Critical Reviews in Oncology/Hematology 40 (2001) 149–157

Ethical implications of genetic testing for breast cancersusceptibility

Antonella Surbone *Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

Accepted 30 January 2001

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150

2. Ethical implications of genetic testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150

3. Ethical implications of BRCA testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1513.1. Information and informed consent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1523.2. The right to be or not to be tested . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1523.3. The rights of others . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1533.4. Confidentiality and privacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1533.5. Discrimination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154

3.5.1. Discrimination in life insurance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1543.5.2. Discrimination by health insurance . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1543.5.3. Discrimination at the work place . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1543.5.4. Discrimination in the process of adoption . . . . . . . . . . . . . . . . . . . . . . . . 1553.5.5. Discrimination in the microenvironment . . . . . . . . . . . . . . . . . . . . . . . . . 155

3.6. BRCA testing in prenatal diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155

4. Philosophical implications of BRCA testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155

Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156

Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156

References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156

Biography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157

Abstract

The identification of gene mutations involved in hereditary breast cancer is a major recent scientific discovery, enabling us toidentify women at very high risk, and also providing the means to understand the biology of breast cancer and to explore novelpreventive strategies. Yet, it carries medical, psychological, ethical and social implications. This paper is a review of all the ethicalimplications of genetic testing for breast cancer predisposition, as well as an attempt to discuss the more philosophical questionsof women facing BRCA testing. To what extent does the individual benefit from genetic knowledge? Some women look withtrepidation upon the potential of planning their life in view of a risk, while others believe that only through knowledge andawareness we can improve control of our life. The risk of breast cancer may be qualitatively so important to justify all thepotential risks of finding out about it. © 2001 Elsevier Science Ireland Ltd. All rights reserved.

Keywords: BRCA; Breast cancer; Ethics; Genetics

www.elsevier.com/locate/critrevonc

* Present address: 1045 31st Street N.W., Washington, DC 20007, USA.E-mail address: surbonea@aol.com (A. Surbone).

1040-8428/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved.PII: S 1 0 4 0 -8428 (01 )00141 -X

A. Surbone / Critical Re�iews in Oncology/Hematology 40 (2001) 149–157150

1. Introduction

Ethics does not treat of the world. Ethics is a conditionof the world, like logic. Ludwig Wittgenstein, Note-book, 1914–1916.

Of the approximately 180 000 new cases of breastcancer developing each year in the US, 5–10% areconsidered hereditary. BRCA1 was identified as one ofthe genes associated with hereditary breast and ovariancancer [1], and its mutations confer an approximately50–80% life time risk of breast cancer. Such a discoveryis of major scientific value in itself and it may also shedlight on the biology of breast cancer and may promotethe search for novel preventive measures to reduce theimpact of breast cancer in general; but it also raisesmany dilemmas [2]. The initial report of the causalassociation between BRCA1 mutations and breast andovarian cancer susceptibility was followed by thecloning of other genes such as BRCA2 [3] and by theidentification of many mutations resulting in a trun-cated protein product which loses its regulatory func-tion [4]. The proteins made by BRCA1 and BRCA2play a critical role in enabling cells to repair their DNAwhen damaged, and their mutations lead to cancerundirectly, by disrupting DNA repair and by allowingcells to accumulate dangerous mutations. For the pur-pose of this paper’s discussion on the ethical implica-tions of breast cancer susceptibility screening, from nowon I shall refer to BRCA, without any distinctionbetween BRCA1 and BRCA2, and to breast cancer riskonly.

