Ethics of predictive DNA-testing for hereditary breast and ovarian cancer

Patient Education and Counseling 35 (1998) 43–52

Ethics of predictive DNA-testing for hereditary breast and ovariancancer

*Guido de Wert

Institute for Bioethics, University of Maastricht, P.O. Box 616, 6200 MD Maastricht, The NetherlandsErasmus University, Rotterdam, The Netherlands

Received 20 October 1997; received in revised form 13 May 1998; accepted 19 May 1998

Abstract

The recent identification of gene mutations involved in hereditary cancers increasingly allows for predictive DNA-testing.There is an urgent need to analyse the ethical issues involved. This article concentrates on the ethics of predictive testing formutations in the breast (and ovarian) cancer genes BRCA1 and -2. Using international guidelines for presymptomaticDNA-testing for Huntington disease and the Li-Fraumeni syndrome as a model, a provisional protocol, which entails fourparts is presented: (i) inclusion and exclusion criteria; (ii) preparing for the test; (iii) informing about the results of the test;(iv) post-test counselling and evaluation. The importance of an integral education of both doctors and the public is stressed. 1998 Elsevier Science Ireland Ltd. All rights reserved.

Keywords: Ethics; Predictive genetic testing; Hereditary breast cancer; Protocol

1. Introduction urgent need to analyze the ethical issues involved.How can predictive testing for hereditary cancers

While most cancers result from acquired genetic best be incorporated into health care? What is goodalterations in somatic cells, some cancer patients clinical practice?have inherited mutations that play a central role in This article focuses on predictive testing forthe aetiology of their disease. In the past few years, mutations in the BRCA1/-2 genes, which haveseveral major genes involved in various types of received a lot of attention in the scientific andcancer have been identified. These discoveries allow popular media. Relevant medical and genetic datafor predictive DNA-testing, aimed at identifying can be found in the previous issue of this journal [1].individuals at (very) high risk. There is no doubt that Occasionally, I will refer to the Li-Fraumenithe Human Genome project will lead to the identifi- syndrome (LFS). LFS is a rare syndrome, in whichcation of many more relevant mutations. There is an mutations of a gene called p53 are transmitted by

autosomal dominant inheritance and may cause*Tel.: 1 31 43 3882145; fax: 1 31 43 3671058. tumours in multiple organs, including early breast

0738-3991/98/$19.00 1998 Elsevier Science Ireland Ltd. All rights reserved.PI I : S0738-3991( 98 )00082-2

44 G. de Wert / Patient Education and Counseling 35 (1998) 43 –52

cancer and childhood sarcoma [2]. Most cancers have been used as a model [5–7]. The protocol hasassociated with LFS are very difficult to treat. In four parts:view of the wide age of onset, and the fact thatcancers can occur anywhere in the body, devising an 1. Inclusion and exclusion criteriaeffective screening programme, aimed at timely 2. Preparing for the testdetection, presents a very difficult, if not impossible 3. Informing about the results of the testtask. 4. Post-test counselling and evaluation

2. Ethical analysis4. Inclusion and exclusion criteria

A preliminary moral question is whether it isethically justified to presymptomatically test for late 4.1. Postnatal testingonset disorders when effective preventive and/ortherapeutic measures are not available (Huntington BRCA mutation identified in affected rela-disease, HD) or highly speculative (LFS). There is tive(s). At present, there is broad agreement that ifno uniform answer to this question. The World genetic testing is to be done, the first person tested inMedical Association recommends ‘that this type of the family should be a patient. This approach maxi-diagnosis for a predicted condition be performed mizes the information obtained from testing [8]. Ifonly when a therapeutic or prophylactic remedy is this patient carries a pathogenic mutation, any bloodavailable or when an estimate of the risk of transmis- relative can then be presymptomatically tested forsion can assist parents in making reproductive deci- that specific mutation. This inclusion criterion shouldsions’ [3]. Many hold that this position is too be handled with some flexibility, for instance whenrestrictive. First, this recommendation neglects that affected relatives have all deceased.individuals at risk may have good reasons to apply While the ethics of testing for hereditary late onsetfor the test even if they do not plan to have a family disorders regularly focuses on presymptomatic test-and if therapeutic or prophylactic remedies are not ing, the preceding diagnostic genetic testing ofavailable. Furthermore, the recommendation neglects patients raises some questions too. First: when isthat for some persons at risk the uncertainty about offering such testing indicated? Many centres offertheir genetic status is unbearable. Third, experience testing to affected women with at least a 10–15%with presymptomatic testing for HD until now likelihood of carrying a BRCA mutation. (Thesuggests that most clients can integrate the test result likelihood of a patient carrying BRCA mutations canin their life [4]. Obviously, this finding should be be estimated on the basis of some of the characteris-interpreted with caution. Indeed, this finding only tics of the disease and its pattern of inheritance in theapplies to testees who received intensive pre- and family-vertical transmission, number and type ofposttest counselling. Furthermore, the long term tumours, age of onset.) Of course, any specificeffects should be studied. demarcation point (5%, 10%, 20%, . . . ) is somewhat

