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## Complete Summary

#### GUIDELINE TITLE

Genetic cancer risk assessment and counseling: recommendations of the
National Society of Genetic Counselors.

#### BIBLIOGRAPHIC SOURCE(S)

Trepanier A, Ahrens M, McKinnon W, Peters J, Stopfer J, Grumet SC,
Manley S, Culver JO, Acton R, Larsen-Haidle J, Correia LA, Bennett R,
Pettersen B, Ferlita TD, Costalas JW, Hunt K, Donlon S, Skrzynia C,
Farrell C, Callif-Daley F, Vockley CW. Genetic cancer risk assessment
and counseling: recommendations of the National Society of Genetic
Counselors. J Genet Counsel 2004 Apr;13(2):83-114. \[104 references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15604628)

#### GUIDELINE STATUS

This is the current release of the guideline.

### COMPLETE SUMMARY CONTENT

 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

-   Hereditary cancer (hereditary cancer syndromes)

-   Familial cancer

#### GUIDELINE CATEGORY

Counseling\
Prevention\
Risk Assessment

#### CLINICAL SPECIALTY

Family Practice\
Gastroenterology\
Internal Medicine\
Medical Genetics\
Nursing\
Oncology\
Preventive Medicine\
Psychology

#### INTENDED USERS

Advanced Practice Nurses\
Allied Health Personnel\
Physician Assistants\
Physicians\
Psychologists/Non-physician Behavioral Health Clinicians\
Social Workers

#### GUIDELINE OBJECTIVE(S)

-   To present a set of practice recommendations for genetic counselors
    conveying cancer genetic risk assessment and counseling

-   To provide background information about the process of genetic
    counseling and risk assessment for hereditary cancer

#### TARGET POPULATION

Individuals at risk for familial or hereditary cancer

#### INTERVENTIONS AND PRACTICES CONSIDERED

**Cancer Genetic Risk Assessment and Counseling**

1.  Intake

    -   Personal medical history

    -   Family history

2.  Psychosocial assessment

    -   Assessment of risk perception

    -   Process of psychosocial assessment

3.  Cancer risk assessment

    -   Determination of cancer risk

    -   Communication of cancer risk

4.  Molecular testing for hereditary cancer syndromes

    -   Clinical, fee-for-service testing versus research testing

    -   Pretest genetic counseling and obtaining informed consent

    -   Sample collection

    -   Results disclosure and post-test counseling

5.  Follow-up

    -   Medical surveillance

    -   Review of cancer screening guidelines and methods to reduce
        cancer risk

    -   Referral for medical management

#### MAJOR OUTCOMES CONSIDERED

Not stated

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Hand-searches of Published Literature (Primary Sources)\
Hand-searches of Published Literature (Secondary Sources)\
Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

The information contained in this document was derived from an extensive
review of the current literature on cancer genetic risk assessment and
counseling as well as the personal expertise of genetic counselors
specializing in cancer genetics.

The guideline authors searched via MEDLINE the relevant English language
medical and psychosocial literature between 1989 and 2002, with several
key seminal articles from earlier dates. Key words included cancer
genetics, genetic counseling, psychosocial assessment, and gene testing.

Published guidelines and policy statements published by American Society
of Clinical Oncology (ASCO, 1996, 2003), American College of Medical
Genetics (ACMG) Foundation (1999), American Society of Human Genetics
(ASHG, 1994), National Action Plan on Breast Cancer (NAPBC, 1998), and
genetic counseling guidelines developed by genetic counselors in the
state of Washington (adaptation of Marymee et al., 1998), and the Task
Force on Genetic Testing (NIH-DOE/ELSI Task Force, 1997) were also
reviewed. This literature is based on clinical experience, descriptive
studies, and/or reports of expert committees.

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

The literature was reviewed and evaluated for quality according to the
categories outlined by the U.S. Preventive Services Task Force (1995):

I. Evidence obtained from at least one properly designed randomized
controlled trial

II-1. Evidence obtained from well-designed controlled trials without
randomization

II-2. Evidence obtained from well-designed cohort or
case-control-analytic studies, preferably from more than one center or
research group

II-3. Evidence obtained from multiple time series with or without the
intervention

III\. Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

Not stated

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

Not stated

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

Not applicable

#### COST ANALYSIS

A formal cost analysis was not performed and published cost analyses
were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

External Peer Review\
Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

A draft document was made available to the 2,072 members of National
Society of Genetic Counselors (NSGC) for comment in October 2003. The
NSGC membership includes genetic counselors, physicians, nurses,
attorneys, doctors of philosophy, and students.

The revised document was reviewed by the NSGC attorney and the NSGC
Ethics Subcommittee and no conflicts with the NSGC Code of Ethics or
issues regarding legal liability were identified in the final document.
All 20 members of the NSGC Board of Directors unanimously approved the
final document in November 2003.

The authoring committee also sought expert review from genetic
counselors specializing in cancer genetics; members of the American
College of Medical Genetics (ACMG) and the Oncology Nursing Society;
consumer groups; and the Board of Directors and Genetic Services
Committee of the NSGC.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

**[The Cancer Genetic Risk Assessment and Counseling
Process]{.underline}**

**Intake**

The first step of cancer risk assessment and counseling begins with
collection of a client´s personal and family medical history. Intake
information can be obtained via a questionnaire completed prior to a
cancer risk consultation or during the consultation. Collecting
information prior to the consult allows the clinician to obtain
confirmatory medical records and assess the significance of the family
history in advance of the session.