The gene penetrance varies with the particular muta-tions, and this impacts on our ability to accuratelyestimate cancer risk. Also, the information available atpresent is entirely derived from very high-risk families,and the possible gene penetrance in different contexts isunknown. The reliability of BRCA screening dependson prior probability of the condition, sensitivity andspecificity, screening techniques and number of muta-tions [4]. We are still far from a reliable screening test inthe general population [5], and the therapeutic optionsavailable at present do not afford complete preventionof breast cancer. Close follow-up should be mandatory,but the role of mammography in the detection ofBRCA associated breast cancers has not yet been estab-lished, particularly due to the young age of most af-fected women and the possible differences inradiosensitivity of BRCA-associated breast cancers [6].Life-style changes are certainly important in the preven-tion of breast cancer, and they should also be studied inthis setting. Chemoprevention is under investigationworldwide, and BRCA associated breast cancer mightdiffer in its behavior and response to treatments [7].

Bilateral prophylactic mastectomy is a drastic measure,which does not entirely protect from breast cancer, asclusters of breast tissue might remain after surgery [8].However, the test is now commercially available, andthe priorities now are: quality control to assure optimalsensitivity, specificity and efficacy of the test; propereducation of both the public and the medical commu-nity in understanding the limitations of such a screen-ing test; and recognition of the magnitude of thepsychological and ethical ramifications. The AmericanSociety of Clinical Oncology [9] provided guidelines toall oncologists in 1996.

The following discussion is not meant to underminethe relevance of genetic testing for breast cancer predis-position nor of genetics itself, but the focus is not onthe strictly scientific aspects. This paper aims at acomprehensive discussion of the social, ethical andphilosophical issues raised by BRCA screening. It isbased on a review of the original contributions to thisfield published around the time of the first identificationof BRCA mutations, as well as on the most relevantcontributions of more recent years. The primary goal ofthis article is to raise awareness, and it purposely leavesmany open questions: indeed the proper answer cannotbe given prescriptively in a paper, and it is rather foundthrough our common ongoing and active search for abalance between science and morality.

2. Ethical implications of genetic testing

The implications of genetics are not only medical andpsychological, but also social, political, ethical andphilosophical. Research is the pursuit of knowledge asmuch as a social enterprise, and because of this thescientific and ethical debate must proceed together. Theethical implications of genetics have been extensivelytreated in the literature as part of the Human GenomeProject, and the fundamental themes identified [10] aresummarized in Table 1 in the form of open questions.

The first two — which genetic information is gener-ated and who controls its use and dissemination — areclearly related to power and science. Knowledge isnever neutral, it is always ’situated’: we produce acertain knowledge in a certain context under the influ-ence of a certain political and intellectual pressure, andwe use this knowledge for certain purposes. For in-stance, the consensus about whether genetic testingshould be limited to pathologic entities for which pre-ventive or therapeutic measures exist and about whatconstitutes ‘therapeutic’ is reached not only within thelimited frame of medicine, but primarily on the basis ofcultural, social and political standards [11].

The third question — which genetic procedures areallowed — brings us closer to the direct responsibility

A. Surbone / Critical Re�iews in Oncology/Hematology 40 (2001) 149–157 151

Table 1Fundamental ethical and philosophical issues in genetics

Which genetic information should be generated?Who controls its use and dissemination?Which genetic procedures are allowed?How is genetic normalcy defined and by whom?How does genetics change lives?Does genetic knowledge expand our control on life?

cancer? Someone will answer all these questions:whether it is the political elite or society in its entiretystrongly depends on our personal engagement.

The last question — does genetics expand our con-trol on life? [17] — is best answered after considering inmore detail the ramifications of BRCA testing.

3. Ethical implications of BRCA testing

Table 2 lists the specific ethical issues in testingwomen for BRCA1 or BRCA2 mutations. Differentgenetic-related diseases share most scientific aspects,such as their multifactorial nature, resulting from acomplex interplay of genetic and environmental factors.Most ethical aspects are also common to all genetictesting, including fundamental issues of justice in theavailability of the test and of distributive justice in theallocation of resources. Also, common to all genetictesting is the interference of major economical interestsin the development and in the commercial promotion ofcancer screening tests, as well as in the establishementof public health priorities [18].

