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© 2000 American Society for Clinical Oncology
Organizing Cancer Genetics Programs: The Swiss ModelFrom the Division of Oncology, Department of Medicine, University Hospital, Zürich, Switzerland. Address reprint requests to Gabriella Pichert, MD, Division of Oncology, Department of Medicine, University Hospital, Rämistrasse 100, 8091 Zürich, Switzerland; email onkpib{at}usz.unizh.ch
PURPOSE: Inherited predisposition to cancer is a complex issue, and risk assessment, counseling, and management are multidisciplinary tasks. An infrastructure is needed through which clinical services may be delivered and research activities conducted. METHODS: The Swiss Institute for Applied Cancer Research (SIAK) Network for Cancer Predisposition Testing and Counseling was established in 1999. The goals of the Network are to set common standards for clinical services, to coordinate research activities, to address psychosocial and ethical issues concerning genetic counseling and testing, and to translate the knowledge gained into medical practice. RESULTS: An algorithm for genetic testing and counseling of the families studied by the SIAK Network centers has been established in a consensual process. Eight regional centers currently operate according to this algorithm. Furthermore, a proposal has been submitted for the setup of a Swiss databank for the characterization of BRCA1 and BRCA2 mutation patterns and the identification of potentially unique mutations in probands who seek genetic counseling and testing at the respective centers of the SIAK Network. CONCLUSION: Our coordinated effort will ensure state-of-the-art genetic testing and counseling services in Switzerland and will allow us to acquire knowledge for appropriate risk assessment and surveillance/prevention strategies for individuals with an inherited cancer predisposition.
ADVANCES IN molecular biology have led to the discovery of mutations associated with inherited cancer susceptibility. This finding allows genetic testing and counseling of individuals and families at risk, with the goal to relieve uncertainties and anxieties and to enable them to make informed choices based on a comprehensive cancer risk assessment. However, much work remains to be done because our ability to make clinically proven interventions based on appropriate risk estimates and genetic testing is limited and the field of cancer prevention is in its infancy. Genetic testing and counseling of individuals with an inherited cancer susceptibility was the domain of medical geneticists until recently. With the identification of breast/ovarian1,2 and colon cancer susceptibility genes,3-8 oncologists, gynecologists, gastroenterologists, and many other health care professionals have become involved in the care of these individuals. No formal criteria have been established so far for physicians or allied health providers who choose to work in the new field of genetic cancer predisposition testing and counseling. Recently, the Swiss Society for Medical Genetics (SSMG) has defined a new subspecialty in medical genetics9 that consists of 3 years of training in medical genetics and 2 years of clinical training, with the aim to help guide clinicians to deliver state-of-the-art counseling and care to individuals with inherited predispositions and diseases. However, there may not be enough medical geneticists trained in this new field to satisfy the need of the cancer predisposition testing and counseling centers in Switzerland. The number of medical, social, ethical, psychological, and legal issues that have to be addressed to ensure appropriate cancer risk assessment and genetic counseling is daunting. This report focuses on questions that have been resolved by the Swiss Institute for Applied Cancer Research (SIAK) Network for Cancer Predisposition Testing and Counseling in 1999, as well as on the most pressing issues that need to be addressed during the year 2000.
The SIAK Network for Cancer Predisposition Testing and Counseling was established in 1999 with the support of the Swiss Cancer League.10 Among its members are medical and molecular geneticists, oncologists, gynecologists, gastroenterologists, surgeons, heads of cancer registries, pathologists, specialists in social and preventive medicine, psychiatrists, and nurses, the diversity of these members reflecting the multidisciplinarity of the field. The first goal of the SIAK Network was to establish an algorithm for genetic testing and counseling through a consensual process. Eight regional cancer predisposition testing and counseling centers work according to this algorithm at the time of this writing, namely Basle, Berne, Geneva, Lausanne, St Gallen, Sion, Ticino, and Zürich. Further goals of the Network are as follows: (1) to coordinate clinical and research activities, (2) to address psychosocial and ethical issues concerning genetic counseling and testing, and (3) to translate the knowledge gained into medical practice.