arbitrary. One should realize, however, that what isat stake is, amongst others, the issue of the just

3. A protocol allocation of scarce resources. After all, broadeningthe indications for testing patients would substantial-

In view of the potential psychosocial risks of ly increase financial costs and would create logisticalpresymptomatic testing, it is important to establish a problems in view of the high workload, while itprotocol, to set a standard of good clinical practice. would identify relatively few carriers (and relativesBelow, a provisional protocol will be sketched. The at risk). An additional argument for a somewhatinternational guidelines for presymptomatic DNA- conservative policy may be that the penetrance ofdiagnosis of HD as well as the American and Dutch BRCA-mutations present in less-affected familiesguidelines concerning predictive testing for LFS (i.e. families with few affected patients) is currently

G. de Wert / Patient Education and Counseling 35 (1998) 43 –52 45

unknown, thereby complicating the counselling pro- test) is especially problematic when preventive orcess. therapeutic measures which have proven efficacy are

A second question is: which test(s) should be used not yet available.in diagnostic testing? Sequencing the entire BRCA1/-2 genes is, of course, most informative, but very Competence. An adequate understanding of thetime-consuming and expensive. For this reason, most implications of presymptomatic DNA-testing is acentres opt for more limited testing (using, amongst prerequisite for such testing.others, the so-called protein truncation test, which If preventive / therapeutic remedies are not (yet)can identify approximately 60% of the BRCA muta- available or highly speculative, the question arisestions). A disadvantage of this strategy is, of course, whether the doctor may refuse to give access tothat a substantial number of carriers among the predictive testing for paternalistic reasons, i.e. on thetestees will not be identified. Obviously, a difficult basis of the ‘best interests’ of the client, and if yes,balancing of needs and responsibilities is requested. on what conditions. Relevant in the ethical discus-It is hoped that new technology will substantially sion is the distinction between weak and strongreduce time and costs involved in BRCA-testing. paternalism [10]. Strong paternalism is the view that

A third aspect concerns the importance of it can be right to interfere with a person’s substan-adequate counselling of the patient and her relatives. tially autonomous decision for his own good. WeakIn many cases, testing the patient for BRCA muta- paternalism holds that it can be right to interfere withtions will not be informative. Counselling should a person’s less-than-substantially autonomous deci-help individuals to cope with the continuing uncer- sion making for his own good. Weak paternalism istainty regarding the potentially hereditary nature of not really controversial, because it involves no majorthe cancer in the proband, and regarding their genetic violation of the principle of respect for autonomy;status. At the same time, counselling can prevent those whose wishes and preferences are overriddenfalse reassurance – after all, a ‘negative’ test result are acting with less than substantial autonomy. Thein a given family does not exclude the hereditary issue of real controversy is strong paternalism. Somenature of the cancer in this family. consider such paternalism (regarding substantially