The uniqueness of BRCA testing lies first in thatBRCA1 and BRCA2 differ from genes with higherpenetrance, where the ethical issues relate to certaintiesmore than to risks. Genetic knowldege differs fromother types of medical knowledge for its individual,predictive, and probabilistic nature [19]. This is particu-larly true in the case of BRCA, where penetrance isrelatively low and the impact of allele-specific pene-trance has not yet been extensively studied. Second,breast cancer is a common disease whose incidence isincreasing and at earlier ages. While most of this phe-nomenon is explained by screening mammography andthe increasing detection of DCIS, breast cancer is nowperceived by the public as an ‘epidemics’ [20]. More-over, breast cancer is a fundamental and symbolic issuein women’s health care and many political battles cen-ter around prevention, early diagnosis and treatment,access to research and to screening programs allwomen. Finally, the suffering and death frommetastatic breast cancer are devastating and theirspecter is incumbent on any BRCA positive woman.Being tested for a BRCA mutation has profound and

of the scientific community. Science meets the needs ofsociety and contributes to their creation: to what extentgenetic manipulation will be permitted depends on so-cial and political decisions first, but scientists determinethe conditions for the feasibility of such geneticprocedures.

The next two questions — how is genetic normalcydefined and by whom and how does genetics changelives — appear to shake our true foundations. Byknowing our genome, we face genetic diversity and,with it, the risk of ‘geneticization’, the identification ofpersons with their genes [12,13]. Geneticization is thewidespread tendency to overemphasize the role of genesin disease causation, in medical practice and in socialattitudes toward disease. Geneticization stems primarilyfrom a deep misunderstanding of genetics, which on thecontrary reveals more similarities than differences inour genome (all living organisms share 80% of theirgenome, and humans differ from one another for onlyless than 0.1% of their genome!) Moreover, if we realizethat diversity, whether genetic or not, is ‘completelycompatible with human equality, we have little incen-tive to misuse genetic data’ [14]. Still, genetic diversitychallenges our definition of normalcy and of health.Are we scientifically entitled to privilege genotypic overphenotypic information? Who is in charge of definingnormal and healthy in view of the new genetic informa-tion? Disease is not only a pathologic entity: disease isalso a social construct, almost inevitably accompaniedby a change in the ontological status of the ill person[15]. The change which occurs when the symptom expe-rienced is labeled as a disease (for instance, when thepatient goes from experiencing fatigue to havingleukemia) is likely to happen now on the basis ofgenetic information. Will we be healthy if we are ingood health or if we do not carry a predisposition to amajor (or minor!) disease? If we do carry such predis-position are we going to be sick? If not, do we fit intoa new category of the ‘asymptomatic ill’ [16]?. And whowill make the determination? How is this going toaffect our lives? Will the concept of responsibility, forinstance, change on the basis of genetic information? Italready happens in courts: will it happen in our dailylives? Will our efforts at improving the level of educa-tion or at keeping a safe environment decrease once weknow who is genetically predisposed to be a brightstudent or to be susceptible to heavy metals or to

Table 2Ethical implications of BRCA testing

Information and informed consentThe right to be tested or notThe rights of othersConfidentiality and privacyRisk of discriminationConsequences of prenatal diagnosis

A. Surbone / Critical Re�iews in Oncology/Hematology 40 (2001) 149–157152

unique psychological effects, which have now beenextensively studied and reported in the medical andpsychological literature. In response to the wide arrayof psychological reactions to breast cancer suceptibilitytesting, proper counseling is needed to address theanticipated and actual emotional reactions to the testresults [21], as well as to assess the often exageratedbreast cancer risk perception of many patients, whichcan either negatively affect their compliance to follow-up programs or foster an unjustified willingness toundergo prophylactic surgery [22].

3.1. Information and informed consent

Genetic information is necessarily imprecise for itdeals with probabilities and risks: it can therefore beeasily manipulated, especially under social pressure [11].Far-reaching educational programs are needed, andthese are the responsibility not only of the scientificcommunity, but also of the mass media. Moreover,specific policies should be instituted to protect thoseindividuals who would not benefit from education, suchas children and the incompetent.

