Genetic Counseling

Genetic Counseling

Ellen T. Matloff

Danielle C. Bonadies


Clinically based genetic testing has evolved from an uncommon analysis ordered for the rare hereditary cancer family to a widely available tool ordered on a routine basis to assist in surgical and radiation decision making, chemoprevention, and surveillance of the patient with cancer, as well as management of the entire family. The evolution of this field has created a need for accurate cancer genetic counseling and risk assessment. Extensive coverage of this topic by the media, including Angelina Jolie’s public disclosure of her BRCA1+ status in May 2013, and widespread advertising by commercial testing laboratories have further fueled the demand for counseling and testing.

Cancer genetic counseling is a communication process between a health-care professional and an individual concerning cancer occurrence and risk in his or her family.1 The process, which may include the entire family through a blend of genetic, medical, and psychosocial assessments and interventions, has been described as a bridge between the fields of traditional oncology and genetic counseling.1

The goals of this process include providing the client with an assessment of individual cancer risk, while offering the emotional support needed to understand and cope with this information. It also involves deciphering whether the cancers in a family are likely to be caused by a mutation in a cancer gene and, if so, which one. There are >30 hereditary cancer syndromes, many of which can be caused by mutations in different genes. Therefore, testing for these syndromes can be complicated. Advertisements by genetic testing companies bill genetic testing as a simple process that can be carried out by health-care professionals with no training in this area; however, there are many genes involved in cancer, the interpretation of the test results is often complicated, the risk of result misinterpretation is great and associated with potential liability, and the emotional and psychological ramifications for the patient and family can be powerful.2,3 A few hours of training by a company generating a profit from the sale of these tests does not adequately prepare providers to offer their own genetic counseling and testing services.4 Furthermore, the delegation of genetic testing responsibilities to office staff and, recently, mammography technicians, is alarming and likely presents a huge liability for these ordering physicians, their practices, and their institutions.5,6 Providers should proceed with caution before taking on the role of primary genetic counselor for their patients.

Counseling about hereditary cancers differs from traditional genetic counseling in several ways. Clients seeking cancer genetic counseling are rarely concerned with reproductive decisions, which are often the primary focus in traditional genetic counseling, but are instead seeking information about their own and other relatives’ chances of developing cancer.1 Additionally, the risks given are not absolute but change over time as the family and personal history changes and the patient ages. The risk reduction options available are often radical (e.g., chemoprevention or prophylactic surgery), and are not appropriate for every patient at every age. The surveillance and management plan must be tailored to the patient’s age, childbearing status, menopausal status, risk category, ease of screening, and personal preferences and will likely change over time with the patient. The ultimate goal of cancer genetic counseling is to help the patient reach the decision best suited to her personal situation, needs, and circumstances.

There are now a significant number of referral centers across the country specializing in cancer genetic counseling, and the numbers are growing. However, some experts insist that the only way to keep up with the overwhelming demand for counseling will be to educate more physicians and nurses in cancer genetics. The feasibility of adding another specialized and time-consuming task to the clinical burden of these professionals is questionable, particularly with average patient encounters of 19.5 and 21.6 minutes for general practitioners and gynecologists, respectively.7,8 A more practical goal is to better educate clinicians in the area of risk assessment so that they can screen their patient populations for individuals at high risk for hereditary cancer and refer them on to comprehensive counseling and testing programs. Access to genetic counseling is no longer an issue because there are now internet, phone, and satellite-based telemedicine services available (Table 35.1), with most major health insurance companies now covering these services9,10,11 and several requiring them.12


