Medicina e Morale, 3 (1999)

Antonella Surbone^*, The ethical challenge of genetic testing for breast cancer
 

*Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering, Cancer Center, New York.

The identification of Brca11 and Brca22 as the genes associated with some hereditary breast and ovarian cancers has major scientific value, but also raises many dilemmas.³Genetic testing for Brca mutations has no value in general screening, and it is most often uninformative even in women with high-risk families.⁴Its ability to predict the development of cancer in mutation carriers is still under evaluation,⁵and available treatment options - such as lifestyle changes, close follow-up, chemoprevention, and even prophylactic surgery - do not yield complete protection against breast and ovarian cancer.⁶Despite these major limitations,⁷the test is now commercially available. Most often the public is mislead by the press raising false hopes for effective prevention, and thus tends to perceive genetic testing for breast cancer as a reliable screening tool. Therefore, major educational efforts are needed for lay people as well as for health-care workers.

As part of the Human Genome Project, extensive debate has surrounded the social and ethical ramifications of genetics⁸and these have been acknowledged in recently published guidelines for health care workers.⁹The most pressing issues presently are: information and informed consent;¹⁰rights in access to genetic information¹¹- including rights of the person tested (and whether or not testing should be limited to high-risk populations only), rights to know the results of someone else's test, rights to have a fetus or a child tested,¹²rights of the research community to use archived material from deceased patients or to process samples for anonymous research;¹³privacy¹⁴and confidentiality - including the privacy interests of the deceased - risk of discrimination in health insurance, at the work place, in adoption and possibly in access to education;¹⁵prenatal susceptibility testing¹⁶- including counseling, abortion, embryo selection¹⁷and eugenics;¹⁸and justice in the allocation of resources - both in the Western context and in a worldwide perspective that includes less affluent areas. Despite ample debate in the medical and ethical literature,¹⁹most of these issues are still unresolved: this illustrates the complexity of the subject, and leaves us with the unsettling conclusion that, as the secrets of our genome unravel, something more fundamental is at stake, which we have not yet fully explored. In analyzing many dilemmas of women who consider genetic testing for breast and ovarian cancer, it clearly emerges how medicine, culture, normativity and philosophy are complexed. It is such connection which needs our attention. The scope of this paper is to illustrate this thesis, by exploring some recurrent themes of the discussions with my patients who consulted me not as a genetic expert, but rather as their treating oncologist. In those conversations patients were openly expressing their concerns for themselves and their female relatives in the context of a well-established patient-doctor relationship. Fascinated by the complexity of the issues raised by my patients, I took notes and later organized them in five recurrent main themes, which I present here in the format of open questions. Can genetic knowledge affect our concepts of diversity and responsibility? Is the risk of discrimination increased by gender biases? Does genetics affect our views on autonomy and trust? Does genetic knowledge increase control? Rather than pretending to give an answer to such questions, this paper wishes to stimulate the moral debate which is central to solving the dilemmas of genetics, in Rilke's spirit of 'loving the questions first'.

Can genetic knowledge affect our concepts of diversity and responsibility?

Philosophers have long considered the nature of knowledge: knowledge is never neutral, never abstract from the 'knower' and from the context. Knowledge is rather always 'situated', for it is produced by an individual in a specific context.²⁰In addition, knowledge is instrumental: a means to enhance our ability to control the world. Knowledge has an epistemic, a pragmatic and an ethical dimension, which are always intertwined since it is not possible to think profitably about cognition without thinking about practice.²¹This applies particularly to science, which is not only the abstract pursuit of 'truth', but primarily a social enterprise never independent of its applications and their consequences, nor of the context.

Genetic knowledge differs from other types of knowledge, insofar as it is predictive, probabilistic and individual.²²Thus, in genetic knowledge the practical and contextual aspects assume a unique and peculiar relevance.