*Personal Medical History*

The table below lists the information to be collected while obtaining
the client´s medical history for individuals with and without a previous
cancer diagnosis. Information to be obtained includes the frequency of
cancer surveillance, the date and results of recent screening
examinations, and details about pertinent environmental exposures such
as occupation, alcohol consumption, tobacco use, and diet.

+-----------------------------------+-----------------------------------+
| **Questions to ask all patients** | **Questions to ask patients who   |
|                                   | have had cancer/or regarding      |
|                                   | relatives with cancer**           |
+===================================+===================================+
| -   Age                           | -   Organ in which tumor          |
|                                   |     developed                     |
| -   Personal History of benign or |                                   |
|     malignant tumors              | -   Age at time of diagnosis      |
|                                   |                                   |
| -   Major illnesses               | -   Number of tumors^a^           |
|                                   |                                   |
| -   Hospitalizations              | -   Pathology, stage, and grade   |
|                                   |     of malignant tumor            |
| -   Surgeries                     |                                   |
|                                   | -   Pathology of benign tumors    |
| -   Biopsy history                |                                   |
|                                   | -   Treatment regimen (surgery,   |
| -   Reproductive history^b^       |     chemotherapy, radiation)      |
|                                   |                                   |
| -   Cancer surveillance           |                                   |
|                                   |                                   |
| -   Environmental exposures       |                                   |
+-----------------------------------+-----------------------------------+

^a^For patients who have developed more than one tumor, it is important
to discriminate whether the additional tumor(s) was a separate primary,
recurrence, or the result of metastatic disease.\
^b^Especially important for women at increased risk of breast, ovarian,
or endometrial cancer. Inquire about age at menarche, age at first live
birth, and history of oral contraceptive use, infertility medications,
or hormone replacement therapy including dosage and duration, age at
menopause.

*Family History*

Procuring and analyzing a genetic pedigree is the cornerstone of cancer
genetic risk assessment. There is a chance of underascertainment of
high-risk families unless an accurate, comprehensive family history is
obtained from both new and returning patients. At minimum, a three- to
four-generation pedigree, including detailed medical information about
the proband´s first-, second-, and, ideally, third-degree relatives
should be obtained. Standardized pedigree nomenclature should be used.
Gathering information about both paternal and maternal family history,
ancestry/ethnicity, and consanguinity is necessary. For relatives who
have had a cancer diagnosis, document health and carcinogen exposure
information (see \"Personal Medical History\" above for information that
should be collected). For relatives who are deceased, note the cause of
death and age.

Erroneous cancer family history reporting has been documented in the
medical literature and can affect medical management and risk
assessment. Accurate family risk assessment requires medical record
confirmation of key cancer diagnoses. Whenever possible, obtain
confirmation of relevant cancer diagnoses in the family prior to genetic
testing. In the absence of medical record confirmation, inform the
client that the assessment of his/her heritable cancer risk can change
substantially should records later reveal fewer, greater, or different
cancer diagnoses than reported. Also, because cancer genetic risk
assessment is a dynamic process, a person´s estimated cancer risk can
change if additional relatives are diagnosed with cancer. Therefore,
encourage individuals undergoing cancer genetic risk assessment to
report any changes in their family history.

Document on the pedigree and/or in the clinical summary any pertinent
information obtained through medical record review. Record information
from relatives´ medical records in a manner that attempts to maintain
confidentiality.

**Psychosocial Assessment**

An individual´s decision to seek and utilize information regarding
cancer genetics is based on a variety of factors. Assessment of
psychosocial issues is the optimal method for the clinician to
appreciate all of the factors that affect risk perception and
ultimately, utilization of cancer genetic information. This process can
also enlighten the provider on the potential impact of cancer genetic
information on the client´s quality of life, educational and career
goals, reproductive options, and other life choices. Psychosocial issues
in cancer genetic counseling can be identified and addressed by
integrating the principles and practices of genetic counseling,
psychology, and psycho-oncology into the evaluation.

*Assessing Perception of Risk*

A variety of information is collected to assess the client´s perceived
estimate of personal cancer risk and the methods by which decisions are
made. Such information may include but is not limited to the following:

1.  Motivations for seeking a cancer risk consultation. Clarify the
    client´s goals for the consultation by determining what information
    she/he hopes to gain and guide the session based on those goals.

2.  Beliefs about cancer etiology and perception of risk. Recognizing
    and addressing client beliefs about cancer etiology and risk is a
    critical component of educating and assisting the client in his/her
    adaptation to new cancer risk information.

3.  Ethnocultural information. Awareness of the cultural background,
    religion, and ethnicity of the client can provide deeper
    understanding of how the individual may perceive and utilize the
    information.

4.  Socioeconomic and demographic information. Knowing the client´s age,
    education, occupation, and so forth assists in targeting the
    appropriate degree of genetics information provided and helps to set
    the tone of the counseling session.

5.  Psychosocial factors. Consider referral for additional mental
    health. Identify emotional reactions to cancer risk, such as
    feelings of anger, fear, and guilt, that may provide clues as to how
    the client and/or his/her family will cope with genetic information.
    Be aware that clients with increased levels of distress might not
    comprehend or cope with information as well as less distressed
    clients. Consider referral for additional mental health services
    when the client is having significant difficulty adjusting to
    personal circumstances or in the presence of symptoms related to a
    psychiatric condition. Examples might include prolonged or
    unresolved grief, unrealistic expectations, affective disorder, and
    cancer obsession, among others. Suggest that the client bring a
    support person (spouse, relative, friend) to their cancer genetic
    risk assessment sessions.