Only 5% to 10% of most cancer is thought to be caused by single mutations within autosomal-dominant inherited cancer susceptibility genes.13 The key for clinicians is to determine which patients are at greatest risk to carry a hereditary mutation. There are seven critical risk factors in hereditary cancer (Table 35.2). The first is early age of cancer onset. This risk factor, even in the absence of a family history, has been shown to be associated with an increased frequency of germline mutations in many types of cancers.14 The second risk factor is the presence of the same cancer in multiple affected relatives on the same side of the pedigree. These cancers do not need to be of similar histologic type in order to be caused by a single mutation. The third risk factor is the clustering of cancers known to be caused by a single gene mutation in one family (e.g., breast/ovarian/pancreatic cancer or colon/uterine/ovarian cancers). The fourth risk factor is the occurrence of multiple primary cancers in one individual. This includes multiple primary breast or colon cancers as well as a single individual with separate cancers known to be caused by a single gene mutation (e.g., breast and ovarian cancer in a single individual). Ethnicity also plays a role in determining who is at greatest risk to carry a hereditary cancer mutation. Individuals of Jewish ancestry are at increased risk to carry three specific BRCA1/2 mutations.15 The presence of a cancer that presents unusually—in this case, breast cancer in a male—represents a sixth risk factor and is important even when it is the only risk factor present. Finally, the last risk factor is pathology. Certain types of cancer are overrepresented in hereditary cancer families. For example, medullary and triple negative breast
cancers (where the estrogen, progesterone and Her2 receptors are all negative, often abbreviated ER-/PR-/Her2) are overrepresented in BRCA1 families,16,17 and the National Comprehensive Cancer Network (NCCN) BRCA testing guidelines now include individuals diagnosed with a triple negative breast cancer <age 60 years.18 However, breast cancer patients without these pathologic findings are not necessarily at lower risk to carry a mutation. In contrast, patients with a borderline or mucinous ovarian carcinoma are at lower risk to carry a BRCA1 or BRCA2 mutation19 and may instead carry a mutation in a different gene. It is already well-established that medullary thyroid carcinoma, sebaceous adenoma or carcinoma, adrenocortical carcinoma before the age of 25 years, and multiple adenomatous, hamartomatous, or juvenile colon polyps are indicative of other rare hereditary cancer syndromes.11,20 These risk factors should be viewed in the context of the entire family history, and must be weighed in proportion to the number of individuals who have not developed cancer. The risk assessment is often limited in families that are small or have few female relatives; in such families, a single risk factor may carry more weight.

TABLE 35.1 How to Find a Genetic Counselor for Your Patient

American Board of Genetic Counselors

Directory of board-certified genetic counselors


(800) 975-4819

A nationwide network of independent genetic counselors that use telephone and internet technology to bring genetic counseling to patients and providers. Covered by many insurance companies.

National Society of Genetic Counselors (click “Find a Counselor” button)

(312) 321-6834

For a listing of genetic counselors in your area who specialize in cancer.

National Cancer Institute Cancer Genetics Services Directory

(800) 4-CANCER

A free service designed to locate providers of cancer risk counseling and testing services.

TABLE 35.2 Risk Factors that Warrant Genetic Counseling for Hereditary Cancer Syndromes

  1. Early age of onset (e.g., <50 years for breast, colon, and uterine cancer)

  2. Multiple family members on the same side of the pedigree with the same cancer

  3. Clustering of cancers in the family known to be caused by a single gene mutation (e.g., breast/ovarian/pancreatic; colon/uterine/ovarian; colon cancer/polyps/desmoid tumors/osteomas)

  4. Multiple primary cancers in one individual (e.g., breast/ovarian cancer; colon/uterine; synchronous/metachronous colon cancers; <15 gastrointestinal polyps; <5 hamartomatous or juvenile polyps)

  5. Ethnicity (e.g., Jewish ancestry for breast/ovarian cancer syndrome)

  6. Unusual presentation of cancer/tumor (e.g., breast cancer in a male; medullary thyroid cancer; retinoblastoma; even one sebaceous carcinoma or adenoma)

  7. Pathology (e.g., triple negative [ER/PR/Her-2] breast cancer <60; medullary breast cancers are overrepresented in women with hereditary breast and ovarian cancer; a colon tumor with an abnormal microsatellite instability (MSI) or immunohistochemistry (IHC) result increases the risk for a hereditary colon cancer syndrome)

A less common, but extremely important, finding is the presence of unusual physical findings or birth defects that are known to be associated with rare hereditary cancer syndromes. Examples include benign skin findings, autism, large head circumference20,21 and thyroid disorders in Cowden syndrome, odontogenic keratocysts in Gorlin syndrome,22 and desmoid tumors or dental abnormalities in familial adenomatous polyposis (FAP).23 These and other findings should prompt further investigation of the patient’s family history and consideration of a referral to genetic counseling.