For competent adults, informed consent is the abso-lute prerequisite for any genetic testing, and it shouldnot be limited to the technical and medical aspects ofthe test, but it should also include discussion of itssocial and ethical implications [9]. As part of geneticcounseling [23], informed consent should provide theperson with detailed accurate comprehensible informa-tion about all aspects involved in breast cancer suscep-tibility screening.

The ethics of informed consent, based upon theprinciple of patient autonomy, is well known. Informedconsent must be an ongoing process fostering patients’freedom. However, it is neither a substitute for theprofessional responsibility and accountability of thephysician [24], nor a solution to all ethical issues in-volved in genetic testing. Countries notoriously differ intheir attitudes towards truth-telling and genetics maynot be an exception. While genetic information willlikely be handled differently throughout the world, thisis a time to foster a higher respect for patient autonomyespecially in those countries where it has been tradition-ally underestimated.

3.2. The right to be or not to be tested

Most of today’s debate surrounding genetics isframed in the language of rights. Following the policyadopted in most cultures of non-directive genetic coun-seling — based on respect for the person’s autonomyand on the right to self-determination — the choice ofwhether or not to pursue genetic testing is left to theindividual. Such a standpoint inevitably implies themore or less explicit aknowledgment of a ‘right not to

know’ [9,25]. This right, however, has been also seen asa ‘right to genetic ignorance’ and strongly opposed bysome arguing in favor of autonomy itself (for self-deter-mination to be possible, information is needed) and infavor of the importance of social bonds, such as familyrelationships (which can create an obligation to seekgenetic information, because it is useful to others) [26].In no way is therefore the ‘right not to know’ a given inthe present ethical debate. Yet, the position of thispaper is that, following an essential principle of civilliberty, the right to undergo genetic testing should bestrictly observed. However, this gives rise to severalother problematic aspects. First, is genetic testing forbreast cancer susceptibility a right for each woman or isit a right only for those belonging to high risk-families?The test is presently not indicated for mass screening[9,18], it is very expensive and time-consuming, and thepublic tends to overestimate the low predictive powerof BRCA testing in low-risk women. Thus, there isample debate on whether or not BRCA testing shouldbe offered to any person (men can also be carriers ofBRCA mutations) requesting it, or whether testingwould be best restricted to high-risk groups. At present,the answer to this dilemma is uncertain, as private andpublic benefit may not always coincide, and the rightsof the individual may go beyond established scientificcertainty. Unfortunately, this opens the doors to thepossibility of major economic speculation, as well as tothe possible detrimental consequences for the individualoutside high-risk groups, whose test is performed with-out accurate knowledge of its predictive power.

Second, who has rights to archived materials?. If thesubject is alive, his or her consent should be obtained.But what if the subject is dead? Most countries are nowestablishing regulations to limit genetic testing to thepurposes intended at the time of informed consent [25].This policy stems from considering body parts as aproperty of the subject, a concept with major ethicaland legal consequences, including organ donation,financial aspects of the ownership of one’s body [26]and right to euthanasia [27]. On the contrary, it goesagainst a widespread policy of considering samples asthe property of laboratories, once analyzed — a policywhich has greatly helped epidemiology research in thepast. Once again, the debate is very intense, anddifficult to resolve.

Finally, the right applies to the results of the test, andeach person is entitled to obtain the results or not to.Now that the test is commercially available, we have todecide who first receives the results, whether it is thepersonal physician, or the laboratory. Then we need toassure that this entity (hopefully a person) will notdisclose the information, unless it has been clearlyestablished that the tested subject wishes to know theresults, that nobody else receives them instead and thatunexpected results — such as chromosomal abnormali-ties or non-paternity will not be disclosed.