6.  Cancer screening. Collect information about the client´s current
    screening practices and ascertain whether there are potential
    compliance issues.

7.  Health behaviors. Identify the client´s perceptions about available
    preventive or risk-reducing therapies such as prophylactic surgery
    or chemoprevention. Prior to genetic testing, determine if the
    client anticipates that cancer genetic information will alter
    his/her health behaviors or decision to take part in risk-reduction
    strategies. Identify barriers to recommended health behaviors and
    explore methods to promote compliance.

8.  Coping strategies. Assess the client´s coping mechanisms, support
    systems, and cancer experiences.

*Process of Psychosocial Assessment*

The format of cancer genetic counseling is interactive and allows time
for information gathering and dissemination. This is best achieved in a
face-to-face consultation to permit assessment of both the client´s
verbal and nonverbal cues. A comprehensive consultation may take place
over several sessions. Genetic counselors often use Carl Rogers´
client-centered approach in eliciting information from patients.
Professionals performing cancer risk counseling require proficient
skills in communication, critical thinking, counseling, and psychosocial
assessment. In addition, they adhere to professional codes of ethics and
values.

Questionnaires and standard psychological measures can provide helpful
information about demographics, family history, screening practices, and
the client´s psychological status. These may be sent to clients prior to
their consultation, filled out at the time of the appointment, or, when
relevant, completed over time (i.e., to monitor screening practices
and/or psychological distress). Written or telephone correspondence are
also ways of gathering psychological and other information.

**Cancer Risk Assessment**

*The Concept of Risk*

*Absolute risk*, which is defined as the probability that an event will
occur (e.g., developing a disease) over a defined period of time, is the
most beneficial way to present cancer risk information in cancer genetic
counseling. Age-specific *lifetime risk* estimates are often most
applicable for medical decision making. For example, a woman may have a
cumulative 30% lifetime risk of breast cancer, but only have a 5% chance
of developing the disease in the next 5 years. For this reason,
*interval risks*, which are lifetime risks divided into defined age
intervals, may be helpful for communicating immediate versus long-range
risks. Such distinctions may have bearing on screening and other cancer
risk management decisions that may depend on which decade of life cancer
risks are most salient. Most epidemiological studies provide relative
risks versus absolute risks. *Relative risks* compare the incidence of
disease in people who have a certain risk factor, like family history,
to those who do not have the risk factor (control group). An *odds
ratio* is an approximation of relative risk derived from case-control
studies. To generate an absolute risk from a relative risk or odds
ratio, it is necessary to know the expected incidence of the disease in
question in the population. For instance, if the incidence of cancer X
in the general population without risk factor A were 1 in 1,000, a
relative risk of 2.0 would mean an absolute risk of 2 in 1,000 (0.2%) in
those with risk factor A. Because the specific incidence due to a
particular risk factor is often not known, relative risks/odd ratios are
often of limited value in counseling patients.

*Conveying Risk Information*

During genetic counseling, clients may be presented with several risk
estimates including the risk for developing specific types of cancer and
the likelihood that they have a genetic mutation associated with cancer
risk. Personal experience may significantly affect the way a client
interprets a numerical risk. Presenting risk information in multiple
ways, such as a percentage and fraction, is helpful. As risk data often
differs between studies, presenting information as ranges is often
useful. It is also important to discuss the chance of never developing
the cancer in question. It may be useful to establish a context for the
risk estimate by pointing out how their heritable cancer risk compares
to cancer risks in the general population. In addition, assessment of
the potential impact of the risk estimate on the client´s health
behavior is indicated.

Assessment of the client´s perception of risk and beliefs about cancer
etiology is done before presenting numerical risk information. Once the
information is presented, verbal and nonverbal cues are used to assess
the patient´s understanding and acceptance.

*Determining Cancer Risk*

In cancer risk assessment, there are two aspects of risk. One is the
absolute risk that the client will develop a specific type of cancer or
cancers based on the family history. The second is the risk that the
client carries a heritable or germline mutation in a cancer
susceptibility gene. Obtaining the genetic pedigree with medical record
confirmation of cancer diagnoses is an obligatory step in accomplishing
both aspects of risk assessment. Once the pedigree is procured, the next
step is to attempt to classify the history as hereditary, familial, or
sporadic.

1.  *Hereditary cancer*. Several excellent resources review the clinical
    features of various hereditary cancer syndromes to help the
    clinician identify at-risk families (see the original guideline
    document for suggested resources). Accurate syndrome identification
    is necessary to determine what types of tumors may occur in
    relatives, the magnitude of risk, and what gene is most likely to be
    involved. Even in the absence of an identifiable syndrome, any
    pedigree that demonstrates autosomal dominant transmission of a
    specific type(s) of cancer is suggestive of an inherited cancer
    predisposition. In families with known syndromes or dominant
    inheritance, first-degree relatives of affected individuals have a
    50% risk of inheriting the putative cancer-predisposing gene
    mutation segregating in the family. Those who do not inherit the
    familial mutation are typically at the general population risk of
    cancer. Those who inherit the mutation are at increased risk of
    developing the associated cancers and for passing the causative gene
    to offspring. Most hereditary cancer syndromes are characterized by
    incomplete penetrance and variable expressivity. Therefore,
    identification of a heritable cancer susceptibility mutation
    generally indicates a probability that cancer will develop but not a
    certainty (incomplete penetrance). Furthermore, age of onset, number
    of primary tumors, and tumor site can vary within and among families
    (variable expressivity).