Coordination of Clinical Activities On the basis of excellent clinical guidelines published by many professional groups11,12 and taking into consideration the shortage of medical geneticists, an algorithm for genetic counseling of individuals observed by the SIAK Network for Cancer Predisposition Testing and Counseling has been defined. Figure 1 depicts the process for genetic counseling and testing of families who are studied by the regional cancer genetic centers. The counseling process is explained during the first visit (Fig 1, section 1A) to one or more interested family members by a medical geneticist and/or a clinician. Questions, concerns, and expectations of attending family members are addressed, and a three-generation family history obtained and consecutively confirmed with medical reports. When all the information has been collected, a multidisciplinary team convenes that consists of a medical geneticist, an oncologist, a nurse coordinator, and depending on the case, other specialists such as gynecologists, gastroenterologists, psychiatrists, pathologists, molecular geneticists, surgeons, general practitioners, or ethicists (Fig 1, section 2A). This team tries to answer five questions for the family studied: (1) Is it a known hereditary cancer syndrome? (2) Is a genetic test available, and should it be recommended? (3) What is the estimation of the individual risk to get cancer? (4) What measures of surveillance and prevention should be recommended? (5) Is psychological support needed?
At the pretest counseling session (Fig 1, section 3A), it is explained how genetics affect cancer susceptibility and an individual cancer risk assessment is given as well as an explanation of potential benefits, risks, and limitations of genetic testing to enable the subject to make a fully informed choice regarding whether potential benefits of genetic testing outweigh potential burdens. The individual at risk is provided with a written report of all important points discussed. If the subject decides to undergo genetic testing, written informed consent is obtained before blood is drawn. DNA testing is performed by laboratories in accordance with the guidelines of the SSMG and the Swiss Academy of Medical Sciences regarding genetic testing in humans and with the most recent draft of the federal law concerning genetic testing in humans. These laboratories follow the current quality control guidelines of the SSMG and take part in a quality control program recommended by the SSMG. For individuals not interested in genetic testing or when no genetic testing is available, appropriate surveillance measures are planned. At the posttest counseling session (Fig 1, section 4A), the original report of the test result is handed to the consultant and its significance explained. Depending on the test result (deleterious mutation, alteration of uncertain significance, or no detectable deleterious mutation), the appropriate surveillance and prevention recommendations are given. Psychological care is offered. Every effort is made to invite individuals at risk to participate in clinical surveillance and prevention studies. For example, individuals with a mutation associated with hereditary nonpolyposis colon cancer or patients with colon cancer with a family history that meets the Amsterdam criteria will be offered participation in the Concerted Action Polyposis Prevention study, a European Union Biomed 1 program, in which the effect of aspirin and/or resistant starch on the prevention of appearance or progression of polyps in patients with hereditary nonpolyposis colon cancer is examined. This study is supported by SIAK. The European Familial Breast Cancer Collaborative Group, a group of clinicians who specialize in familial breast cancer, was established in 1996. A survey of current policies for surveillance and management in women at risk for breast and ovarian cancer performed among 16 participating cancer risk clinics13 demonstrated that most recommendations were based on expert opinion and varied at different centers. Therefore, the next issue to be addressed within our Network is how to perform risk assessment and to establish evidence-based guidelines for surveillance and cancer prevention for individuals with an inherited breast/ovarian and colon cancer susceptibility.