The interplay of scientific and social issues is particularly manifest in the heated debate on genetic manipulation, where the social and political consequences and the moral implications are strikingly apparent. Yet the more subtle dilemmas of genetic testing are equally important to uncover and to analyze. When women ask: 'Is testing worthwhile if there is no guarantee of effective prevention?' they raise complex epistemic and ethical questions. The more traditional medical view holds that a test should be performed when some forms of therapeutic intervention is available; otherwise a medical test is not offered outside of research purposes. With respect to genetic testing, however, there is no consensus now on whether or not should genetic testing be limited to pathologic entities for which preventive or therapeutic measures exist. This is due to our lack of a proper definition of what is 'therapeutic' vis-à-vis the novelty of genetic knowledge. In the case of genetic testing for Brca1 and Brca2 mutations, for instance, sensitivity, specificity and reproducibility are sufficiently high to provide accurate information regarding what the test purports to measure -the presence or absence of certain mutations. However, the ability to predict the future development of breast and ovarian cancer is still uncertain, particularly when considering the impact of allele-specific penetrance.²³In other words, genetic testing for breast and ovarian cancer predisposition provides us with an accurate, yet only probabilistic information. Hence, the determination of the worth of the test stems primarily from a social agreement between test subjects, the research community and society at large on 'what is worth', and this may be found outside the limitations of immediate therapeutic results. For the research community, for instance, the test is worthwhile even in the absence of direct therapeutic benefits because, through the study of Brca-associated cases, the biology of breast and ovarian cancers can be studied and better understood.²⁴Also among test subjects, some persons value the possibility to make more informed choices about their health so highly, that the test appears worth even in the absence of definite prevention strategies. This illustrates how genetic information may carry benefits to the individual and to society, which go beyond those contemplated in traditional medical dogmas. To face genetic knowledge and its dilemmas, a new conceptualization of the world is required, which challenges our traditional epistemic approach to science and medicine.

Genetic knowledge relates to genetic diversity, and carries the risk that people will be identified with their genes, if misleading and excessive weight is given to the predictive value of genetic information. This process of identification of human being with their genome is know as "geneticization", whereby genetic models are increasingly used to explain disease and thus influence drastically the medical practice as well as individual and societal attitudes towards a broad spectrum of issues (from reproduction, to prevention, to disease control to exquisitely moral issues).²⁵Here again the scientific and the social levels overlap. In fact, it is through the research community that we know our genome and face genetic diversity, but it is through society that we attribute values. Society colors the meaning of normalcy and diversity. Society at large - hence all of us - often attaches a negative connotation to diversity and determines the acceptability of sickness and disability. Disease has both an objective and a subjective dimension, and has both a 'meaning' and a 'value', which are established through social agreement. Disease is not only a pathologic entity: disease is also a social construct, at times accompanied by a change in the "ontological status" of the ill person.²⁶Suffice to consider what happens when the symptom experienced (fatigue, for instance) is labeled as a disease (the flu versus a form of leukemia). In the genetic era, this ontological change may happen on the basis of genetic information alone. When our genome is known, will we be 'healthy' if we have no organ dysfunction or only if we do not carry a predisposition to a disease? If we do carry such a predisposition are we going to be called 'sick'? Will we rather have to fit into a new category of the 'asymptomatic ill' and what would this exactly entail? (May we be reminded that certain groups of people such as Hiv positive persons are already part of such category). How will genetic diversity affect the lives of those who carry a genetic predisposition to cancer and those of their relatives? Clearly, how genetic risk is perceived depends both on how society faces diversity and on how the scientific community will deliberate as to whether genotypic or phenotypic information should be privileged. If society accepts diversity as an objective element of life, and hence 'normal', there will be 'little incentive to misuse genetic data'.²⁷However, there is something that distinguishes genetic from other types of diversity: its apparent inevitability, as both the personal and the social consequences of it seem to escape from our control. Mystery surrounds genetics in our collective imagination, and makes us perceive genetic risk as more drastic than others in life. Recognizing that genes never act alone is the first step to put genetics into proper perspective. Cancer is a polygenic genetic disorder involving the interaction of many genetic mutations and multiple - largely still unknown - environmental cofactors. Brca1 and Brca2 mutations are only two factors for the population at risk for breast cancer, and they may turn out to be among the least important. This is already the case in the general female population (the role of Brca1, and Brca2 mutations being proven only in high-risk families, where pedigrees show a high incidence of first and second-degree female relatives affected at early ages by both breast and ovarian cancers). Thus the recommendation for genetic testing for breast cancer as a screening tool in the general female population is misleading if not fraudulent at present; while even its recommendation in high-risk families outside of research studies may still be premature (and pedigree analysis may remain more meaningful). The whole scientific community - including basic scientists, health care workers, pharmaceutical industries, scientific and medical press - thus has the primary responsibility to study the interactions of genetic and environmental factors and to clarify the proper role of Brca testing.²⁸Media also play a major role in the education of the public, and the public itself has a responsibility to seek accurate information. Because of the profound resonance that misleading information in the field of genetics can have on all our lives, we are reminded of how much humility and sense of proportions is required in medical research as well as in the dissemination of medical information.