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3.3. The rights of others

Whether or not the language of rights is the only orthe best frame to discuss ethics (a subject for philosoph-ical inquiry), we face many more issues of rights ingenetic testing. As previously stated, the standpoint ofthis paper is that the right to undergo genetic testing isstrictly individual. However, with BRCA mutations wehave a severe, often devastating and lethal diseasewhich can be vertically transmitted. Do others haverights? Does the daughter of a cancer patient have theright to know her mother’s BRCA status? Does amember of a high risk family? Physicians are dailyconfronted with difficult situations where a balancebetween autonomy, beneficence and justice is not easilyreached.

Does anyone have the right to ask someone else toundergo BRCA testing [26]? We all know that if theindex case is analyzed and found to have a mutation,testing for the rest of the family is easier and likely tobe more reliable. We can therefore expect such requeststo take place. Do parents have a right to test theirdaughters? Research shows that genetic testing of chil-dren has profound psychological repercussions on thefamily dynamics, and is often not to the advantage ofthe child at risk [28,29]. Finally, does the researchcommunity have any right in asking for the test, inperforming it on archived material or in conductinganonymous research? Here we might observe howdeeply eroded is the concept of trust in medicine and inscience. Since doctors often failed to meet their ethicalobligations towards patients and often favored theirpersonal benefit, whether economical or related to pres-tige, trust has lost its proper place in medicine and it isvery difficult to restore it [30].

Determining who has rights stems from broad con-siderations of us as individuals and us as a community.The language of rights is centered around the principleof personal liberty, whereby one can pursue any rightprovided it does not interfere with the rights of others.At stake here is indeed whether we are only au-tonomous independent individuals or relational individ-uals connected to one another. In the US familieswhich were dispersed are now getting together to facetheir genetic risk, and this is symptomatic of a newawareness of our connectedeness, which genetics bringsto us. This is however not only limited to the familyunity, and genetic knowledge may indeed foster a senseof expanded community [31].

3.4. Confidentiality and pri�acy

Confidentiality and privacy are of paramount impor-tance in genetic testing. Not only do they directly relateto the possibility of discrimination, but they are centralto liberty and autonomy. The issue is whether civil

liberties should bend in the face of other considerations,such as public health concerns or a higher good to beachieved [32]. Genetic testing seems to belong to thesecond category, and less confidentiality and privacymight be justified in view of a higher benefit for theindividual tested, and not for society: in other words,this would not be a utilitarian manoeuver. In fact, forBRCA mutations there is no horizontal transmission,which makes it quite different from the case of HIVtesting (though much can and should be learned fromthat experience). Many women, while aware of the riskof possibly losing their insurance and even their jobsdue to lack of confidentiality, consider such possibilitiesalmost irrelevant by comparison to the risk of breast orovarian cancer. Whether or not this attitude is justifiedin view of the present medical limitations, society mightarrive at determining that knowledge of genetic infor-mation is so useful that it should prompt us to recon-sider some ethical and legal principles.

Certainly the Hippocratic respect for confidentialityand privacy is not likely to survive intact the era ofgenetic testing, computerized information and privateinsurance. Already there is a disturbing amount of databases where health information is collected and stored,at least in the US [32]. Keeping confidential geneticdata would still imply maintaining some records. This isan inevitable reality in modern societies, but is alsounfortunately symptomatic of a categorizing and la-belling which goes beyond health care needs and ishighly functional to maintaining power [33].

Clearly these issues are of extraordinary proportionsin those countries where there is no social medicine andthe health care industry dictates far too many rules. Ifthe cost of the test is covered by the insurance there isno hope for its results to be kept confidential. Nor isthere much hope for privacy to be respected by employ-ers. The only solution seems to be restricting theavailability of the test to research settings, where therewould be no cost for the patient and the informationcould be handled confidentially. But this option raisesother concerns, and primarily it goes against a basicprinciple of equality. Why should women who haveaccess to research centers be privileged? The officialposition of ASCO, in consideration of this element,supported testing also outside research settings [9].Also, even women followed in research centers mightnot obtain insurance coverage for the cost of availableprevention. Moreover private institutions already offertesting for particular mutations to any interestedconsumer.

