRCA1 or BRCA2 mutation?
For women with a mutation in either BRCA1 or BRCA2, studies have shown the lifetime risk of breast cancer to range from 50 to 87 percent. The lifetime risk of ovarian cancer has been noted to range from 15 to 44 percent, depending on the specific mutation.1
Men with a BRCA mutation have a 5 to 10 percent lifetime risk of developing breast cancer. Men without such mutations have a 0.1 percent lifetime risk.1
Can BRCA1 and BRCA2 mutations be inherited from either side of the family?
Yes, either parent can pass along a BRCA1 or BRCA2 mutation. Therefore, it is important for clinicians to obtain a complete cancer history on both the maternal and the paternal sides of the family when assessing genetic risk.4
Which patients should I consider for risk assessment and to discuss the option of genetic testing for BRCA1 and BRCA2 mutations?
Most individuals do not have a mutation in the BRCA1 or BRCA2 gene. While specific indications for genetic counseling and testing vary among professional organizations, certain aspects of your patient’s personal and/or family history may increase his or her likelihood of carrying a BRCA1 or BRCA2 mutation. The indications below are to be used as a guide and are not a substitute for clinical judgment. Not all clinical scenarios can be anticipated. For instance, genetic testing guidelines may not take into consideration a situation where the family history is limited.6 In addition; individual insurance companies have their own criteria for reimbursement for genetic testing that may not match the indications lists that follow.
Indications include the following1,2,3,5:
A personal history of:
Breast cancer at a young age (younger than age 50) or ovarian cancer at any age,
Bilateral breast cancer or two or more primary tumors of the breast,
Breast and ovarian cancer (in the same individual), or
Breast cancer in a male;
And/or a maternal or paternal family history of:
Two or more individuals in the family (parent, child, sibling, grandparent, aunt/uncle) with breast and/or ovarian cancer,
One or more close male relatives with breast cancer,
Early onset breast or ovarian cancer (before age 50) in a close relative, or
Confirmed BRCA1 or BRCA2 mutation.
Note: Individuals who belong to ethnic groups with increased mutation prevalence, such as those of Ashkenazi Jewish descent, may be appropriate candidates for referral even if they have a less striking personal or family history of breast and/or ovarian cancer.
Ideally, the decision to test should start with the patient’s family member affected with either breast or ovarian cancer, since this helps determine if the cancer is associated with one of the mutations and makes test interpretation more straightforward.1,2,3,4
You may find it helpful to refer to specific genetic testing guidelines published by professional organizations, some of which are listed on the third page of this document.
Genetic testing for breast cancer risk may be complicated by:
The possibility of false negative results, since other genes and mutations carrying similar cancer risk, but not yet discovered or tested for, may be present;
The possibility of test results with mutations noted to have “uncertain clinical significance” (some mutations in the BRCA genes may or may not be of clinical significance);
Cost of BRCA gene testing, which ranges from $440 (single-site analysis) to $3,120 (for full sequencing of both genes); or
Limitations of genetic test results, i.e., they help to quantify an individual’s risk for developing cancer, but they do not provide an individual patient with information regarding if or when or where cancer may develop.4
What are the advantages and disadvantages of BRCA1 and BRCA2 testing?
Testing may clarify risk for specific cancers, allowing for reduction of those risks through early detection and prevention.
Patients with a BRCA gene mutation would benefit from prophylactic surgeries.
For families with a known mutation, a negative test result reduces the patient’s risk of breast and ovarian cancer to that of the general population.
Testing may help patients focus on the medical and lifestyle choices available to them (earlier/increased screening, chemoprevention, surgical options).
Testing may help inform other family members about their potential cancer risk.
Testing may lead to an increased sense of control and decreased stress for the patient.
For cancer patients, a positive test result may decrease feelings of self-blame.
Testing may cause a patient to experience stress.
Testing positive may result in guilt or fear over possibly passing a mutation to children.
Without appropriate counseling, individuals with a negative test result may think they have no chance of getting cancer and thus forgo appropriate screening tests.
What are the benefits of genetic counseling when offering BRCA1 and BRCA2 testing?
Patient education and informed consent are critical aspects of the genetic testing process and will help individuals decide if genetic testing is right for them. Pretest counseling should address the implications of potential test results, medical management, psychosocial aspects, other options for testing, and testing costs. Post-test genetic counseling should address cancer risk estimates and subsequent medical management recommendations based on the genetic test results. When a BRCA1 or BRCA2 mutation has been identified, post-test genetic counseling also should include facilitating the dissemination of this information to at-risk family members.
How can I find a genetic counselor in my area for my patients?
Genetic counselors are master’s-trained individuals that are board certified by the American Board of Genetic Counselors. Search under Texas Genetics Providers.
What is GINA — Genetic Information Nondiscrimination Act?
GINA is a new federal law passed by President George W. Bush in May 2008 that provides patients additional protection against genetic discrimination in regards to health insurance and employment. Other state and federal laws provide this protection as well. GINA paves the way for people to take advantage of the promise of personalized medicine without fear of discrimination. However, currently no state or federal legislation regarding genetic discrimination applies to life insurance and disability insurance.
For More Information
BRCA1 and BRCA2 testing and risk management guidelines
National Comprehensive Cancer Network (these guidelines also contain information on managing patients found positive for BRCA1 or BRCA2)
U.S. Preventive Services Task Force
National Cancer Institute (NCI)
About genetic testing for breast and ovarian cancer
National Cancer Institute Fact Sheets
Centers for Disease Control and Prevention
National Institute of Health — Genetics Through a Primary Care Lens: A Web-Based Resource for Faculty Development at www.genetests.org (select Genetic Tools in the right tool bar)
- Berliner JL et al (2007). Risk Assessment and Genetic Counseling for Hereditary Breast and Ovarian Cancer: Recommendations of the National Society of Genetic Counselors. Journal of Genetic Counseling, 16:241-260.
