Genetic Counseling in Cancer: A Status Report

Genetic Counseling in Cancer: A Status Report

This special reference on genetic counseling in cancer is timely, given the explosive progress that has been made in cancer genetics in general and molecular genetics in particular during the past decade. For example, the discovery of "cancer-prone genes" and the identification of "new" hereditary cancer syndromes have had extensive coverage in both the scientific and lay press. As a result, patients around the world have been avidly seeking information from their physicians about how genes may be controlling their cancer destiny.

In turn, the slightest evidence of cancer in a patient's family may provoke crippling fright and anxiety. In some individuals, such responses may partially be due to their misinterpretation of the media accounts. Occasionally, however, the media presentations may be wholly or substantially inaccurate. The reports may have played down the importance of genetics in a particular cancer, giving patients a false sense of security or, alternatively, may have exaggerated genetic risk factors, thereby provoking unnecessary alarm and instigating expensive cancer screening.

The Physician's Responsibilities

A subset of these concerned patients may request some form of immediate remedial action, such as prophylactic removal of their breasts or ovaries, even though there may not be any solid genetic basis for their perception of increased cancer risk. In each case, it becomes the physician's responsibility to accurately interpret whether there is a reality base for patients' concerns about their genetic risk and to counsel them accordingly.

This requires that the physician accrue a sufficiently detailed family history with adequate documentation of cancer occurrences at all anatomic sites in order to formulate (or rule out) a hereditary cancer syndrome diagnosis. If such a diagnosis is established, the patient then needs to be informed about his or her personal risk for cancer and about available surveillance and management strategies, including their advantages and limitations.

When DNA testing is indicated, an explanation of the testing procedure must be conveyed to the patient. The possible penalties of genetic disclosure must be discussed as well. For example, there is a risk that insurance companies may refuse coverage for cancer surveillance or even surgical prophylaxis (such as prophylactic oophorectomy in a BRCA1 carrier) because it is a "preexisting condition" or designate gene carriers as "uninsurable." Employers, especially those with self-insurance, may find it in their financial interests to discriminate against gene carriers.

As with any family, families with hereditary cancer are composed of individuals, with different emotional traits, experiences, and motivations that influence personal decisions. The results of gene testing for one individual may reveal the gene status of another who is adamantly opposed to that revelation. The emotional impact of identification as a gene carrier will vary from one individual to another, but patients need to be encouraged to anticipate their own reaction based on past experiences and existing support systems. Even noncarriers may feel guilty about their gene status (so-called survivor guilt). Clearly, all of these matters are integral features of the genetic counseling process.

Information Supply Lags Behind Demands

Are physicians sufficiently knowledgeable and ready to perform genetic counseling? Are they adequately trained to supervise cancer genetic counselors? Are guidelines for cancer genetic counseling available? Are there enough available certified genetic counselors who are sufficiently knowledgeable about cancer genetics and the natural history of these disorders? This knowledge is essential so that patients can receive, and intelligently act upon, recommendations based on accurate genetic risk information, so that, in turn, appropriate choices about surveillance and management strategies (inclusive of their limitations) can be entertained.

A gap exists between what is known about cancer genetics and patients' counseling needs and their demands for information and realistic cancer prevention measures. Such a state of affairs should not be surprising, however, given the embryonic status of the newly emerging disciplines of cancer genetics and molecular genetics. For example, we are still low on the learning curve relative to our understanding of the variation in penetrance and expression of cancer-prone genes, particularly with respect to age of onset, tumor spectrum, pathology, and prognosis. Questions about each of these issues abound.

We also have insufficient information about the multifaceted legal, ethical, and moral issues that may impact on genetic counseling. For example, what is the potential for malpractice litigation that may emanate from the genetic counseling process?

Appropriate Action Needed

The list of potential concerns about genetic counseling in hereditary cancer could be extended almost interminably. While full and complete answers to these questions may require many years of research (and some may be so elusive as to never be fully clarified), we, nevertheless, must appreciate the fact that if the medical community does not take appropriate action about cancer genetic diagnosis, genetic counseling, and management, patients will seek advice from individuals with less training. Given market demands, untrained health-care professionals may be pressured into providing services with implications that they neither understand nor appreciate.

In order to meet these many needs of patients and their physicians in relation to hereditary cancer, we have opened a Hereditary Cancer Prevention Clinic in Omaha, Nebraska (fax, 402-280-1734). This clinic will provide various services for patients with all varieties of cancer, including cancer genetic diagnosis, genetic counseling, surveillance, and management.