In view of the presumed future availability of autonomous persons) to be justifiable too, on themore informative tests, the counsellor should also condition that (a) there is substantial evidence thatdiscuss the option of recontacting the patient (the otherwise the client will be in grave danger, (b) the‘genetic recall’). overriding of the client’s wish offers a reasonable

prospect of bringing about a net benefit to him, (c)Voluntariness. The experience with presymptomatic such overriding is the least restrictive way to achievetesting for HD shows that external (‘third party’) the desired protection (of his best interests). Criticspressure is a serious problem [9]. Such pressure may of strong paternalism consider this guideline /policytake various forms. First, pressure from family to be unjustified, because it insufficiently respects themembers, more in particular the partner or children. client’s well-considered, subjective weighing of ben-Second, pressure from professionals. In view of this efits and harms, risks and chances, of submitting toexperience, it must be anticipated that third party the test.pressure can also arise in the context of DNA-testing Notwithstanding the latter controversy, it seemsfor cancer susceptibility. Substantial control by third justified (a) to offer (mandatory) pre-test counsellingparties would make the consent given invalid. The (‘psychological screening’) as a condition for accessprinciple of respect for autonomy implies that the to presymptomatic testing, given the importance ofcounsellor has the responsibility to check whether checking the applicant’s capacity for autonomousthe request for the test can be considered to be decisionmaking; (b) to postpone testing in case ofsubstantially voluntary. A second implication con- significant doubt concerning an applicant’s compe-cerns the importance of the principle of non-direc- tence.tivity of professionals. A directive attitude (recom-mending a person at risk to have the presymptomatic Only adults – as a rule. A major issue is whether


(healthy) minors can justifiably be tested for muta- minors who ask for the test themselves), the interna-tions for late(r) onset disorders, and, if yes, on what tional guidelines for HD-testing recommend that ‘theconditions. At least two questions need to be consid- test is only available to individuals having reachedered. First: is it appropriate to presymptomatically the age of majority’. Many commentators argue thattest incompetent children at the request of their this recommendation be followed in protocols con-parents? And second: is it appropriate to test minors cerning predictive testing for BRCA1/-2 mutationswho ask for such testing themselves? [14,15]. An alternative guideline is that the capacity

In some situations, predictive testing for childhood to understand is the appropriate criterion – whatdisorders allows for effective preventive interven- matters is not age as such, but the (in)competence oftion. Good examples are predictive testing for multi- the individual minor applicant. ‘Emancipatedple endocrine neoplasia 2a (MEN2A) and for retino- minors’ should not a priori be denied access to theblastoma. In these cases, testing is clearly appro- test.priate. A question needing further analysis, iswhether parental refusal to give proxy consent for 4.2. Controversial exclusion criteriapredictive testing could ever constitute medicalneglect, warranting societal intervention. Subjects at 25% risk and monozygotic twins at

A different picture emerges with regard to untreat- 50% risk. Difficult conflicts can arise when testingable late onset disorders, like HD. There is a strong the applicant will – or can – provide diagnosticconsensus that predictive testing of minors (at the information about another person at risk who has notrequest of the parents) would be inappropriate, for at requested the test. Situations like these mostly in-least two reasons [11]. First, the children’s right not volve applicants at 25% prior risk, whose parent atto know, i.e., their right to decide for themselves at risk (50%) does not want to know his genetic status.some stage whether or not to be presymptomatically A similar situation concerns a twin of a monozygotictested, should be respected. (This right belongs, I twin pair at risk (50%) who applies for pre-think, to the class of anticipatory autonomy rights, symptomatic testing while the other twin does notprotecting the child’s right to an ‘open future’ [12].) want to know. Testing the applicant (i.e. respectingSecond, such testing could cause serious harms, his right to know) could conflict with the relativesincluding damage to the child’s self-esteem and right not to know. Which (or whose) right shoulddistortion of the family’s perception of the child. prevail?