    a.  Determining absolute cancer risk in hereditary syndromes. Cancer
        risk information is available for many of the defined cancer
        syndromes, such as hereditary breast ovarian cancer syndrome and
        hereditary nonpolyposis colorectal cancer syndrome. Using
        pedigree assessment to determine the likelihood that a client
        has inherited a mutation in a particular cancer-predisposing
        gene and data from the literature regarding cancer risk in
        mutation carriers, it is often possible to estimate a client´s
        heritable cancer risk. It is critical to utilize current risk
        estimates from peer-reviewed research as these numbers have
        changed as understanding of the conditions has increased. If
        there is an identifiable mutation in the family, molecular
        testing can determine definitively whether a person inherited
        the familial mutation and can refine cancer risk estimation. In
        families with autosomal dominant transmission of a specific type
        of cancer without molecular evidence of an identifiable
        syndrome, cancer risk estimation is provided through pedigree
        assessment and the use of available empiric risk models
        (described below).

> In families with known cancer syndromes, Bayes´ theorem can be used to
> refine risk estimates as long as age-specific expression information
> is available for the syndrome in question. For example, relatives who
> have lived beyond the age at which they would likely have developed
> cancer if they had a mutation have a lower chance of actually carrying
> the mutation than is predicted by their position in the pedigree.

b.  Determining the probability of identifying a mutation in hereditary
    cancer families. Models for determining the probability that genetic
    testing will reveal a mutation in a predisposition gene are
    currently available for the BRCA1, BRCA2, MLH1, and MSH2 genes.
    These models utilize factors such as age of onset of cancer, number
    of affected relatives, and presence/absence of associated
    malignancies in estimating the likelihood of a mutation in an
    affected member of the family. Ancestry may also affect the
    likelihood of a mutation in a family, as is the case for BRCA1/2
    mutations in Ashkenazi individuals. Once these models have been
    utilized in a family, pedigree analysis can then determine the
    likelihood that an unaffected relative will have an identifiable
    mutation. Knowing the probability that genetic testing will reveal a
    mutation is helpful for those considering molecular analysis, as
    many clients will have overestimated their risk. It is an important
    component of informed decision-making.

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2.  *Familial cancer*. Histories classified as familial are those in
    which there are more cases of a specific type(s) of cancer than
    expected on the basis of chance alone, but not necessarily
    exhibiting the classic features of hereditary cancers (early age of
    onset, multifocal tumors, dominant inheritance). These histories may
    be the result of small family size, paucity of individuals of the
    higher risk gender, multifactorial influences, chance clustering of
    sporadic cases, underreporting of cancer history in a hereditary
    cancer family, a cancer syndrome with reduced penetrance, or a
    chance limited transmission of a cancer susceptibility gene. Genetic
    testing is often less likely to provide additional information about
    cancer risk in these cases than in hereditary ones.

    a.  Determining absolute cancer risk in familial cases. Statistical
        models are available for estimating cancer risk in familial
        cases of breast cancer and, to a more limited extent, colon,
        ovarian, and prostate cancer (see Table V in original document).
        These models take into account factors such as age of onset,
        number of affected relatives, and the degree of relationship
        between the patient and the affected relatives in estimating
        lifetime cancer risks. One model, the Gail model, takes into
        account specific environmental risk factors but incorporates
        only limited family history information. The risks generated
        from such models are empiric, that is, an estimate based on
        average risk in a population of people with similar risk
        factors. For individuals whose relatives have sporadic cancer,
        the empiric risk calculated by the Gail model may be an
        overestimate of actual cancer risk. In individuals whose
        relatives have hereditary cancer, the empiric risk may be an
        underestimate of actual risk.

> Empiric risks are useful because they can demonstrate to clients that
> not everyone with a family history of cancer is at significantly
> increased risk of developing the disease. In addition, this
> information can be useful to clinicians in deciding how often to
> perform cancer screening and what interventions to offer, if any, to
> reduce cancer risk.

b.  Determining the probability of identifying a mutation in familial
    cancer families. The models mentioned previously can be used to
    determine the likelihood of a heritable mutation in presumed
    familial histories. Reviewing these probabilities with clients
    provides them with statistical evidence as to why testing for
    mutations in hereditary cancer genes may have a low likelihood of
    further characterizing their cancer risk.

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3.  *Sporadic cancer*. Sporadic histories are those in which the
    cancer(s) in the family is mainly due to nonhereditary causes. When
    available, empiric risk data will further support this assessment.
    The likelihood that molecular testing will reveal a mutation in
    families such as these generally approaches the frequency in the
    general population. The exception lies with some rare tumors. For
    instance, up to 10% of patients with \"sporadic\" medullary thyroid
    cancers may have germline mutations in the RET proto-oncogene, which
    causes multiple endocrine neoplasia type. In addition, up to one
    third of cerebellar hemangioblastomas are associated with the
    hereditary cancer syndrome, von Hippel--Lindau. Consequently, be
    aware of the rare tumors that have a significant a priori likelihood
    of being hereditary before ruling out the possibility of increased
    risk to other relatives (see Table II in original document).