Should DNA Testing Be Put on Hold?

A constant theme in this symposium centers around the explosive advances in molecular biology and genetics and how these discoveries have outpaced the physician's ability to translate this knowledge into patient management. In this regard, highly skilled genetic counseling is mandatory before patients undergo DNA testing and, of course, during and after disclosure of the results. Intensive continuing medical educational programs in the medical school curriculum and postgraduate programs could close the information gap. These programs would enable physicians to become more knowledgeable about the diagnostic capabilities of DNA testing. They would also learn about its limitations, including discrimination that might be inflicted on patients by insurers and employers, as well as the psychological sequelae that may befall patients and their families.

These concerns have led to the suggestion by some that we put a halt to DNA testing for genetic disorders until the intellectual void in this transitional period is closed! Several documents issued in the United Kingdom [1], the United States [2], and the Netherlands [3] have pointed to the need for caution when translating molecular genetic knowledge into clinical practice. These admonitions have included breast cancer genetic susceptibility testing [4], as well as the genetic testing of children [5,6].

In reviewing this subject, Harper [7] notes that several European countries, as well as the European Union, have considered the introduction of laws to regulate genetic tests, whereas Norway has already enacted such legislation [8].

Power to Save Lives

Of course, caution is advisable in any new discipline. However, it would seem foolhardy to wait for new insights to emerge when we have at hand the power to save lives through the utilization of DNA knowledge. This concern is best demonstrated in the paper on MEN-2 by Grosfeld et al. Prior to RET testing, the identification of patients at risk for MEN-2 required biochemical testing (pentagastrin stimulation of calcitonin). However, false-negative and false-positive results were known to occur and, in certain cases, were disastrous.

These problems have been largely circumvented by the use of the RET test; at present, once an MEN-2 family is recognized, children at risk can be tested, thereby enabling primary prevention (total thyroidectomy in the RET- positive individuals) before the development of even small foci of medullary carcinoma. The point is, had we put a halt to DNA testing and its clinical application, the medical benefit to countless MEN-2 patients who are candidates for prophylactic surgical thyroidectomy would have been curtailed, with resultant morbidity and mortality.

How many patients with other hereditary cancer-prone disorders may benefit from the primary prevention afforded by DNA knowledge? Should we put these matters on hold, until, for example, more knowledge is accrued about the adenomatous polyposis coli (APC) germ-line mutation in familial adenomatous polyposis (FAP), or about the mutated genes in hereditary nonpolyposis colon cancer (HNPCC); namely, MSH2, MLH1, PMS1, and PMS2? For such disorders, DNA evidence is the only way of determining profound cancer susceptibility, given the absence of premonitory stigmata (the Muir-Torre variant of Lynch syndrome II excepted).

A Complex Issue

The issue, as we perceive it, is a very complex one. However, we have elected to use the molecular genetic knowledge gleaned through the discovery of the genes responsible for the hereditary breast-ovarian cancer (HBOC) syndrome and the Lynch syndrome II in genetic counseling [9,10]. We have done so primarily because of our conviction that knowledge of individuals' germ-line mutation status for cancer can reduce morbidity and mortality through early detection or prophylactic surgery.

Clearly, we have restricted this DNA-based genetic testing to families for which we are highly confident that a hereditary cancer-prone syndrome exists and for which family members have provided informed consent prior to DNA testing and disclosure of results of such testing. When our research studies were initiated many years ago in some of the HBOC and Lynch syndrome kindreds in our resource, we advised these high-risk patients that one day scientific progress would likely enable many of the discoveries that have since taken place and that are now common knowledge to the medical profession, as well as to the laity.

More Research Clearly Mandatory

Given this perspective, it is clearly mandatory that more research be performed with respect to all facets of DNA testing and genetic counseling, as well as surveillance and management approaches based on the powerful translational potential of knowledge of DNA findings. Furthermore, we believe that it would be preferable for this research to be performed at centers where physicians are highly experienced in oncology and genetics and have worked extensively with cancer-prone families. Ideally, such groups should have consultants who are skilled genetic counselors, social workers, and psychologists who are knowledgeable about how this DNA information may impact upon insurability, employability, intrafamily strife, and emotions, as discussed in both special issues of this journal.

It would seem to be at cross-purposes to withhold this information from patients when benefit could be accrued. Thus, given this background, we believe, with all due respect to caution, that clinicians have a compelling and, indeed, an ethical responsibility to provide DNA test results to informed and consenting family members.

