Indications for referral to assess cancer risk
- Individual has first-degree relatives (parents, sisters, brothers, or children) with cancer.
- Individual has two or more relatives on the same side of the family with the same or related cancers, especially those of the breast, ovary, or colon.
- Early-onset cancer in patient or relative, such as breast, ovarian, or colon cancer before the age of 50.
- Primary cancers in bilateral organs in patient or relative.
- Two different primary cancers in patient or relative, such as primary breast and ovarian cancers or primary colon and uterine cancers.
- Rare cancer type in patient or relative, such as male breast cancer, medullary thyroid cancer, paraganglioma, retinoblastoma, or sarcoma.
- Inherited syndromes that predispose toward cancer in a person or relative, such as multiple intestinal polyposis, neurofibromatosis, or Cowden disease.
- A known cancer-predisposing genetic mutation in the family.
Reasons for seeking cancer risk assessment
- Seeking intensive medical screening.
- Wanting information on prophylactic surgery.
- Considering DNA testing.
- Wanting to discuss risk of cancer.
- Seeking advice on lifestyle modification.
- Wanting to determine if already diagnosed cancer is associated with inherited predisposition.
- Interested in discussing risk of cancer in offspring/other family members.
Cancer risk consultation
The Cancer Genetics Program offers a broad range of diagnostic tools to identify increased cancer risk. Assessments may be performed both when genetic testing is unavailable and when a person elects to forego testing, using epidemiological models and computer algorithms. Cancer risk specialists, the individual, and his or her personal physician develop an individualized cancer surveillance and preventive strategy.
The family history of cancer is a necessary first step in identifying appropriate individuals and families for laboratory analysis, as particular cancer types, ages of onset, and patterns of inheritance are associated with mutations in specific genes.
Cancer risk assessment can provide accurate cancer risk information and cancer-screening guidelines. It can also determine the availability and appropriateness of genetic testing for cancer predisposition.
Most insurance companies cover genetic consultation fees and genetic testing. The risk of genetic discrimination seems minimal, and laws have been enacted to protect against health insurance discrimination.
Genetic testing for cancer predisposition
For familial cancer patterns that suggest mutations in particular cancer-predisposing genes, specific DNA-based tests are available. The cost of genetic testing is separate from the cost of consultation. Testing is often performed at outside reference laboratories.
Ideally, genetic testing is first performed on a blood sample from an affected, living person with a high pretest probability of carrying a germline mutation. In some, tumor blocks from deceased, affected relatives may be used. The Cancer Genetics team identifies key family members for genetic testing, facilitates communication among relatives with strict attention to confidentiality, and obtains blood or tumor blocks by using appropriate consent procedures. For key relatives who do not live in the Pittsburgh area, the cancer genetics team coordinates genetic counseling and testing via an international network of genetic counselors and medical geneticists.
In general, it is necessary to screen the entire DNA sequence of the putative cancer-predisposing gene(s) in the first person tested in the family. This initial phase of testing is therefore the most expensive (about $1,000 to $3,000). If a specific cancer-predisposing mutation is identified in the affected family member, genetic testing can then be offered to unaffected relatives. Because genetic analysis is then targeted to the specific familial mutation, the cost decreases significantly for subsequent tests (to about $500 to $800).
When a family's ethnic background and pattern of cancers permit analysis of a narrower array of mutations, the cost of testing may be performed in a stepwise fashion. This targeted analysis may identify a mutation at a lower cost (about $750), but full genetic analysis may be required if no mutation is thus identified. Stepwise approaches are also helpful for stratifying colon cancer genetic testing by analyzing tumor tissue for genetic instability, a genetic footprint for some inherited mutations.
Most importantly, for those who test negative for the familial mutation, cancer risk can be assumed to approach that of the general population. Worry is diminished and aggressive surveillance and preventive methods become unnecessary.
Limitations of genetic testing
While the opportunity for DNA testing is an important part of the genetic counseling process, only about 10 percent of those with cancer are appropriate candidates for such tests. Others have family histories that do not suggest an inherited susceptibility to cancer, a pattern of inheritance that cannot be matched with a known cancer-associated gene, or a type of cancer for which no genetic tests exist. Prior to testing, individuals must understand the risks, benefits, and limitations of genetic testing for cancer predisposition.
Elements of informed consent for genetic testing
Informed consent exists when the patient understands the following:
- Purpose of the test.
- Clinical significance of either positive or negative results.
- Possibility that the test may not provide conclusive information.
- Options for risk assessment without genetic testing.
- Risk of passing mutations to children.
- Options for withdrawing from testing before completion or for postponing receipt of results.
- Medical options and limited proof of efficacy for screening and preventive measures.
- Technical accuracy of test.
- Risks for psychological distress.
- Possible risk of employment or insurance discrimination.
- Risk of discovering unexpected paternity.
- Notification procedures to be followed, including contingency plans in case of death of originally identified person.
- Specific means taken to protect confidentiality.
- Fees involved in counseling and testing, including insurance reimbursement for the test.
Above all, results of both genetic testing and risk assessment are kept at the highest level of confidentiality. Results are released to the individual, and it is the Cancer Genetics Program's policy to provide referring physicians with a summary letter and a copy of the results.
Addressing fears and concerns
An important part of the genetic counseling process is to address each person's emotional concerns. Throughout the genetic counseling process, support and counseling are given. Referral for additional psychological support may be recommended for some people.