The various but limited roles of genes in disease causation suggest that responsibility towards our genes does not differ from health-related responsibility as we presently see it. In fact, it is from the balance - or lack of - in attributing the proper place to genetic and environmental factors that the answer to a major question can be found. The question is: do we - as members of society - have any special responsibility because of genetics? There is no additional responsibility that we owe to society because of our genome, since genetic diversity in no way changes our positions in society. Hence, any form of eugenic pressure should be strongly opposed. Moreover, we remain responsible to care for ourselves, our community and our environment. A test for intelligence, or susceptibility to heavy metals, or predisposition to breast cancer is not to be used for discriminatory purposes or as a shortcut in our responsibility to further education, keep a safe environment, and research the cofactors involved in disease causation.

Is the risk of discrimination increased by gender biases?

If we fail to understand properly the meaning of genetic diversity, discrimination will easily arise from genetic knowledge. Cases of discrimination based solely on genetic predisposition have been reported in the medical literature. Legislative efforts to protect against genetic discrimination have been made in the United States and worldwide,²⁹often to go beyond the mere litigation of particular cases. The issue of discrimination, in fact, can not only be addressed on the level of individual cases in legal proceedings and the fight against discrimination should address the discriminatory process itself.³⁰If we consider the possibility of discrimination against women who test positive for Brca1 and Brca2 mutations, it is clear that the successful strategy is to foster true equality at a societal - not only legal - level.

Women are still often exposed to gender discrimination. As cancers associated with germline Brca1 and 2 mutations are predominant (though not exclusively) in women, there is justified concern that discrimination against a female heterozygote carrier will be enhanced by gender biases. It is noteworthy that men can also be carriers of Brca1 and Brca2 mutations and transmit them to their offsprings, but somehow this is rarely the subject of public discussion and awareness. This contributes to enhance the gender bias associated with such mutations.

In considering genetic testing, therefore, women's attitudes differ with respect to the relevance that they place on the risk of discrimination. Members of high-risk families may see a way to possibly alleviate their concerns, if the test is negative, or to render them more active with respect to preventive measures, if the test is positive. Although informed and aware of the risk of discrimination, they may consider it almost trivial in comparison with the suffering of breast or ovarian cancer.

On the contrary, other women perceive the risk of discrimination as too high, and its potential consequences as too disruptive for their lives, to be ignored. For them genetic biases would only compound already existing gender biases in employment, health care³¹and other aspects of life. Social biases with serious consequences have already appeared in the disguise of health concerns: unfortunate examples include sexual discrimination with respect to Hiv testing and racial discrimination with respect to sickle cell testing. Women's concerns are therefore justified in view of the past, and many patients already feel that not only they can vertically transmit the disease to their daughters, but they may also be vertically transmitting an increased risk of discrimination. Thus, some women feel forced to choose between knowledge as the power that they could acquire, and knowledge as the power that could be used against them by society. Clearly, this is a major unresolved issue, awaiting the active participation of all women in defense of their equal rights.

Does genetics affect our views on autonomy and trust?