Apparently, some parents insist that their minor Ethical commentaries at this dilemma have, untilchildren be presymptomatically tested for mutations now, focused mainly on HD [16]. On the one hand,in BRCA1/-2 [13]. Again, such testing seems un- it is argued that giving priority to the relative’s rightwarranted, at least at first sight. After all, while the not to know is at odds with the principle of respectpsychosocial risks of such testing to children are for the autonomy of the applicant. Furthermore,substantial, preventive medical interventions can would it not constitute an intolerable breach of theonly be initiated when the child has reached adult- principle of equal access to health care if personshood. Clinical experience, however, shows that some presenting themselves for the test are selected ac-parents can not cope with uncertainty concerning the cording to whether or not their relatives claim thegenetic status of their children at risk. Such uncer- right not to know? On the other hand, proponents oftainty, and subsequent behaviour in parents, may a restrictive policy argue that the principle of non-have detrimental effects on the development of maleficence should take priority. Testing the applic-children. In view of this clinical experience, the ant may cause the relative immense stress, and hasquestion as to whether testing minors (at the request even resulted in suicide [17].of the parents) for adult onset, (potentially) treatable In view of the complexity of these cases, adisorders, like familial adenomatous polyposis and univocal guideline may not be appropriate. Handlinghereditary breast cancer, might be justified in in- the current type of conflicts is especially difficultdividual cases, needs further ethical debate. when the request concerns a late onset disease for

With regard to the second issue (the testing of which preventive or therapeutic measures are not


(yet) available, like HD. The availability of preven- disagree with this criticism, and point to the grimtive measures, however, has moral relevance, in that preview of the future. Prenatal testing for BRCAthe relative moral weight of the applicant’s right to mutations might be even more controversial, becauseknow will increase. As effective preventive methods the penetrance of these mutations is incomplete, andemerge, e.g. for carriers of BRCA1/-2 mutations, preventive interventions may effectively reduce mor-overruling the applicant’s right to know in view of a bidity and mortality in carriers. According to Collins,relative’s right not to know will be increasingly a leading American geneticist, ‘A host of moral anddifficult to justify. ethical issues make it inappropriate to offer testing

for breast and ovarian cancer susceptibility as part ofApplicants who do not want to participate in prenatal diagnosis’ [14]. One might, however, argue(post-test) evaluation studies. Predictive testing for that parents should be allowed to opt for thisbreast cancer genes should be undertaken only in the intervention [21]. After all, the effectiveness of thecontext of research protocols (cfr Section 7). Wide- various preventive interventions for women carryingspread clinical application of such testing without a BRCA mutation still has to be proven. Further-proper previous evaluation is unwarranted. However, more, parents may be worried about the prospect thatpredictive testing is sometimes considered, by both their carrier-daughter may have to opt for aprofessionals and potential users, as a clinical service prophylactic bilateral mastectomy (and oophorec-and not as a research activity [18]. This may result in tomy).a lack of follow up data, hampering a thorough If a woman intends to complete the pregnancyevaluation. In view of the relevance of such data, irrespective of the result of prenatal testing, there isapplicants should be encouraged to participate in no valid reason for prenatal testing for breast cancerfollow up research, and to adhere to the provisions of genes. A similar exclusion criterion has been rec-the research protocol. There is no consensus on the ommended for prenatal HD-testing [5]. The mainquestion whether such participation is a legitimate argument is that prenatal testing would be equivalentcondition for access to predictive testing. On the one to predictive testing for late onset disorders inhand, participation in evaluation studies is consid- childhood, which is unwarranted [16,22].ered to be a legitimate expectation of those offering A new technique is pre-implantation geneticthe testing programme, in view of its experimental diagnosis (PGD), aiming at a selective transfer ofcharacter. Critics, on the other hand, hold that it is unaffected (non-carrier) IVF-embryos, and avoidingnot justified to require applicants to participate in a the potentially traumatic experience of a selectiveresearch protocol if they do not want to (e.g. because abortion. It is expected that PGD will increasinglythey feel it is emotionally burdensome). become an option for the prevention of late onset

disorders, like HD, and hereditary forms of cancer4.3. Prenatal testing [23]. There is an ongoing debate about the ethics of

PGD [24]. In some countries, PGD is currentlyThe demand for prenatal testing for late onset forbidden. In other countries, PGD is legally al-

disorders like HD has been (very) low up until now lowed, though sometimes only for a limited number[19]. The demand for prenatal testing for breast of indications. It may be argued that if regularcancer genes may be even lower in view of the prenatal diagnosis of late onset disorders is allowed,incomplete penetrance of the various mutations and PGD for these disorders cannot consistently bethe presumed potential for prevention. rejected.