4.  *Histories of uncertain significance*. Many families presenting for
    cancer risk assessment have some of the features of an inherited
    syndrome, such as early age of onset, but without clear evidence of
    single gene inheritance. Several factors can lead to difficulty in
    pedigree assessment, including small family size, reduced penetrance
    (lower cancer rates than usual in mutation carriers), a paucity of
    susceptible gender for sex-influenced or sex-limited cancers like
    prostate or breast cancer, prophylactic surgeries in at-risk
    members, and lack of information/inaccurate information regarding
    key relatives in the pedigree, as can be the case with adoption.
    When available, providing empiric estimates of cancer risk and
    mutation probabilities can be useful in such families. Encourage
    families with histories of uncertain significance to report any new
    cancer diagnoses so that the pedigree can be reassessed in the
    future.

> Given the potential complexity of pedigree interpretation, some
> centers have established multidisciplinary case review conferences,
> where pedigrees can be discussed and assessed for clues about possible
> inherited susceptibility. The multidisciplinary format can also
> facilitate discussion of the appropriate cancer risk management
> strategies.

**Molecular Testing for Hereditary Cancer Syndromes**

Consider offering molecular testing for hereditary cancer susceptibility
only when a client has a significant personal and/or family history of
cancer as previously described, the test can be adequately interpreted,
the results will affect medical management, the clinician can provide or
make available adequate genetic education and counseling, and the client
can provide informed consent. With regard to BRCA gene testing
specifically, an updated American Society of Clinical Oncology (ASCO)
statement recommends evaluation by a health care professional
experienced in cancer genetics to determine the appropriateness of
genetic testing. A previous recommendation to offer genetic testing only
if the client has a greater than 10% prior probability of carrying a
mutation has been deleted in 2003 by ASCO. American College of Medical
Genetics (ACMG) Foundation, in their 1999 document \"Genetic
Susceptibility to Breast and Ovarian Cancer: Assessment, Counseling, and
Testing Guidelines\" does not establish a numerical cutoff for when
cancer genetic testing should or should not be offered. However, the
guideline states that testing is not recommended in situations where
there is a low probability of carrying a mutation, given the financial
cost of cancer genetic testing as well as the potential psychological
ramifications. Furthermore, the ACMG states that to offer genetic
testing is to take the responsibility, either personally or through
referral to appropriate professionals, for adequate pretest education,
the process of informed consent, and posttest counseling.

*Regulation of Genetic Testing*

1.  *Clinical testing*. Molecular analysis is available on a clinical,
    fee-for-service basis, for an increasing number of genes implicated
    in hereditary cancer syndromes. The Clinical Laboratory Improvement
    Act (CLIA) establishes standards for these clinical testing
    laboratories. Medicare and many third-party insurance carriers
    require CLIA certification for reimbursement of molecular analysis.
    For this reason, as well as for quality control, clinical genetic
    tests should be ordered from CLIA-approved laboratories.

2.  *Research testing*. Molecular analysis may be available within the
    context of a research study. Such studies must have an
    institutional-review-board-approved protocol and a written informed
    consent form that research participants are required to sign.

When both clinical and research testing are available to a client, the
pros and cons of each approach should be discussed in detail. Unlike
clinical laboratories, research laboratories do not have to be
CLIA-approved. Therefore, the research laboratory may not be able to
release results to the client unless a CLIA-approved laboratory confirms
them. The turnaround time for results, if and when they are released, is
generally longer for research versus clinical tests. However, a
potential benefit of research testing is that tests are performed at
reduced or no cost.

*Pretest Genetic Counseling and Informed Consent*

Prior to beginning an in-depth discussion of the benefits, risks, and
limitations of genetic testing, inquire about the client´s motivations
and expectations for pursuing cancer genetic testing.

Informed consent is a necessary component of molecular testing for
hereditary cancer syndromes whether in a clinical or research setting.
The process of informed consent includes a thorough discussion of the
possible outcomes of testing, a review of the possible benefits, risks,
and limitations, and a discussion of alternatives to molecular testing.
Basic elements of informed consent in cancer genetic risk assessment and
genetic counseling have been reviewed in the medical literature and are
described below. In general, genetic cancer susceptibility testing is
not performed on persons under the age of 18, as minors may not be able
to give informed consent. The exception includes cases where medical
intervention is warranted in childhood such as with familial adenomatous
polyposis (*APC* testing) and multiple endocrine neoplasia type II
(*RET* testing).

*Elements of Informed Consent for Cancer Genetic Testing*

1.  *Purpose of the test and who to test*. Explain why the test is being
    offered, if and how the results might alter the client´s cancer
    risk, and how the results might affect medical management. For
    clients who are seeking presymptomatic genetic testing, in the
    absence of a known mutation in their family, discuss the importance
    of testing an affected relative first. This approach helps determine
    whether there is an identifiable mutation in the gene(s) in question
    for which unaffected relatives can be tested. The best relative with
    whom to initiate genetic testing is generally one who had an early
    age of onset of the cancer in question and/or multifocal cancer. In
    some cases, an affected relative may not be available (deceased or
    out of contact with the family), willing, or financially able to
    proceed with testing. In such situations, discuss the limitations of
    presymptomatic testing without an identified mutation in detail with
    the client (see below).

2.  *General information about the gene(s)*. Review cancer risks
    associated with gene mutations including the concepts of penetrance
    and variable expressivity and the possibility of genetic
    heterogeneity.