Finally, respect for confidentiality and privacy has tobe seen in view of the repercussions that genetic testingfor an autosomal dominant trait has on others, aspreviously discussed. However difficult, though, physi-cians should continue in the Hippocratic tradition andmaintain impeccable standards with respect to confi-dentiality and privacy.

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3.5. Discrimination

Although the scientific community is aware of themultifactorial nature of all diseases and of the role thatenvironmental and other factors also play in geneticdisorders, cases of discrimination based solely on ge-netic predisposition have been reported [16] and BRCAmutation carriers are at risk (Table 3). Fear of geneticdiscrimination on the basis of a positive BRCA resultcan be a powerful deterrent to undergoing breast cancersusceptibility testing, as shown in surveys of experts ofthis field [34] and of women considering genetic testing[35].

It should be first stressed how campaigns againstdiscrimination might fail to unmask the discriminatoryprocess itself [36]: by defining a norm from which onedeviates, we define a standard, an ideal. Much likewhen we say that white people and black people areequal, or that men and women are equal, we often failto unmask that whites and men are the paradigm, towhich blacks and women are compared. The real aimof our social engagement should not be to win adiscrimination battle per se, but to strive for trueequality.

3.5.1. Discrimination in life insuranceThis varies in different countries. According to a

1996 survey [37] no laws restricted life insurers fromrequesting genetic testing in the US. In Belgium, Aus-tria and Norway requesting a genetic test or its resultswas banned. In the Netherlands life insurers couldrequire a genetic test for policies above a certainamount of money. Italy, Germany, the UK, Spain,Portugal and Japan had no regulations on the matter.

3.5.2. Discrimination by health insuranceThis is a major problem for those countries relying

mostly on private health care. Based on the rationalethat genetic predisposition constitutes a pre-existingcondition, health insurance can be denied with thealleged justification that adverse selection could occurand that the health insurance industry operates on theprinciple of actuarial fairness. The policy of underwrit-ing, according to the industry, is fair in spreading therisk among a large cohort while putting a financialburden on those who are expected to make excessiveclaims [38]. However, actuarial fairness is not moral

fairness [39–41], and the result is that those who mostneed health coverage are deprived of it, and womencarriers of a BRCA mutation might be among them[42]. The implications of present research in genetictesting for susceptibility to breast cancer may be sofar-reaching in the future to make today’s debate aboutinsurance seem relatively trivial. At present, however,some claim that no long-term alternative to consensualdiscrimination exists, while others believe that universalaccess to health care would certainly be one. It is clear,once again, that the proper answer goes beyond science,and involves broad ethical and political considerations.

In the US some states prohibit genetic testing and theuse of genetic information for health insurance [37],based on the following rationale: that informationabout predisposition to a disorder is not the same asmedical history; that people should not be denied in-surance for a problem for which they are not responsi-ble; and that the insurance industry does not know howto handle genetic information, and this may deter peo-ple from undergoing an otherwise desired test or forceothers to know results against their will. It is notewor-thy that the true issue, i.e. that genetic risk never existsalone (the false premiss of any geneticization) and mostdiseases result also from environmental factors [41], israrely offered as a reason for protecting againstdiscrimination.

Thus, BRCA mutation carriers might be denied cov-erage for the cost of the test and treatment. Moreover,where medicine is not socialized, the insurance industry(i.e. economical pressure) might dictate or influencedecisions regarding prevention: is prophylactic mastec-tomy less expensive than follow-up and possible treat-ment of breast cancer in a 25 year old woman? Finally,the risk of discrimination will be vertically transmittedto the daughters, and this dramatically increases wom-ens’ concerns for discrimination.