The current ethical debate concentrates on prenatal It has recently been suggested to offer carriertesting for HD. Some critics consider aborting a screening for mutations in BRCA1 and -2 to allfoetus carrying the HD-mutation difficult to justify, infertile couples opting for IVF, and offering PGD tobecause the child would have ‘many decades of good carriers [23]. This proposal (involving some sort ofand unimpaired living. Furthermore, the parents of selective population screening) raises a lot of prob-the child are not . . . affected in the way they would lems and questions. Obviously, such ‘wild’ screeningbe were the disease of early onset’ [20]. Others would be completely premature in view of the many


uncertainties regarding the penetrance of the various tive BRCA1/-2 testing (as a condition for validmutations in BRCA1 and -2, the psychosocial impact consent) has recently been presented by Geller et al.of such carrier screening, and the effectiveness of the [28] Let me just tick off some of the relevantvarious preventive measures (mastectomy, etc.). Fur- aspects. First, applicants should realize that thethermore, such screening may be a precedent for predictive value of finding a pathological geneoffering carrier screening for various (common) mutation is not established. Individuals with ‘causal’genetic disorders simultaneously. One of the prob- mutations may have variable expression of thelems of this so-called ‘multiplex testing’ is that it disease. In any case, recent studies suggest that thewould hardly be possible to provide clients with lifetime risks of mutation carriers are generally notadequate pre-test information – rendering the va- as high as previously suggested (just over 50% forlidity of any consent questionable. breast cancer, instead of 85%) [29]. Second, pre-test

information should not focus exclusively on medical(genetic) aspects. Information about psychological,familial, and social aspects is important too. It is

5. Preparing for the test especially important to inform applicants on possiblesocio-economic consequences. Clinical experience

5.1. Pre-test counselling has taught that many individuals at risk for a varietyof inherited late onset disorders are not aware of the

There is a strong consensus that predictive tests risk of insurance and employment discrimination ormust be accompanied by appropriate genetic coun- tend to underestimate these issues [18].selling. This principle has recently been adopted by The broadness and detail of information given tothe Convention on Human Rights and Biomedicine the applicant depend on the standard of disclosure[25]. The main purpose of pre-test counselling is to that is applied by the counsellor. In the ethicalsafeguard considerable deliberation and autonomous literature, three different standards are discerned,decision making. Counselling should include explo- namely the ‘professional practice’ standard, theration of all pros and cons of testing. Furthermore, ‘reasonable person’ standard, and the ‘subjective’counselling should elucidate the motives of applic- standard [27]. Only the latter standard requires theants for the test, helping the applicant to identify physician to disclose whatever information has rele-areas in which her /his expectations may be unrealis- vance to the decision making of the particulartic [26]. A real danger may be the so-called thera- subject, to take into account his specific information-peutic illusion, i.e. the belief that predictive testing al needs. Therefore, the subjective standard is bestguarantees early detection and/or prevention of tailored to fit the primary goal of the informeddisease. Informed decisions may also be endangered consent process, i.e. to enable subjects to makeby irrational pre-test perceptions of genetic risk. informed choices.According to a recent study, several applicantsstrongly believed they were gene carriers becausethey had the physical characteristics of the ‘affected 5.3. Time intervalside of the family’ or of an affected parent or sibling[13]. In view of the complexity of the decision con-

cerning submitting to presymptomatic genetic diag-nosis, informed consent may best be approached as a

5.2. Informed consent multistep process [28]. In general, it is desirable thatthere should be a substantial interval between the

The applicant’s authorization for the test should be giving of the pre-test information and the decisionintentional, substantially free (‘non-controlled’) and whether or not to take the test. This approach may,based on substantial understanding [27]. The pre-test however, not be realistic to individuals who applyinformation to be provided to applicants for predic- for the test after a long period of consideration.


6. Informing about the results of the test treatment of the disease in question is disclosed’[30].

6.1. Respecting the right not to know Obviously, handling concrete cases involves adelicate balancing of risks and harms.