3.  *Possible test results*. Explain the implications of all possible
    test results and the likelihood that the test will be informative.

    a.  *Positive result: A functionally significant mutation that
        indicates an increased cancer risk*. The likelihood of
        developing various cancers depends upon the gene in which the
        mutation is detected and sometimes where in the gene the
        mutation is located. Epigenetic factors (other genes and
        environmental risk factors) may also modify cancer risk. In the
        case of presymptomatic testing, results indicate a probability
        of developing cancer, not a certainty, and do not indicate when
        cancer may develop or the tumor site.

    b.  *Negative result: No mutation identified*. In the absence of a
        known mutation in a family, a negative result in an unaffected
        person with a strong family history of cancer is generally
        considered uninformative. The family may have a mutation in the
        gene tested that is not detectable with current technology.
        Alternatively, because many cancer syndromes are genetically
        heterogeneous, the family may carry a mutation in a different
        gene. It is important to stress the nature of an uninformative
        negative test result in this setting. Failure to understand the
        significance of an uninformative negative result may lead to
        failure to comply with recommended cancer screening or cancer
        risk reduction practices. The interpretation of the significance
        of a negative result in an affected person depends on the
        sensitivity of the genetic test, the family history, and the a
        priori likelihood that the individual would have had a positive
        result.

    c.  *Negative result: Known mutation in family*. If a functionally
        significant mutation has been previously identified in a close
        biological relative and the client tests negative for the
        mutation, he/she is not at increased risk of developing cancer
        based on the family history and is instead at general population
        risk. Testing the client for the familial mutation only is
        usually sufficient. An exception may be the cases where the
        client belongs to an ethnic group in which common, recurrent
        mutations have been identified. For instance, in Ashkenazi
        families that carry one of the three common *BRCA1/2* mutations,
        relatives electing to have molecular analysis should be tested
        for all three mutations, not just the one identified in the
        family

    d.  *Variant of uncertain significance: An alteration in a gene has
        been identified but it is unknown whether the alteration will
        affect gene function*. Examples of variants of unknown
        significance can include missense mutations of unknown
        functional significance or alterations in intronic sequences not
        known to be involved with messenger ribonucleic acid (mRNA)
        processing. Further studies involving the client and his/her
        relatives as well as an improved understanding of gene function
        may be necessary to establish the clinical significance of a
        variant. Unless the variant is determined to be significant
        (i.e., affecting gene function), predictive genetic testing
        cannot be performed in other relatives. If significant family
        history is present, such a result does not rule out a hereditary
        cancer syndrome in the family, and appropriate medical
        management should be based on family history alone.

4.  *Likelihood of positive result*. When available, use statistical
    models, pedigree assessment, and/or Bayes´ theorem to provide the
    client with information about the chance that testing will reveal a
    mutation in the gene(s) in question. Provide clients with
    qualitative and/or quantitative information about the likelihood of
    a positive rest result (see the section Determining the probability
    of identifying a mutation in hereditary cancer families).

5.  *Technical aspects and accuracy of the test*. Review method(s) that
    will be used for mutational analysis and the likelihood of a
    false-positive or false-negative result (sensitivity and
    specificity).

6.  *Economic considerations*. Apprise the client of the cost of genetic
    testing and that some insurance plans may not provide reimbursement
    for such tests. Because of the high costs of many genetic tests, it
    may be useful to determine insurance coverage before proceeding.
    Inform the client of the benefits and risks associated with pursuing
    reimbursement for a genetic test (see below).

7.  *Risks of genetic discrimination*. Persons considering genetic
    testing for cancer susceptibility need to be aware of (1) the
    potential consequences on insurability, (2) whether the results will
    be disclosed to any third party (including the referring physician),
    and (3) whether the center initiating the testing has any
    confidentiality safeguards. Encourage clients to review their
    insurance policies prior to testing.

> Inform clients about the status and limitations of state and federal
> legislation providing protection against genetic discrimination in
> health insurance, life insurance, and employability. At the federal
> level, the Health Insurance Portability and Accountability Act (HIPAA)
> of 1996 provides some protection against genetic discrimination with
> regard to health insurance for individuals with group policies
> (<http://www.hhs.gov/ocr/hipaa/>). Information about genetic
> discrimination, current legislation, and bills up for consideration
> can be found at the following websites:
> [http://thomas.loc.gov](http://thomas.loc.gov/), and
> <http://www.nationalpartnership.org/>. In addition, be familiar with
> the current legislation in your state to be able to explain the
> protections or lack of protections it affords clients seeking genetic
> testing (see
> <http://www.genome.gov/PolicyEthics/LegDatabase/pubsearch.cfm>).
>
> Life and disability insurance are generally considered separately from
> health insurance. Some life/disability insurers now include questions
> regarding genetic testing on the application form. Persons who do not
> already have life/disability insurance at the time they are tested may
> jeopardize their chances of obtaining such policies if they are found
> to have a gene mutation.
>
> The possibility of employment discrimination was addressed in 1995
> when the Equal Employment Opportunity Commission (EEOC) issued a
> guideline interpreting the Americans with Disabilities Act (ADA) to
> prohibit workplace discrimination of healthy persons based on genetic
> tests.

