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 patient elects to forego testing, using epidemiological models and computer algorithms. Cancer risk specialists, the patient 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 -- generally $150 to $280 for the first visit and less for subsequent visits if needed. Authorization for referral may be required. However, insurance companies vary greatly with regard to covering DNA testing. The risk of genetic discrimination seems minimal for claims covering genetic consultation; however, if genetic testing is pursued at later visits, the patient may choose the option of self-pay, since the content of such discussions is otherwise open to review by the insurer.
For familial cancer patterns that suggest mutations in particular cancer-predisposing genes, specific DNA-based tests are available. (See table.) 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 $750 to $2,400). 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 $300 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 $200 to $500), 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.
In addition, some families are suitable for linkage analysis, which requires the participation of multiple family members. Linkage analysis is useful when the involved gene is mapped but not yet cloned, or a mutation cannot be identified with current technology in a known gene.
Most important, 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.
While the opportunity for DNA testing is an important part of the genetic counseling process, only about 10 percent of oncology patients 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, patients must understand the risks, benefits and limitations of genetic testing for cancer predisposition.
To ensure adequacy of informed consent for genetic testing, the Cancer Genetics Program follows a protocol approved by the University of Pittsburgh Institutional Review Board (IRB). This IRB affords the opportunity to follow patients prospectively, allowing the program to address questions about the penetrance (i.e., probability that a genetic mutation will be expressed clinically) of cancer, efficacy of surveillance and prevention and other crucial questions.
Informed consent exists when the patient understands the:
Above all, results of both genetic testing and risk assessment are kept at the highest level of confidentiality. Results are released to no one other than the patient, unless he or she has signed an IRB-approved release indicating specifically to whom the results should go. Within these parameters, it is the Cancer Genetics Program's policy to provide referring physicians with a letter summarizing the genetic test results.
An important part of the genetic counseling process is to address each patient's emotional concerns. Throughout the genetic counseling process, support and counseling are given. Referral for additional psychological support may be recommended for some patients.
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 patient'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 receive counseling services.
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.
Cancer risk consultation occurs over one to three visits, often depending on whether genetic testing is explored. The Cancer Genetics Program offers unparalleled expertise in the region, bringing together the skills of medical geneticists who are board-certified in clinical genetics and clinical molecular genetics. Board-certified genetic counselors, GI and endocrine surgery specialists join together their premier capabilities in the genetic analysis of patient samples.
Typically, the purpose of genetic consultations is to:
Genetic counseling at the Cancer Genetics Program usually is initiated by a telephone call from a patient or referring physician. A clinic coordinator will obtain the basic history and determine the individual's primary concern. Then the coordinator will schedule an appointment. The fee for the initial consultation ($150 to $280 per person) is often covered by the patient's insurance company; additional visits will result in additional consultation fees. Primary care physicians may have to authorize consultations in order for insurance to cover fees.
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 patient's first visit follows. Ideally, the patient 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 patient's risk of cancer. Prevention is discussed at the first meeting and is revisited during any subsequent appointments. Lifestyle factors are covered, as are their limitations. The patient 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. Newer 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.
While some patients make the choice to undergo genetic testing at their first visit, phlebotomy is usually deferred until a second visit, to allow the patient 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 gained from the patient under a University of Pittsburgh IRB-approved protocol for genetic testing.
The counselor and medical geneticist make a final assessment of whether a genetic cancer predisposition is likely to exist, the most probable identity of the gene in question, whether a test exists for that gene and the cost of testing. Some insurance plans will reimburse for genetic testing, but many patients forgo making medical insurance claims for the test because they are concerned about insurance discrimination. Anonymous preview of insurance coverage for genetic tests is available in some cases. During the second visit, the patient decides whether to have a blood sample drawn for testing.
Evidence from the Breast Cancer Prevention Trial (BCPT), a study that helped to determine if tamoxifen is an effective method of breast cancer prevention, raises numerous questions about which women are likely to derive more benefit than harm from chemoprevention. Since treatment is appropriate only for women at increased risk, quantitative breast cancer risk calculations must be performed. Cancer Genetics Program staff perform these calculations using epidemiological and genetic risk models for all patients seeking breast cancer risk counseling.
For high-risk patients, the risks and benefits of chemoprevention using agents such as tamoxifen and raloxifene are explored in depth. Family history of osteoporosis, heart disease and venous thrombosis, as well as personal history of hysterectomy, birth control pill use, bone fractures, heart disease, menopausal status and hormone replacement therapy are assessed. A thorough discussion of the risks and benefits of chemoprevention is undertaken and a recommendation is made to the referring physician. Since chemoprevention is still based in the research arena, a strong recommendation is made to high-risk women who qualify to participate in ongoing chemoprevention trials and such participation is facilitated. The University of Pittsburgh Cancer Institute (UPCI) played a major role in the original BCPT trial and is participating in the STAR Trial, the largest study on breast cancer chemoprevention ever undertaken, along with a number of other trials.
Genetic testing results are generally available three to 12 weeks after the blood sample is taken. At that point, the genetic counselor calls the patient to arrange a face-to-face disclosure meeting with the medical geneticist.
The counseling team will give the patient another opportunity to refuse disclosure of the test results. No test results are given to patients over the telephone or by mail.
At the disclosure meeting, the patient signs an IRB-approved consent form allowing the team to disclose test results to the patient. 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 customized further for the individual patient, 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. Patients wishing to release test results to other family members and physicians are required to sign a release form indicating specifically who can receive results.
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