Referral Information for Providers

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 800^1,3. Certain ethnic groups have been shown to have a higher carrier frequency (e.g., 1 in 40 individuals of Ashkenazi Jewish descent).

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

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

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

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 following^1,2,3,5:

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

Test advantages

• 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.

Test disadvantages

• 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.

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.

Genetic counselors are master’s-trained individuals that are board certified by the American Board of Genetic Counselors. Search under Texas Genetics Providers.

GINA is a new federal law passed by President George W. Bush in May 2008 that provides patients additional protection against genetic discrimination in regard 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.