8.  *Psychosocial aspects*. The components of psychosocial assessment
    regarding testing to be addressed include but are not limited to the
    following:

    a.  *Anticipated reaction to results*. Discuss with the client
        his/her anticipated reactions to positive, negative,
        uninformative, or ambiguous results, and explore anticipated
        coping strategies. Failure to anticipate reactions accurately
        can lead to increased emotional distress months after testing.

    b.  *Timing and readiness for testing*. Ascertain the client´s
        readiness to proceed with testing and reassure him/her that
        testing can be performed at a later date if preferable. Discuss
        the option of deoxyribonucleic acid (DNA) banking when
        applicable.

    c.  *Family issues*. Explore whether the client has discussed
        testing with his/her spouse or partner and family members, their
        reactions to obtaining genetic information, and how their
        reactions might influence relationships with the client. Discuss
        client´s plans for sharing results.

    d.  *Preparing for results*. Prepare the client for how results will
        be provided. Discuss who will be present at the session, the
        language used to share results, and what will happen following
        the results session. Refer to mental health professional if
        indicated.

9.  *Confidentiality issues*. Prior to testing, discuss confidentiality
    with the client as it pertains to how or if information will be
    released to his/her insurer, referring physician, and other family
    members.

10. *Utilization of test results: medical surveillance and preventative
    measures*. Review recommendations for cancer screening, available
    preventive measures, and the limitations of such approaches. Discuss
    how or if these recommendations would change in the event of a
    negative versus positive genetic test result. Ascertain how the
    client anticipates test results will affect his/her medical
    management and health behaviors.

11. *Alternatives to genetic testing*. Review methods of cancer risk
    estimation and options for medical management in the absence of
    genetic testing. Not all family members will choose genetic testing
    as an appropriate option. Discuss the availability of DNA banking.

12. *Storage and potential reuse of genetic material*. Inform the client
    of the testing laboratory´s policy for storage or potential reuse of
    genetic material.

*Sample Collection*

If or when a client has decided to proceed with molecular testing,
coordinate sample collection and shipment. Provide the client with an
estimated turnaround time for completion of genetic test results and
establish a plan for disclosing results. Encourage the client to bring a
support person to the results disclosure session. Inform the client that
he/she has the option to withdraw from the testing process or delay
results disclosure.

*Results Disclosure and Post-test Counseling*

This is a multi-step process, optimally done during a face-to-face
meeting.

1.  *Results disclosure*. After client´s consent, inform him/her of the
    result.

2.  *Significance of test results*. Review the specificity and
    sensitivity of the test and discuss how the client´s result affects
    his/her cancer risk.

3.  *Impact of test results*. Assess the emotional impact of the result
    on the client and his/her support person through verbal and
    nonverbal cues; provide support as needed.

4.  *Medical management*. Review screening recommendations and options
    of cancer risk reduction, such as chemoprevention or prophylactic
    surgery, if available, including benefits, risks, and limitations of
    these options. Provide referrals to other medical professionals for
    additional discussions of these topics and strongly encourage
    compliance with screening recommendations.

5.  *Informing other relatives*. Discuss cancer risks to other relatives
    and importance of informing family members about family
    history/genetic test results. Written documentation that the client
    can share with relatives may be provided, safeguarding
    confidentiality as desired by client. If a high-risk client refuses
    to contact at-risk relatives, an ethics consult is an option

6.  *Future contact*. If follow-up care will be managed elsewhere,
    encourage the client to maintain contact with the cancer risk
    assessment center for updates about their family history, the
    genetics of familial cancer disorders, and the management of
    inherited predisposition to cancer. The same applies to high-risk
    families with negative test results who may be candidates for future
    genetic tests. When available, offer clients the option of
    participating in long-term follow-up studies.

7.  *Resources*. Provide the client with resources about cancer genetics
    (see Table VI in the original guideline document) and contacts with
    other willing clients, if desired and available. Serve as a
    psychosocial support resource for the client or refer to other
    qualified individuals if additional support is needed.

**Surveillance/Treatment/Follow-Up**

Follow-up for all clients seeking cancer genetic risk assessment and
genetic counseling services, regardless of cancer risk category, should
include a discussion of cancer screening guidelines, reviewing
limitations when relevant, methods for reducing cancer risk if known,
and referrals to appropriate medical professionals for long-term medical
management if needed.

**Summary**

Cancer genetic risk assessment and genetic counseling is a multistep
process. The process begins by collecting information about the client´s
personal medical history and family history to assess heritable cancer
risk. A psychosocial assessment is also performed to determine the
client´s perception of risk and ability to cope with risk information.
Once this information is collected, a counseling model is used to
discuss risk, facilitate adjustment to risk, provide informed consent
for genetic testing when applicable, and review options for medical
management. Genetic counseling is an integral part of cancer genetic
risk assessment that enhances clients´ ability to cope with and
understand the genetic information presented.

**Special Cases/Exceptions to Practice Recommendations**

*Genetic testing of at-risk individuals during childhood*: Because
minors may not be able to give informed consent, in general, genetic
cancer susceptibility testing is not performed on persons under the age
of 18 years. The exception includes cases where medical intervention is
warranted in childhood such as with familial adenomatous polyposis
(*APC* testing) and multiple endocrine neoplasia type II (*RET*
testing).

*Adopted proband*: Individuals with early-onset cancer who have no
details regarding family history will be evaluated on the basis of
personal medical and psychosocial history alone.

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

All supporting evidence is class III, opinions of respected authorities,
based on clinical experience, descriptive studies, or reports of expert
committees. No supporting literature of categories I and II was
identified.