In this chapter, the breast/ovarian cancer counseling session with a female patient will serve as a paradigm by which all other sessions may follow broadly.


Precounseling Information

Before coming in for genetic counseling, the counselee should be informed about what to expect at each visit, and what information he/she should collect ahead of time. The counselee can then begin to collect medical and family history information and pathology reports that will be essential for the genetic counseling session.

Family History

An accurate family history is undoubtedly one of the most essential components of the cancer genetic counseling session. Optimally, a family history should include at least three generations; however, patients do not always have this information. For each individual affected with cancer, it is important to document the exact diagnosis, age at diagnosis, treatment strategies, and environmental exposures (i.e., occupational exposures, cigarettes, other agents).24 The current age of the individual, laterality, and occurrence of any other cancers must also be documented. Cancer diagnoses should be confirmed with pathology reports whenever possible. A study by Love et al.25 revealed that individuals accurately reported the primary site of cancer only 83% of the time in their first degree relatives with cancer, and 67% and 60% of the time in second and third degree relatives, respectively. It is common for patients to report a uterine cancer as an ovarian cancer, or a colon polyp as an invasive colorectal cancer. These differences, although seemingly subtle to the patient, can make a tremendous difference in risk assessment. Individuals should be asked if there are any consanguineous (inbred) relationships in the family, if any relatives were born with birth defects or mental retardation, and whether other genetic diseases run in the family (e.g., Fanconi anemia, Cowden syndrome), because these pieces of information could prove to be important in reaching a diagnosis.

The most common misconception in family history taking is that somehow a maternal family history of breast, ovarian, or uterine cancer is more significant than a paternal history. Conversely, many still believe that a paternal history of prostate cancer is more significant than a maternal history. Few cancer genes discovered thus far are located on the sex chromosomes and, therefore, both maternal and paternal history are significant and must be explored thoroughly. It has also become necessary to elicit the spouse’s personal and family history of cancer. This has bearing on
the cancer status of common children, but may also determine if children are at increased risk for a serious recessive genetic disease such as Fanconi anemia.26 Children who inherit two copies of a BRCA2 mutation (one from each parent) are now known to have this serious disorder characterized by defective DNA repair and high rates of birth defects, aplastic anemia, leukemia, and solid tumors.26 Patients should be encouraged to report changes in their family history over time (e.g., new cancer diagnoses, genetic testing results in relatives), because this may change their risk assessment and counseling.

A detailed family history should also include genetic diseases, birth defects, mental retardation, multiple miscarriages, and infant deaths. A history of certain recessive genetic diseases (e.g., ataxia telangiectasia, Fanconi anemia) can indicate that healthy family members who carry just one copy of the genetic mutation may be at increased risk to develop cancer.26,27 Other genetic disorders, such as hereditary hemorrhagic telangiectasia, can be associated with a hereditary cancer syndrome caused by a mutation in the same gene—in this case, juvenile polyposis.28

Dysmorphology Screening

Congenital anomalies, benign tumors, and unusual dermatologic features occur in a large number of hereditary cancer predisposition syndromes. Examples include osteomas of the jaw in FAP, palmar pits in Gorlin syndrome, and papillomas of the lips and mucous membranes in Cowden syndrome. Obtaining an accurate past medical history of benign lesions and birth defects, and screening for such dysmorphology can greatly impact diagnosis, counseling, and testing. For example, BRCA1/2 testing is inappropriate in a patient with breast cancer who has a family history of thyroid cancer and the orocutaneous manifestations of Cowden syndrome.

Risk Assessment

Risk assessment is one of the most complicated components of the genetic counseling session. It is crucial to remember that risk assessment changes over time as the person ages and as the health statuses of their family members change. Risk assessment can be broken down into three separate components.

  • What is the chance that the counselee will develop the cancer observed in his/her family (or a genetically related cancer such as ovarian cancer due to a family history of breast cancer)?

  • What is the chance that the cancers in this family are caused by a single gene mutation?

  • What is the chance that we can identify the gene mutation in this family with our current knowledge and laboratory techniques?