3.5.3. Discrimination at the work placeThis can occur as a result of a positive genetic testing

[16] and much debate surrounds its legitimacy. Mostindustry claims that ‘differentiation’ should be allowed,while some argue in favor of applying strict criteria tojustify genetic screening programs by employers [43],such as strong evidence of a causal relationship with thework environment, hazard to the subject or to thirdparties, safeguards to employees and insufficient reduc-tion of the risk by reasonable measures on the employ-er’s part. However, the only correct solution toprofessional hazard is systematic and effective environ-mental control: genetic testing is not an alternative.

In the US the legislation does not specifically protectagainst genetic discrimination, and although there isgrowing effort at establishing new regulations [44]women may be discriminated against in their jobs iftheir life time risk of breast cancer is 80–85%. Indeed,

Table 3Risk of discrimination for carriers of BRCA mutations

In life insuranceBy health insuranceAt the work placeIn the process of adoptionIn the microenvironment

A. Surbone / Critical Re�iews in Oncology/Hematology 40 (2001) 149–157 155

this may be another form of gender based discrimina-tion [17].

3.5.4. Discrimination in the process of adoption [16]This may also occur, since no regulation exists and

longevity is a criterion for adoption in many countries.The idea that a woman might be a worse motherbecause she develops breast cancer, strikes as incrediblyunjust. Moreover adoption could indeed be the pre-ferred choice for couples with a genetic risk. Medicalorganizations should provide updated information onthe legislation and an ongoing system of references andreferrals for those patients who encounter discrimina-tion at any level. Other issues surrounding adoption,such as the possibility that adoptees be carriers of aBRCA mutation, and that they may wish to learnabout their genetic background, may also lead todiscrimination.

3.5.5. Discrimination in the microen�ironmentThis is a final more subtle form of discrimination.

This is where the carrier woman might find herself lesswelcome as a possible wife or as a possible mother. If aduty to genetic testing prevails [26], a woman might beasked to undergo testing before being married, or totest her fetus when pregnant. Only women’s strongpersonal and political engagement may provide someprotection against discrimination in themicroenvironment.

3.6. BRCA testing in prenatal diagnosis

Genetic testing for BRCA mutations is feasible in theprenatal setting, leading to important consequenceswith respect to abortion and eugenics [45]. Abortion isa moral quandary faced by many women in their lifeand it must be a safe medical procedure [46]. Thechoice of an abortion based on genetic testing posesparticular problems [47] and involves the physician in aspecial way [48]. It is through genetic counseling thatthe woman and the couple learn about genetic predis-position, and it is through society and political choicesthat the acceptance of disability and disease is deter-mined. Traditionally genetic counseling has been non-directive to leave reproductive choices up to theparent(s) and avoid eugenics. There are, however, caseswhere women have been forced to have abortions offetuses at risk in order to spare the ‘economical burden’on society [16]; a practice morally disgusting.

In the case of BRCA mutations, the carrier statusimplies a high risk of developing breast cancer in afemale; yet it is still only a risk [49]. Moreover thedisease will not manifest for at least 20 years and it iscurable when diagnosed early. Today’s positive fetusmight benefit from diagnostic and therapeutic progressin the future. While the final choice rests with the

woman, who might have witnessed many of her rela-tives dying of breast cancer, she should not be deprivedof an optimistic outlook. Maintaining the non-direc-tiveness of genetic counseling remains, however,strongly needed to prevent eugenics.

Eugenics is primarily a political and cultural risk andthe contribution of genetics should not be overesti-mated. Coercive eugenic is a major and unfortunatelywell known risk of totalitarianism [50], but more subtleforms of backdoor and ‘homemade’ eugenics are veryworrisome too [47,51]. Sex selection, for instance, is toooften justified on the basis of autonomy, as does selec-tion of other characters including abnormal ones.These, however, are always the result of a coerciveculture, even when apparently following a free individ-ual choice, and are profoundly unethical [52]. More-over, eugenics can stem from increasing economicalpressure in health care [53].

4. Philosophical implications of BRCA testing

The extensive ethical implications of breast cancersuceptibility screening should not prevent women fromopting to be tested, nor should they halt the ongoingresearch in this field. There are steps we can undertaketo minimize the negative social and ethical repercus-sions of BRCA testing, and some are listed in Table 4.