Patients and their families may have theories as to the cause of the cancers. When these theories are inaccurate, the counseling team explains why; when these theories have some basis in truth, the team helps to optimize the person's understanding.
Because the questions raised in genetic counseling affect all family members, regardless of whether or not they have inherited a cancer-predisposition gene, relatives' reactions to the results of genetic counseling, and their potential desire not to know, are also addressed. Genetic counseling is, of course, also available to any family members who want it. Patients may also elect to have family members present for all or part of the counseling process. There is an additional cost for blood relatives who undergo genetic counseling and testing.
In most cases, patients overestimate their risk for developing cancer; genetic counseling can greatly reduce exaggerated fears. However, program specialists emphasize that a baseline risk of cancer exists for everyone.
Genetic consultation: An overview
Cancer risk consultation occurs over one to three visits, often depending on whether genetic testing is done. The Cancer Genetics Program offers unparalleled expertise in the region, bringing together the skills of genetic counselors, surgeons, and oncologists for the benefit of care. Board-certified genetic counselors as well as GI and endocrine surgery specialists join their premier capabilities in the genetic analysis of samples.
Typically, the purpose of genetic consultations is to:
- Determine a person's concerns and intentions.
- Review purpose of session.
- Record detailed family history of cancer and premalignant conditions and assess familial risk.
- Record medical history and suggest examination of the patient, if warranted, to rule out specific syndrome.
- Educate the person about genetics and cancer.
- Calculate cancer risk (e.g., for breast cancer), using epidemiological models and providing explanations.
- Discuss whether family history best fits a sporadic, familial, or hereditary (genetic) pattern.
- Discuss possible genetic syndromes that fit the familial cancer pattern.
- Identify key relatives to pursue release of their medical records by consent.
- Discuss feasibility of genetic testing, pretest probability for specific syndromes, risks and benefits of testing, and logistics of testing (cost, genetic discrimination, and confidentiality).
- Assess which malignancies the patient may be at risk for developing.
- Review screening and prevention steps for specific cancers.
- Address emotional issues.
- Identify relatives for possible participation in genetic counseling and testing and for whom the information may be of particular importance.
- Summarize, outline future steps, and leave open options for future contact, given evolving nature of cancer genetics field.
- Mail letter(s) summarizing consultation to referring physician and provide patients with written information regarding their risk assessment.
The first visit
Genetic counseling at the Cancer Genetics Program usually is initiated by a telephone call from the individual or referring physician. A clinic coordinator will obtain the basic history and determine the individual's primary concern. The coordinator will then schedule an appointment.
Prior to the appointment, a genetic counselor obtains a family history (usually of three or four generations), determines which medical records are important for documentation of reported cancers, and begins to work on a cancer pedigree (family tree).
The person's first visit follows. Ideally, the person will have his or her medical records sent before this visit. The counselor and the patient undertake a systematic review of family members with cancer, as well as those without cancer.
One of the central goals of genetic counseling is to develop surveillance and prevention strategies based on the person's risk of cancer. Prevention is discussed at the first meeting and can be revisited during any subsequent appointments. Lifestyle factors are covered, as are their limitations. The individual and clinicians also discuss screening methods, such as mammography or colonoscopy, and their potential benefits and limitations. Prophylactic surgery is discussed in depth, helping the patient to understand the potential benefits and risks involved. Chemoprevention options, such as tamoxifen and raloxifene for breast cancer, are explored. The opportunity for referral to surgeons, plastic surgeons, and other specialists is reviewed and coordinated with referring physicians at this time.
For those who meet generic testing criteria and wish to proceed, blood draw can be arranged at the time of the first visit after written informed consent has been obtained.
The second visit
While some people make the choice to undergo genetic testing at their first visit, blood draw is sometimes deferred until a second visit to allow the person to consider the situation more completely. At the second meeting, the medical record review is finalized, and lingering concerns and new questions generated by the first meeting are addressed. Written informed consent is then acquired.
Disclosure of test results
Genetic testing results are generally available two to four weeks after the blood sample is taken. At that point, the genetic counselor calls the individual to arrange a face-to-face disclosure meeting with the medical geneticist.
The counseling team will give the person another opportunity to refuse disclosure of the test results. Test results are generally given in person.
At the disclosure meeting, the medical geneticist and genetic counselor explain the test results. Any medical, emotional, or family issues that arise are also addressed. Preventive measures and screening tests are discussed further for the individual, based on test results. Family members for whom the genetic information may have a health impact are identified, and a plan for notification of relatives is devised in a manner that balances patient autonomy with responsibility to notify relatives who are at increased cancer risk. Those wishing to release test results to other family members are asked to sign a release form indicating specifically whom can receive results.
- Physicians can preview cases with Cancer Genetics Program specialists, or they can refer people directly to the program for preliminary information.
- A patient brochure is available on request. No charge is made until Cancer Genetics Program specialists actually see the person or family members.
- People may schedule genetic consultations at multiple sites in Pittsburgh, at Magee-Womens Hospital, or the Hillman Cancer Center. Up-to-date information on locations and days of operation can be obtained by calling the Cancer Genetics Program at 1-800-454-8156.
- To refer people for consultations, to obtain more information about cancer genetics or DNA testing, or for educational sessions for health care professionals, call 1-800-454-8156.