Cancer clustering in a family may be due to genetic and/or environmental factors, or may be coincidental because some cancers are very common in the general population.29 Although inherited factors may be the primary cause of cancers in some families, in others, cancer may develop because an inherited factor increases the individual’s susceptibility to environmental carcinogens. It is also possible that members of the same family may be exposed to similar environmental exposures due to shared geography or patterns in behavior and diet that may increase the risk of cancer.30 Therefore, it is important to distinguish the difference between a familial pattern of cancer (due to environmental factors or chance) and a hereditary pattern of cancer (due to a shared genetic mutation). Emerging research is also evaluating the role and clinical utility of more common low-penetrance susceptibility genes and single nucleotide polymorphisms (SNP) that may account for a proportion of familial cancers.31

Several models are available to calculate the chance that a woman will develop breast cancer, including the Gail and Claus models.32,33 Computer-based models are also available to help determine the chance that a BRCA mutation will be found in a family.34 At first glance, many of these models appear simple and easy to use, and it may be tempting to exclusively rely on these models to assess cancer risk. However, each model has its strengths and weaknesses, and the counselor needs to understand the limitations well and know which are validated, which are considered problematic, when a model will not work on a particular patient, or when another genetic syndrome should be considered. For example, none of the existing models are able to factor in other risks that may be essential in hereditary risk calculation (e.g., a sister who was diagnosed with breast cancer after radiation treatment for Hodgkin disease).

The risk of a detectable mutation will also vary based on cancer history and the degree of relationship to an affected family member. For example, family members with early-onset breast cancer have a higher likelihood of testing positive than unaffected family members. Therefore, the risk assessment process should include a discussion of which family member is the best candidate for testing.

DNA Testing

DNA testing is now available for a variety of hereditary cancer syndromes. However, despite misrepresentation by the media, testing is feasible for only a small percentage of individuals with cancer. DNA testing offers the important advantage of presenting clients with actual risks instead of the empiric risks derived from risk calculation models. DNA testing can be very expensive; full sequencing and rearrangement testing of the BRCA1/2 genes currently averages $2,500, and full panel testing costs up to $7,000 per patient. Importantly, testing should begin in an affected family member whenever possible to maximize scientific accuracy. Most insurance companies now cover cancer genetic testing in families where the test is medically indicated.

One of the most crucial aspects of DNA testing is accurate result ordering and interpretation. Unfortunately, errors in ordering and interpretation are the greatest risk of genetic testing and are very common.35 Emerging data reveal that between 30% to 50% of genetic tests are ordered inappropriately, which is problematic for patients, clinicians, and insurers.36,37,38 Recent data demonstrate that many medical providers have difficulty interpreting even basic pedigrees and genetic test results.33,34,35 Additional studies have demonstrated that an inaccurate interpretation of genetic testing has been shown to result in inappropriate medical management recommendations, unnecessary prophylactic surgeries, a massive waste of health-care dollars, psychosocial distress, and false reassurance for patients.2,3

Interpretations are becoming increasingly complicated as more tests and gene panels become available. For example, one study demonstrated that approximately 25% of high-risk families that were BRCA1 and BRCA2 negative by commercially available sequencing were found to carry a deletion or duplication in one of these genes, or a mutation in another gene.39

This is particularly concerning in an era in which testing companies are canvassing physicians, and now mammography technicians, and encouraging them to perform their own counseling and testing. The potential impact of test results on the patient and his/her family is great and, therefore, accurate interpretation of the results is paramount. Professional groups have recognized this and have adopted standards encouraging clinicians to refer patients to genetics experts to ensure proper ordering and interpretation of genetic tests. The U.S. Preventive Services Task Force recommends that women whose family history is suggestive of a BRCA mutation be referred for genetic counseling before being offered genetic testing.40 The American College of Surgeons’ Commission on Cancer standards include “cancer risk assessment, genetic counseling and testing services provided to patients either on site
or by referral, by a qualified genetics professional.”4 In an effort to reduce errors, some insurance companies are requiring genetic counseling by a certified genetic counselor before testing for hereditary breast or colon cancer syndromes.12

Results can fall into a few broad categories. It is important to note that a negative test result can actually be interpreted in three different ways, detailed in #2, #3, and #4, which follows.

Jun 28, 2016 | Posted by in ONCOLOGY | Comments Off on Genetic Counseling
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