We might also redefine our position with respect towhen a test is indicated and conclude that the informa-tion obtained is beneficial, in spite of the medicaluncertainties and of the social repercussions. While amedical consensus has not yet been reached, indeedmost women at risk view it as such.

There is, however, another level, even deeper, wherebreast cancer susceptibility screening affects us wherewe encounter some pressing unanswered questions: cangenetic knowledge affect our concepts of diversity andof responsibility? Is the risk of discrimination increasedby already existing gender biases? Does genetics affectour views on autonomy and trust? And, finally, doesgenetic knowledge increase control? [17] These ques-tions belong to ethics and science, but go beyond themand reach the philosophical level.

Table 4Ethical and social implications of BRCA testing: what can we do?

Assure quality control on breast cancer suceptibility testsUnderstand the ethical and social ramifications of BRCA testingDiscuss openly with the publicProvide ongoing accurate information to the patientsBe the patients’ advocates if discrimination arisesBe sensitive to individual differences in the perception of riskRespect individual beliefs and prioritiesUnderstand the philosophical implications of BRCA testing

A. Surbone / Critical Re�iews in Oncology/Hematology 40 (2001) 149–157156

Clearly, we are not our genome: yet we culturallytend to see genetic data as more fundamental and moreinalterable than any other in the equation of life. Eventhough this is true only in a small part and geneticshelps us very little in predicting our future, by so doing,to what extent does genetic knowledge expand ourcontrol on life? And even further: can genetics limit ourcontrol on life by paralyzing our decision-making pro-cesses or by shedding a dim light onto them? Howmuch do we equate genetic knowledge with fate? Beforewe offer the test and provide appropriate counseling,we should ask ourselves the fundamental philosophicalquestion: to what extent do we benefit from anticipa-tion of the future. The answer to this question lies atthe foundations of our being. It is essential that weventure there if we wish to be honest and helpful withour patients.

Finally, genetics and its dilemma are exclusive ofcertain societies. Issues of poverty and malnutrion, ofchildhood mortality, of infectious disease epidemics, oflack of basic medical support are the reality of far toomany other societies and deserve our scientific, ethicaland political efforts as well. Thousands of years agoalready the Chorus in Antigone used to sing: ‘Futurethings: not our domain. But in this today which unrav-els in front of us, what shall we do?’ Genetics providesno answer. We must provide the answer and it shouldbe morally and politically just.

Reviewers

Dr Alberto Costa, Fondazione Salvatore, Mauguri,Divsione di Chirurgia Generale e Senologia, Via Fer-rata, 8, I-27100 Pavia, Italy.

Professor Andre-Pascal Sappino, Head of the Divisionof Oncology, University Hospital of Geneva, CH-1211Geneva 14, Switzerland.

Gianni Bonnadonna, Istituto Nazionale Tumori, ViaVenezian 1, I-20133 Milano, Italy.

Professor H.-J. Schmoll, Martin-Luther-UniversitatHalle-Wittenberg, Klinik U, Poliklinik fur Innere Medi-zin, Hematologie/Onkologie, Ernst-Grube Strasse 40,D-06120 Wittenberg, Germany.

Acknowledgements

This paper is dedicated to Francesco Akira and to allthe women who shared with me their fears and theircourage.

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Biography

Dr Antonella Surbone graduated from the Universityof Turin, Italy in 1982 cum laude. She is Board certifiedin Medical Oncology and in Infectious Diseases. Shetrained at the Istituto Nazionale Tumori, in the Divi-sion of Dr Gianni Bonadonna. She practiced medicaloncology in Italy and in the US, where she was ClinicalAssociate at the National Cancer Institute in Bethesda,MD and Associate Attending Physician and Member atMemorial Sloan-Kettering Cancer Center in New York,NY. She has a degree in ethics from the University ofRome, Italy and she has studied philosophy at Ford-ham University in New York, NY.