The Psychological Impact of Testing

Lerman and Croyle have been pioneers in elucidating the psychological impact of DNA testing. They have studied the manner in which underlying societal and psychological stress may influence health education, risk perception, and compliance, and thereby, how this stress may modify health behavioral changes among individuals at high risk for cancer who might benefit from genetic testing services. These authors modestly suggest that their work has highlighted only a small subset of issues and research findings from the behavioral sciences that are relevant to clinical practice. They appropriately conclude that "only by overcoming the boundaries of discipline, department, degree, and tradition will the new genetics eventuate in a better quality of life for patients, their families, and the clinicians who serve them." This concern is most fitting and challenging, and should be an impetus to move ahead with continued caution and an abundance of compassion for patients who continue to help us learn how to use DNA findings in the interest of cancer control.

Role of the Genetic Counselor

Peters and Stopfer clarify how the genetic counselor fits into the overall scheme of DNA translation in the albeit often ambiguous relationship between the physician and the patient, a problem that is best defined by them in terms of the need for "...a communication process between health care professionals and an individual concerning the occurrence, or risk of occurrence of cancer in his or her family [which] comprehensive in scope, and includes a strong emphasis on the familial nature of cancer and an analysis of genetic and related risk factors."

Cancer Genetics and the Law

How does the legal profession view cancer genetics, the implications of DNA testing, and the needs of the cancer-susceptible individual to benefit from those scientific advances, where particular attention must be given to the responsibilities of the physician and genetic counselor? Dr. Severin, an epidemiologist and a lawyer, reviews this subject by depicting several early civil suits filed by the lawyers of dissatisfied patients or their families. In these cases, charges were made against physicians because of their presumed negligence and liability during the management of the particular patient.

The usual legal issues have been litigated in these settings, including harm to patients by failure to diagnose a hereditary cancer syndrome, in particular, where this failure resulted in a significant alteration of the prognosis and/or the timeliness of targeted therapy. Case reports highlight instances where there was a physician's "...failure to suggest monitoring or screening procedures for the siblings, children, or even parents of the patient with an identifiable hereditary cancer, [and] failure to keep adequate records of cancer incidence in a family when the physician assumed the care of the family with a heritable cancer history."

If readers become frustrated because of the often complex problems in the genetic counseling of patients at risk for hereditary cancer addressed by the contributors to these special issues, we will consider our mission to have been accomplished. Historically, scientific advances in medicine have been furthered by strife and conflict. DNA-based genetic counseling is no exception to this axiom!

Many of the concerns discussed in this overview are addressed by my colleagues in this special ONCOLOGY reference. The authors fully appreciate the fact that, in many cases, before the ink has dried, newly emerging data will have made their remarks obsolete. I wish to express my gratitude to these contributors who unselfishly took time from their very busy research and clinical activities to prepare manuscripts for this reference.


1. Nuffield Council on Bioethics: Genetic Screening: Ethical Issues. London, Nuffield Foundation, 1993.

2. Andrews LB, Fullerton JE, Holtzman NA, et al: Assessing Genetic Risks: Implications for Health and Social Policy. Washington DC, National Academy Press, 1994.

3. Genetic Screening. Report of a Committee of the Health Council of the Netherlands. The Hague, Health Council of the Netherlands, 1994.

4. Statement of the American Society of Human Genetics on genetic testing for breast and ovarian cancer predisposition. Am J Hum Genet 55:1-4, 1994.

5. Working Party of the Clinical Genetics Society: The genetic testing of children. J Med Genet 31:785-797, 1994.

6. American Society for Human Genetics/American College of Medical Genetics report: Points to consider: Ethical, legal and implications of genetic testing in children and adolescents. Am J Hum Genet 57:1233-1241, 1995.

7. Harper PS: Genetic testing, common diseases, and health service provision. Lancet 346:1645-1646, 1995.

8. Biotechnology Related to Human Beings. Oslo, Ministry of Health and Social Affairs, 1993.

9. Lynch HT, Watson P, Conway TA, et al: DNA screening for breast /ovarian cancer susceptibility based on linked markers. Arch Intern Med 153:1979-1987, 1993.

10. Lynch HT, Drouhard T, Vasen HFA, et al: Genetic counseling in a Navajo hereditary nonpolyposis colorectal cancer kindred. Cancer 77:30-35, 1996.

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