- Centers for Disease Control and Prevention. Fact Sheet on Genetic Testing for Breast and Ovarian Cancer Susceptibility.
- National Cancer Institute. Genetic Testing for BRCA 1 and BRCA 2: It’s Your Choice. Located June 11, 2007 at www.cancer.gov/cancertopics/factsheet/Risk/BRCA/print?page=&keyword.
- Pinsky LE et al (2001). Why Should Primary Care Physicians Know About Breast Cancer Genetics? Western Journal of Medicine, 175:168-173.
- Guidelines listed in above resource list.
- Weitzel JN et al (2007). Limited Family Structure and BRCA Gene Mutation Status in Single Cases of Breast Cancer. JAMA, 297(23):2587-2695.
Guidelines for Screening for Hereditary Colon Cancer
A personal or family history of:
Colon cancer before the age of 45,
Pre-cancerous polyps before the age of 40,
More than 20 pre-cancerous polyps
Uterine cancer before the age of 45
Three or more people in the family with colon, uterine, stomach or ovarian cancer
Confirmed genetic mutation in a relative.
Medicare criteria for genetic testing for Lynch Syndrome
Personal History of Colorectal or Endometrial Cancer, plus one of the following:
2 relatives with an HNPCC-associated cancer, plus all of the following:
+ One must be a 1st degree relative of the other two; and
+ At least two successive generations must be affected; and
+ At least one of the relatives (or patient) should be diagnosed before age 50; and
+ FAP should be excluded in the colorectal cases
Has had a second HNPCC-associated malignancy
Has a blood relative with a known HNPCC-related gene mutation
If MSI-H and/or IHC positive colon tumor
Medicare criteria for genetic testing for FAP
NCCN Clinical Practice Guidelines for Familial High-Risk Assessment of Breast and Ovarian Cancer
American Society of Clinical Oncology Policy Statement on Genetic Testing for Cancer Susceptibility
National Society of Genetic Counselors Recommendations on Risk Assessment and Genetic Counseling for Hereditary Breast and Ovarian Cancer
Professional Genetic Societies
American College of Medical Genetics
Texas Society of Genetic Counselors
Texas Genetics Society
A World of Genetics Societies
Offers links to most genetic societies including: The Genetics Society of America, The American College of Medical Genetics, The American Board of Medical Genetics, The American Board of Genetic Counseling, Association of Professors of Human or Medical Genetics.
American Society of Human Genetics
Brings together investigators in the many areas of endeavor that involve human genetics, and to encourage and integrate their efforts by providing a forum for sharing research findings.
National Coalition for Health Professional Education in Genetics (NCHPEG)
A resource of educational links to help health care professionals learn more about the field of genetics.
National Society of Genetic Counselors, Inc.
Represents the leading voice, authority and advocate for the genetic counseling profession.
US Government Websites
United State Department of Health and Human Services
The Surgeon General’s office developed a computer tool called “My Family Health Portrait” to assist families in recording their family tree and medical illness.
Centers for Disease Control and Prevention
CDC serves as the national focus for developing and applying disease prevention and control, environmental health, and health promotion and education activities designed to improve the health of the people of the United States.
National Center for Health Statistics
NCHS is the Federal Government's principal vital and health statistics agency.
Genetics and Public Health in the 21st Century
Using Genetic Information to Improve Health and Prevent Disease.
Health Resources and Services Administration
HRSA assures the availability of quality health care to low income, uninsured, isolated, vulnerable and special needs populations and meets their unique health care needs.
Maternal and Child Health Bureau
MCHB provides leadership, partnership, and resources to advance the health of all our Nation's mothers, infants, children and adolescents-including families with low income levels, those with diverse racial and ethnic heritages and those living in rural or isolated areas without access to care.
National Institutes of Health
The goal of NIH research is to acquire new knowledge to help prevent, detect, diagnose, and treat disease and disability, from the rarest genetic disorder to the common cold.
National Human Genome Research Institute
NHGRI was originally established in 1989 as The National Center for Human Genome Research (NCHGR). Its mission is to head the Human Genome Project for NIH.
Online Mendelian Inheritance in Man
This database is a catalog of human genes and genetic disorders. The database contains textual information, pictures, and reference information.
US Census Bureau
The preeminent collector and provider of timely, relevant, and quality data about the people and economy of the United States.
By providing current, authoritative information on genetic testing and its use in diagnosis, management, and genetic counseling, GeneTests-GeneClinics promotes the appropriate use of genetic services in patient care and personal decision-making.
Genetic and Rare Conditions Site
upplies an alphabetical listing of information on genetic conditions and birth defects to professionals, educators, or anyone interested in knowing more.
Genetics Education Center
For educators interested in human genetics and the human genome project.
Established at Johns Hopkins University in Baltimore, Maryland, USA in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative.
MendelWeb is an educational resource for teachers and students interested in the origins of classical genetics, introductory data analysis, elementary plant science, and the history and literature of science.
The Genetic Alliance is an international coalition of individuals, professionals and genetic support organizations that are working together to promote healthy lives for everyone impacted by genetics.
American Association of University Affiliated Programs for Persons with Developmental Disabilities
A network of interdisciplinary Centers advancing policy and practice for and with individuals with developmental and other disabilities, their families, and communities.
American Academy of Pediatrics
A national organization for pediatricians.
National Birth Defects Prevention Network
The National Birth Defects Prevention Network (NBDPN) is a group of individuals involved in birth defects surveillance, research, and prevention.
External links to other sites are intended to be informational and do not have the endorsement of the Texas Department of State Health Services. These sites may not be accessible to persons with visual impairment.