The individual tested has the right to decide on How should this recommendation be applied to thefurther consideration that the result of the test shall context of genetic counselling for disorders like HDnot be given to him/her. (Such change of mind will and LFS, for which preventive and/or therapeuticoccur infrequently in case of adequate pre-test measures are not available or highly speculative?counselling.) While the international guidelines for pre-

symptomatic HD-testing stress the priority of theprinciple of respect for confidentiality, some authors6.2. Results should be given in personconsider breaching the duty to respect confidentialityto be justified, because it enables relative(s) to makeParticipants may be advised to bring a confidantean informed reproductive decision, thereby avoidingwith them to the result session.serious harm [5,31]. One may wonder, however,whether the invasion of confidentiality is justified in

6.3. Respecting confidentiality these cases. First, apart from the harm to the nextgeneration, there is nothing that can be done to avert

An adequate evaluation of this issue, requires to harm to existing relatives. Unsolicited informationdiscern between (at least) two categories of ‘third can easily result in serious psychosocial problems,parties’, namely doctors and relatives. which is at odds with the professional duty of non-

maleficence. Second, one may well doubt whetherDisclosure to relatives. Physicians occasionally feel breaching confidentiality would meet the conditionthe moral responsibility to convince the client to that ‘there is a high probability that . . . the discloseddisclose relevant information to relatives who could information will actually be used to avert harm’.benefit from that information or to grant permission After all, experience with presymptomatic testing forfor the physician to reveal this information. But what HD shows that carriers regularly take the risk thatif the client refuses to do so? The issue whether or they will transmit the mutation to the next genera-not to inform relatives at high genetic risk against a tion.client’s wish (or without his consent) is a difficult In the context of presymptomatic testing forethical dilemma because it poses a conflict between BRCA1 and 2 mutations, the case for giving prioritytwo well-known duties: the duty to preserve con- to the principle of confidentiality may becomefidentiality and the responsibility to warn third weaker when clinical experience shows that preven-parties of harm. Internationally, there seems to be tive interventions effectively reduce mortality andconsiderable support for the recommendation of the morbidity among carriers.President’s Commission: If the doctor holds the opinion that the principle of

‘ . . . confidentiality can be overriden . . . if and confidentiality can be overruled in some situations,only if the following four conditions are met: (a) this should be part of the informed consent process.reasonable efforts to elicit voluntary consent to Pre-test openness con tributes to the client’s well-disclosure have failed; (b) there is a high probability informed decision making regarding submitting toboth that harm will occur if the information is the test, and may avoid future moral conflicts.withheld and that the disclosed information willactually be used to avert harm; (c) the harm that Disclosure to doctors. The client should be involvedidentifiable individuals would suffer if the infor- in the decision whether or not to release informationmation is not disclosed would be serious; (d) appro- to other doctors, especially the GP. There is, how-priate precautions are taken to ensure that only the ever, no consensus on whether obtaining informedgenetic information needed for diagnosis and/or consent is necessary. Indeed, some persons argue


that it is sufficient to tell the client that the GP will are told to have prophylactic surgery or intensivenormally be informed, unless he (the client) refuses screening on the basis of physician bias rather thanto give permission (the ‘opting out’ approach.) fact [8]. I don’t know whether this is the same in

European countries. In any case, it is remarkable thatthere is a substantial inter-centre variation in the

7. Post-test counselling and evaluation percentages of carriers of BRCA-mutation who optfor surgery. In one Dutch centre, for instance, the

Any programme for predictive testing for her- majority (almost 60%) of these women opts foreditary cancers should be integral – i.e. it should mastectomy [34]. Representatives from some otherencompass (the offering of) post-test counselling, as centres, however, report that only a small minority ofwell as evaluation studies. carriers decide for this surgery.

Prophylactic mastectomy has caused commotion7.1. Post-test counselling in the media – some commentators emotionally

refuted such drastic interventions in healthy womenPost-test counselling serves various purposes. as ‘bad medicine’. This accusation may be ill-

First, psychosocial counselling can help individuals founded. After all, even though the efficacy of thisto cope with the test result. This may be useful for surgery still remains to be proven, there is real andcarriers as well as non-carriers. Some individuals realistic hope that it will substantially reduce mor-have profound difficulty accepting ‘negative’ bidity and mortality. Furthermore, one should respectBRCA1 results [13]. Illustrative is the case of a that carriers, in the face of a striking family historywoman who had seen many of her relatives die at an and close personal losses, may be unconvinced thatearly age, and who was convinced that she would screening (mammography, etc.) offers them theshare a similar fate. Because of this belief, she led a protection they disparately seek. It is not the (in-lifestyle characterized by excess use of alcohol and dividual decision to opt for) surgery as such whichdrugs. When told she was ‘negative’, she became needs ethical scrutiny, but the quality of the decisionsullen and could hardly believe this result. She said: making process. While prophylactic surgery is an‘I have wasted my entire life.’ accepted part of the management of some cancer