Concern for one's children and family, as well as debate over rights, imply that we consider ourselves both as autonomous independent individuals and as relational individuals connected to one another. One of the main reasons for persons to request genetic testing is a concern for their offspring and relatives. Genetic testing for breast and ovarian cancers has been demonstrated to have a profound psychological impact on the entire family, including those members who do not carry a mutation.³²

Large debate in the ethical literature has surrounded issues of personal autonomy versus community goods. Occasionally, extreme positions have absolutized autonomy, but this scarcely reflects the reality of our existence, where from birth we are connected to one another. This connectedness at times conflicts with our desire to be completely autonomous and infringes on our personal rights. Recognition and respect for human rights founded on personal liberty is the foundation of our democratic societies, and medicine accordingly must place a particular emphasis on autonomy to protect patients' dignity and their right to self-determination. Emphasis on personal rights does not, however, change the relational essence of our being human, and genetics now, by increasingly revealing the links that unite mankind,³³comes as a reminder of our connectedness.³⁴There is, in fact, a rediscovered sense of belonging together, if only through our genes, which is one of the most positive and promising messages of genetics. The protagonists of today - the patients - say that when they enter the difficult path of genetic testing they are not alone nor do they wish to be so, and that their being a part of a community does not mean abdicating their autonomy, but merely redefining it.

This process of redefinition of autonomy involves also the rapport between patient and doctor, where relational aspects have always been essential. In the patient-doctor relationship genetics makes these aspects even more important as patients facing genetic testing rely on "trust". Trust is an essential ingredient in the patient-doctor relationship, an important ethical principle³⁵and the basis for certain modern ethical theories.³⁶Trust is increasingly important as one moves from the isolation of the autonomous moral agent (where the individual is alone) to the connectedness of a more relationally understood moral agency (where the individual is part of a society). In one realm responsibility arises out of contracts, most often among peers, and is limited to symmetrical relationships, where power is equally distributed.³⁷There the language is that of autonomy, self-determination and contractual obligations. In the other realm, responsibility often arises from asymmetrical relationships, where reciprocity exists in asymmetry.³⁸Here the language is that of vulnerability, dependability and caring. The patient-doctor relationship is at the same time a contractual relation based on mutual obligations and an asymmetrical relation based on the particular needs created by disease itself; thereby trust is an essential element of both.

As the responsibility of the scientific community with regard to issues in genetics is extremely high, the public needs and wishes to trust, for instance, that genetic knowledge will never be misused, whether for eugenic purposes (subtle eugenics can stem from increasing economical pressure in health care), or for more or less overt discrimination. In prenatal counseling, for instance, trust is especially needed for a woman who may have witnessed many of her relatives dying of breast and ovarian cancer, and may also feel pressured by a society with low acceptance of sickness. Trust is essential when facing decisions about prevention. An example would be the choice to perform a prophylactic mastectomy in a 25 year old woman carrying a Brca1 mutation: is surgery at that age less expensive than long-term measures, such as strict follow-up, or prevention trials or possible treatment for a later breast cancer? Women need to trust that their doctors will stand against economical pressure if necessary; and never make treatment decisions dictated by costs only. Whether it is the preliminary counseling about undergoing genetic testing, or subsequent personal and family counseling, or counseling about prevention and treatment options, trust is paramount for the person facing any decision-making based on genetic risk assessment. In this perspective, genetics itself is a potent reminder of how the connectedness of our moral agencies reflects also in the patient-doctor relationship and calls for a reappraisal of trust as an indispensable tool.

Does genetic knowledge increase control?

The fundamental philosophical issue in genetic testing - and genetics at large - is whether genetic knowledge expands or restricts the control that we have on our lives. Clearly, we are not our genome, and only in part is genetics helping us predicting our future; yet we seem to see genetic data as more fundamental and more inalterable than any other in the equation of life and to rely excessively on predictions based on genetic knowledge. Thus, for some women the knowledge of a very high-risk to develop breast cancer has a profound and limiting effect on their personal choices: the haunting specter of cancer appears as the final negation of freedom, and their life is determined by the expectation of a dire future. On the contrary, some women who have already been breast cancer patients feel that the quality of their life in terms of its intensity and depth has improved after they have confronted the disease, and they consider genetic risk as no different from any other risk in life - something to be dealt with and to possibly overcome. Finally, other women hold a more abstract belief that knowledge in itself always contributes to control and freedom.