Coordination of Research Activities
Psychosocial and Ethical Issues Concerning Genetic Testing and Counseling The attitudes, knowledge, and perception of the general public and primary physicians toward genetic testing and counseling and preventive measures are largely unknown in Switzerland. Therefore, the SIAK Network will conduct a survey to obtain data on issues from the following: (A) Individuals at risk who seek genetic testing and counseling:
(B) For primary care physicians:
The complex medical, social, ethical, and legal aspects surrounding genetic testing need a comprehensive approach because the field of cancer genetics is dynamic, fast accumulating knowledge from research and rapidly evolving laboratory techniques. We thought that a network of cancer predisposition testing and counseling centers was best suited to provide an infrastructure with common standards, through which interdisciplinary studies of medical and psychosocial issues could be conducted and state-of-the-art patient care provided. The algorithm for genetic counseling and testing of individuals with a hereditary cancer predisposition studied by the regional centers of the Network will guarantee comprehensive genetic counseling and cancer risk assessment. Moreover, it will ensure that genetic testing remains only one of the tools used in the process of assessing familial cancer risk and that confusion and inappropriate use of testing are avoided. Cancer predisposition gene penetrance is highly variable and influenced by many factors, such as the type of mutation and modifying genetic and environmental factors. For the two breast cancer genes BRCA1 and BRCA2, penetrance estimates vary depending on the population being examined.17,18 For example, the cumulative risk of breast cancer for women with inherited breast cancer, such as BRCA1 or BRCA2 carriers, is as high as 37% to 87% by the age of 85 years in some families.19,20 The risk of ovarian cancer has also been calculated to be anywhere from 15% to 60% by the age of 85 years in some BRCA1 carriers. The setup of a Swiss databank for BRCA1 and BRCA2 mutations will make interpretation of test results faster, simpler, and more reliable, and a centralized databank will allow an international collaboration to correlate BRCA1 and BRCA2 mutation pattern results with known breast/ovarian cancer risk factors and other parameters that modulate the penetrance of these mutated genes. Attitudes toward genetic testing and interest in cancer risk reduction measures are influenced by medical as well as many other factors, such as race,21 ethnicity, cultural identity,22,23 risk perception, and strength of family history. Several United States–based studies underline the importance of psychological rather than medical factors in influencing individual decisions about genetic testing.21,22 It is generally agreed that the increasing demand for cancer genetic services will make the active participation of primary care physicians essential. However, several surveys have demonstrated that general practitioners may lack the knowledge24 or time to play an active role.25 The findings of our survey will provide data regarding knowledge, attitudes, behavior, and practices of the public and primary care physicians in Switzerland as well as the perception of the subjects toward how the members of the SIAK Network provide this service. These data are needed to successfully introduce the emerging field of cancer risk assessment and prevention to the public and to integrate genetic testing and counseling into clinical practice.
Representatives of the regional counseling centers are as follows: Basle—H.J. Müller, MD, Abteilung Medizinische Genetik, Universitäts-Kinderklinik; H. Müller, PhD, Universitäts-Frauenklinik Biochemische Endokrinologie; and W. Weber, MD, Beratungsstelle Für Familiäre Tumorerkrankungen, Abteilung Für Onkologie am Kantonsspital. Berne—S. Braga, MD, and K. Buser, MD, Genetische Beratung Engeriedspital, and M. Castiglione, MD, and R.A. Stahel, MD, SIAK Koordinationszentrum. Geneva—S. Antonarakis, MD, and C. Delozier-Blanchet, MD, Centre Médical Universitaire, Division Génétique Médicale, and A.P. Sappino, MD, and Anne Murphy, RN, Unité d‘identification des prédispositions génétiques aux cancers, Division d‘Oncologie, Hôpital Cantonal Universitaire. Lausanne—L. Perey, MD, Centre Pluridsciplinaire d‘Oncologie, Centre Hospitalier Universitaire Vaudois , and D. Schorderet, MD, Division autonome de Génétique Médicale. St Gallen—B. Bolliger, MD, A. Glaus, PhD, and H.J. Senn, MD, Onkogenetische Beratung, Zentrum für Tumordiagnostik und Prävention. Sion—P. Hutter, PhD, and V. Membrez-Antonioli, MD, Consultation Genetique, Institut Central des Hôpitaux. Ticino—S. Braga, MD, O. Pagani, MD, and P. Saletti, MD, Centro Di Consulenza Genetica Oncologica, Ospedale Beata Vergine, and Ospedale San Giovanni. Zürich—G. Pichert, MD, Beratungsstelle für Personen mit genetisch bedingtem Krebsrisiko Universitätsspital, and M. Schinzel, MD, Institut für Medizinische Genetik.
Supported by the Swiss Institute for Applied Cancer Research and the Cancer League of Zürich, Zürich, Switzerland.
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Copyright © 2000 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
