Genetic Susceptibility to Breast and Ovarian Cancer - Guidelines, Algorithm and Questionnaire

The first encounter with every patient should elicit a detailed three-generation family cancer history to determine whether increased risk for breast/ovarian cancer is apparent. If an increased risk is suggested, the health care professional must assure that the patient receive appropriate cancer risk assessment and education as part of the pre-test consideration process. In addition, initial discussions with such patients should address their questions, concerns, and expectations regarding the implications of genetic testing and testing outcomes.

Further, the health care provider must assure that comprehensive post-test counseling is available to patients found to be mutation-positive, as well as to those with negative or uncertain test results. The clinician may choose to handle all aspects him or herself, or may work in concert with an expert in cancer genetic counseling and risk assessment. The necessary steps are outlined in the accompanying Algorithm.

Responsibilities of provider offering testing:

  • Risk assessment
  • Pre-test education
  • Post-test counseling

Risk Assessment

  • Risk assessment should begin with estimating the likelihood of developing breast or ovarian cancer through a complete personal and family cancer history (see accompanying sample questionnaire). The family cancer history should include all first degree relatives (parents, siblings and children) and second degree relatives (grandparents, grandchildren, aunts and uncles, half-siblings, nieces and nephews) and cover at least three generations. It should include all types of cancer and approximate age at diagnosis for each affected individual. Where possible, documentation through review of medical records, pathology and autopsy reports is recommended. It is essential that both maternal and paternal sides of the family be assessed, as breast and/or ovarian cancer risk can be transmitted through the patient's father or mother.
  • The likelihood of having a mutation in a known cancer susceptibility gene (e.g. BRCA1 or BRCA2) should be assessed on the basis of the number of family members with breast or ovarian cancer, the closeness of relationship to the patient, the ages at diagnosis, and other factors, such as whether or not the individual is a member of an ethnic group at higher risk for specific mutations, such as Ashkenazi (Eastern or Central European) Jewish descent, or whether other related cancers have occurred in the family.
  • Increased risk for a mutation in a known cancer susceptibility gene is evident if:
    • There are three or more affected first or second degree relatives on the same side of the family, regardless of age at diagnosis, or
    • There are fewer than three affected relatives, but
      • the patient was diagnosed at 45 years of age or less, or
      • a family member has been identified with a detectable mutation, or
      • there are one or more cases of ovarian cancer at any age, and one or more members on the same side of the family with breast cancer at any age, or
      • there are multiple primary or bilateral breast cancers in the patient or one family member, or
      • there is breast cancer in a male patient, or in a male relative, or
      • the patient is at increased risk for specific mutation(s) due to ethnic background (for instance: Ashkenazi Jewish descent) and has one or more relatives with breast cancer or ovarian cancer at any age.
  • Individuals not at increased risk for having an inherited mutation in BRCA1 or BRCA2 must be advised of background risk figures and provided reassurance that their risk is comparable to that of the general population. Surveillance measures recommended for all adult women should be reviewed (see Table I). The provider and individual considering testing should do so only when a significantly increased risk exists, unless the patient's anxiety or other concerns indicate the need for further discussion.
  • Candidates for genetic testing should at least be up-to-date with regard to the American Cancer Society surveillance recommendations for their age group (see Table I). Many experts recommend that women with a first degree relative or relatives with breast cancer start annual mammography at an age ten years younger than the earliest age of onset in the family. While this may be reasonable advice, there are no data to demonstrate or refute the effectiveness of this recommendation.
  • Except in unusual circumstances, it is not generally recommended that individuals under 18 be tested since there is no recommended intervention in childhood.

Risk Assessment And Genetic Counseling

Table I - American Cancer Society's 1997 Guidelines
The most recent American Cancer Society recommendations for the early detection of breast cancer are:
Age <40: Monthly Breast Self-Exam Clinical Breast Exam Every Three Years
Age 40+: Monthly Breast Self-Exam Yearly Clinical Breast Exam Yearly Mammogram
  • When an increased risk for hereditary susceptibility is identified through the individual or family history, the clinician should initiate discussion or refer the patient for information concerning genetic testing and its potential benefits and burdens. The clinician who opts to take on this responsibility must provide the depth of content and time required to ensure that the patient can make an informed choice.
  • Before testing, adults ascertained to be at increased risk must undergo a process of pre-test education so that they can make an informed choice; i.e., decide for themselves whether the potential benefits of testing are likely to outweigh the potential burdens. The elements of pre-test education include:
    • clarification of patient's increased risk status
    • explanation of how genetics affects cancer susceptibility
    • potential benefits, risks, and limitations of testing
    • possible outcomes of testing (positive, negative, or uncertain test result)
    • limited data on efficacy of methods (such as prophylactic mastectomy and/or oophorectomy) for early detection and prevention
    • possible psychological and social impact of testing
    • alternatives to genetic testing
  • It is essential that candidates for testing be alerted to the difficulty of assuring the confidentiality of the results and to the possibility of discrimination by insurers or employers. Existing or anticipated legislation may substantially reduce these testing-associated burdens.
  • Enhanced interaction between primary care and genetics services providers is desirable (see Table 1). The National Cancer Institute, reachable through 1-800-4-CANCER, can provide practitioners with referrals to centers and/or colleagues specializing in the area of cancer genetics.
  • All individuals found to be at increased risk, whether they choose testing or not, should be encouraged to consider participation in clinical research efforts. Such longitudinal follow-up is expected to improve our understanding of the natural history associated with these mutations, and of the efficacy of various interventions. Psychological sequelae experienced by patients choosing various options should also be studied through this means.

Testing

  • If the patient has not had breast or ovarian cancer, a closely related family member who has had breast or ovarian cancer should be tested first whenever feasible. If there is not a living affected relative, it may be possible to study fixed tumor tissue from a deceased relative. A negative result in the patient is most informative when a familial mutation has first been identified.
  • Following pre-test counseling, the patient should be given sufficient time to evaluate and incorporate this information before deciding about testing. Therefore, separate visits are recommended for pre-test education and testing.
  • Before testing proceeds, written informed consent must be obtained to document the education and counseling process.
  • The selection of a laboratory for DNA testing for cancer susceptibility must take into account state regulations and institutional policies. Specifications for drawing and shipping blood or other types of specimens and information on the nature and limitations of testing must be obtained from the specific laboratory.

Post-Test Counseling

  • All individuals choosing to be tested must receive their results in person, regardless of the results.
  • An individual found to have a deleterious mutation should be provided a) a full explanation and interpretation of the test results based on current knowledge, b) psychological support, c) alternatives directed toward early detection and/or prevention, and d) information concerning testing of close adult relatives.
  • In the case of test results indicating an alteration of unknown significance, it is critical to test additional family members, with and without breast and/or ovarian cancer, to assess the significance of the identified alteration.
  • If the test indicates that the patient does not have the mutation identified in an affected relative, the individual must be cautioned that she still has the background risk for breast and ovarian cancer found in the general population, and standard surveillance should be continued.
  • If no affected family member has been tested, and no mutation is detected in the person at risk, the tested individual must be cautioned that an increased genetic risk has not been eliminated and that an increased level of surveillance should be maintained.