Philosophers have long debated the meaning of freedom, and have either stressed the importance of free will or followed more deterministic views of causation of life events. The case of genetic testing does not differ philosophically from any other type of predestination. However, traditional philosophical thinking has been centered around principles that tend to underestimate relational aspects, especially in regard to what is perceived as controllable not only by 'me', but also by a common "us". The repercussions of testing positive for a genetic cancer predisposition, for instance, do not depend only on individual reactions, but also on society's attitudes towards disease, and on our collective perception of genetic abnormality. Control is thus more than a personal issue, since the normative standards for what can be controlled presuppose a shared understanding, which is in turn supported by various social practices. The concept of genetic predisposition to cancers or to other major diseases is indeed one in which scientific and philosophical understandings intersect, as statistical distributions and projections intersect with normative standards of acceptability, health and well-being. We will likely never find a common agreement as to whether genetic information increases or limits our control, for the answer involves our deepest personal selves. However, as a society, we can strive to create and share social practices that support a non-discriminatory approach to the advancement of human genetics.

Conclusive remarks

Major economical interests support the development of human genetics and interfere with the choices of both health-care providers and patients. Genetic testing is an area particularly exposed to the interference of economical interests, as even the professional motivation for offering such tests is often based on the monetary interests of physicians, laboratories and pharmaceutical industries. Thus the ethical implications of genetic testing can go unnoticed or can be clouded by an indiscriminate use founded on less than ethical reasons. Is genetics with its moral and social ramifications only an issue for the élite or can a deeper understanding of the philosophical and social implications of genetics really contribute to the progress of mankind? Genetics and its dilemmas are clearly exclusive of certain privileged societies and groups, while other major health concerns such as poverty, malnutrition, infant and childhood mortality, infectious disease epidemics and lack of basic medical support still remain the dominant reality in some parts of the West and in far too many other parts of the world. Yet the philosophical issues surrounding genetic testing may be generalizable, and the interest and the debate over genetics, far from clouding other important issues in science and in medicine, may stimulate a better understanding of the concept of diversity and foster a higher level of connectedness among all human beings. By so doing, the contribution of genetics to human progress may go beyond its limited medical aspects by deeply challenging our medical, moral and social engagement^.39Yet, thousand of years ago the Chorus in Antigone sang: 'Future things: not our domain. But in this today which unravels in front of us, what shall we do?'⁴⁰To this question genetics still provides no answers.

Acknowledgement: I am deeply indebted to Mrs. Kristine Salerno for her assistance in the preparation of this manuscript and to Dr. Hiroaki Mitsuya for his critical comments.

Notes

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Riassunto in Italiano

La recente scoperta di un test genetico, che permette di verificare una predisposizione ereditaria ai carcinomi mammari e ovarici, è di grande importanza scientifica e di eguale rilievo sul piano sociale ed etico. Molti dilemmi etici caratterizzano i tests genetici, ed assumono particolari sfumature in questo caso. Infatti, per la sua natura aggressiva e perché l'incidenza è in aumento, il carcinoma mammario è diventato un problema centrale nella salute delle donne. Le pazienti affette dal cancro al seno, e le donne in generale, sono spesso profondamente interessate a capirne l'eziopatologia e i possibili trattamenti, così come a discuterne le ramificazioni psicologiche, sociali e morali.

Questo articolo offre una riflessione sugli aspetti qualitativi del dibattito, così come sono emersi negli incontri con le pazienti prima della loro decisione finale di sottoporsi al test genetico. Benché i cinque temi ricorrenti nella pratica clinica non siano necessariamente rappresentativi di altre situazioni cliniche, essi illustrano alcuni fondamentali aspetti filosofici, etici e morali che sono al centro della nostra essenza umana e del nostro essere agenti morali, e che riflettono l'inestricabile connessione di medicina, cultura, normatività e filosofia di fronte alle questioni di genetica.

Nell'esposizione sono stati evitati i casi clinici particolari, per mantenere la confidenzialità, e non si è fatto uso di questionari, in quanto possono apparire riduttivi rispetto all'entità e complessità del problema.

La conclusione è che le sole risposte corrette ai dilemmi posti dai tests genetici per il carcinoma mammario sono quelle che nascono da una analisi insieme medica, sociale e filosofica.