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

-   Early detection of heritable cancers

-   Prevention of heritable cancers by alerting at-risk individuals to
    make appropriate lifestyle or environmental changes

#### POTENTIAL HARMS

-   Economic considerations

-   High costs of many genetic tests

-   Uncertainty of insurance reimbursement

-   Risks of genetic discrimination.

-   Potential consequences on insurability

-   Risk of unwanted third party disclosure

-   Potential for confidentiality breach

-   Possibility of illegal employment discrimination

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

The genetic counseling recommendations of the National Society of
Genetic Counselors (NSGC) are developed by members of the NSGC to assist
practitioners and patients in making decisions about appropriate
management of genetic concerns. Each practice recommendation focuses on
a clinical or practice issue and is based on a review and analysis of
the professional literature. The information and recommendations reflect
scientific and clinical knowledge current as of the submission date and
are subject to change as advances in diagnostic techniques, treatments,
and psychosocial understanding emerge. In addition, variations in
practice, taking into account the needs of the individual patient and
the resources and limitations unique to the institution or type of
practice, may warrant approaches, treatments, or procedures alternative
to the recommendations outlined in this document. Therefore, these
recommendations should not be construed as dictating an exclusive course
of management, nor does use of such recommendations guarantee a
particular outcome. Genetic counseling recommendations are never
intended to displace a health care provider´s best medical judgment
based on the clinical circumstances of a particular patient.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Staying Healthy

#### IOM DOMAIN

Patient-centeredness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Trepanier A, Ahrens M, McKinnon W, Peters J, Stopfer J, Grumet SC,
Manley S, Culver JO, Acton R, Larsen-Haidle J, Correia LA, Bennett R,
Pettersen B, Ferlita TD, Costalas JW, Hunt K, Donlon S, Skrzynia C,
Farrell C, Callif-Daley F, Vockley CW. Genetic cancer risk assessment
and counseling: recommendations of the National Society of Genetic
Counselors. J Genet Counsel 2004 Apr;13(2):83-114. \[104 references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15604628)

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2004 Apr

#### GUIDELINE DEVELOPER(S)

National Society of Genetic Counselors - Medical Specialty Society

#### SOURCE(S) OF FUNDING

This project was supported by the National Society of Genetic
Counselors, Inc.

#### GUIDELINE COMMITTEE

Genetic Services Committee of the National Society of Genetic Counselors

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Primary authors*: Angela Trepanier, Center for Molecular Medicine and
Genetics, Wayne State University School of Medicine, Wayne State
University, Detroit, Michigan; Mary Ahrens, Fairview University Medical
Center, University of Minnesota, Minneapolis, Minnesota; Wendy McKinnon,
Vermont Regional Genetics Center, Familial Cancer Program, Burlington,
Vermont; June Peters, Cancer Genetics Branch, Division of Cancer
Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health, Department of Health and Human Services,
Rockville, Maryland; Jill Stopfer, Cancer Risk Evaluations Program,
Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania;
Sherry Campbell Grumet, Cancer Risk Assessment Counseling Program,
Englewood-Mount Sinai, Englewood, New Jersey; Susan Manley, Myriad
Genetics Laboratories, Inc., Salt Lake City, Utah; Julie O. Culver, Fred
Hutchinson Cancer Research Center, Seattle, Washington; Ronald Acton,
University of Alabama at Birmingham, Birmingham, Alabama; Joy
Larsen-Haidle, University of Iowa, Iowa City, Iowa; Lori Ann Correia,
V.I. Technologies, Inc., Watertown, Massachusetts; Robin Bennett,
Division of Medical Genetics, University of Washington Medical Center,
Seattle, Washington; Barbara Pettersen, Genetic Counseling of Central
Oregon, Bend, Oregon; Terri Diamond Ferlita, Myriad Genetics
Laboratories, Inc., Salt Lake City, Utah; Josephine Wagner Costalas, Fox
Chase Cancer Center, Philadelphia, Pennsylvania; Katherine Hunt,
University Hospital of New Mexico, University of New Mexico Health
Sciences Center, Albuquerque, New Mexico; Susan Donlon, Queen´s
Comprehensive Genetics Center, Honolulu, Hawaii; Cecile Skrzynia,
Department of Medicine, University of North Carolina, Chapel Hill, North
Carolina; Carolyn Farrell, Roswell Park Cancer Center, Buffalo, New
York; Faith Callif-Daley, Children´s Medical Center, Dayton, Ohio;
Catherine Walsh Vockley, Familial Cancer Program, Department of Medical
Genetics, Mayo Clinic, Rochester, Minnesota

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Not stated

#### GUIDELINE STATUS

This is the current release of the guideline.

#### GUIDELINE AVAILABILITY

Electronic copies: Not available at this time.

Print copies: Available from the National Society of Genetic Counselors,
233 Canterbury Drive, Wallingford, PA 19086-7608; Web site:
[www.nsgc.org](http://www.nsgc.org/).

#### AVAILABILITY OF COMPANION DOCUMENTS

None available

#### PATIENT RESOURCES

None available

#### NGC STATUS

This NGC summary was completed by ECRI on September 21, 2004. The
information was verified by the guideline developer on September 23,
2004.

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is subject to
the guideline developer\'s copyright restrictions.

### DISCLAIMER

#### NGC DISCLAIMER

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Date Modified: 11/10/2008