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
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 , the United States , and the
Netherlands  have pointed to the need for caution when translating
molecular genetic knowledge into clinical practice. These admonitions
have included breast cancer genetic susceptibility testing ,
as well as the genetic testing of children [5,6].
In reviewing this subject, Harper  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 .
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
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
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]...is 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
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
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
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,
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
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.