A second purpose of post-test counselling con- predisposition syndromes (eg, MEN 2a), discussioncerns the ‘medical management’. After all, the major of these options should be highly individualized inmotivation for offering and applying for predictive hereditary breast /ovarian cancer [32].testing is the hope that medical management follow-ing a ‘positive’ test result can help reduce cancer 7.2. Evaluation studiesmorbidity and mortality. The counsellor has theresponsibility to provide clients with adequate and Even though participation in research studies needbalanced information about the various options, and not be mandatory for all applicants (cfr Section 1),to help them to make a decision which best fits her discussion with carriers should emphasize the critical(his) own values and preferences. The client should research needed to evaluate the pros and cons ofrealize that the efficacy of the various prevention predictive DNA-testing and the efficacy of cancermodalities (cancer surveillance, prophylactic surgery, screening and prevention in individuals at high risk.hormone replacement therapy, chemoprevention, There are vital unanswered questions, both medicallifestyle modification) is currently unproven [33]. and psychosocial. What is the psychological impact

That the information provided is well-balanced, of predictive testing (in females and males, in adultscan, unfortunately, not be taken for granted. The and in ‘emancipated minors’)? What is the predictiveAmerican working group on predictive testing for value of a ‘positive’ test? What about phenotype–LFS is, for instance, unduly optimistic with regard to genotype correlations? Which (genetic and non-ge-the preventive value of lifestyle modification (e.g. netic) factors determine the penetrance and thenon-smoking) [5,6]. According to the American specific age of onset of the various mutations? Howgeneticist Weber, many carriers of BRCA-mutations effective is prophylactic surgery? What is the pre-


ventive value of screening and/or modification of education. Genetic illiteracy has been identified aslife-style (low-fat, high-fiber diets, regular exercise, one of the great obstacles for well-informed decisionetc.)? What about the function of the BRCA1/-2 making [38]. After all, how can technically complexgene products? Do BRCA1 and -2 act as so-called and emotionally charged information be explained to‘caretaker’ genes, which are involved in DNA repair ordinary people, many of whom never heard of DNA– and if yes, do defects in this DNA repair mecha- and barely of genes, who have hardly a clue aboutnism increase the risk of radiation exposure? [35,36]. probability, and whose education never equipped

In order to fully evaluate the presumed preventive them to make choices regarding these matters? Andvalue of certain modifications of lifestyle, it is how to guarantee that the doctors who counsel and/important that individuals comply and actually fol- or test individuals provide adequate genetic counsel-low the recommended ‘avoidance’ strategy. Continu- ling when doctors themselves have minimal traininging support and a regular reinforcement may be in genetics and sometimes fundamentally misunder-needed [37]. Such reinforcement can take various stand its basic principles? The main goal of educat-forms, amongst others rational persuasion and ma- ing the public is to promote well-informed decisionsnipulation. Rational persuasion is being employed if regarding whether or not to submit to genetic tests.the counsellor tries to influence the behaviour of the An important spin-off of such basic education is thatcarrier by causing him to consider and reevaluate his it will improve understanding of the content andintentions towards a certain act /behaviour, without implications of individual genetic counselling, there-bringing to bear any pressures or incentives extra- by enhancing it’s effectiveness.neous to the rational evaluation of the likely conse- Education with regard to human genetics and thequences of that act /behaviour from the perspective new genetic technologies should not be restricted toof the self-interest of the carrier [27]. While rational scientific and technical facts. Education of both thepersuasion is compatible with the principle of respect public and professionals should be integral, andfor autonomy, manipulation is not. should pay due attention to the psychological, societ-

al, and ethical aspects.

8. Concluding remarks

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Ethics of predictive DNA-testing for hereditary breast and ovarian cancer