Psycho-OncologyPsycho-Oncology 17: 733–736 (2008)Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/pon.1419

Editorial

Cancer genetic testing: current and emerging issues

Andrea Farkas Patenaude1,2� and Claire Julian-Reynier3,4

1Director of Psycho-Oncology Research, Dept. of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA2Associate Professor of Psychology, Dept. of Psychiatry, Harvard Medical School, Boston, MA3Inserm, U912, Marseille, France4Universite Aix-Marseille, UMR-S912, IRD, Institut Paoli-Calmettes, Marseille, France�Correspondence to: Department of Pediatric Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.

E-mail: andrea_patenaude@dfci.harvard.edu

This special issue on ‘Genetic Testing and Psycho-social Research’ is appearing a little more than adecade after the first studies on psychosocialaspects of cancer genetic testing were published inthe professional literature. The continuing excite-ment and the growing breadth and depth of thisnew field of study are reflected in the fact that thecall for papers for the current special issue yieldedmore submissions (from nine countries) than anyprevious Psycho-Oncology special issue. As medi-cine (and especially oncology) becomes increas-ingly intertwined with genetic advances, and as thenumber of people undergoing genetic testingincreases, it becomes all the more important thatwe understand the human factors influencinguptake of genetic tests, adherence to regimens ofscreening or surveillance recommended to muta-tion carriers and high-risk individuals, and issues ofindividual, family, and community impact ofgenetic technologies and genetic knowledge.Our special issue, like the field as a whole, has a

preponderance of articles focusing on hereditarybreast/ovarian cancer (HBOC). However, thepapers in this issue report on genetic testing impactfor a wide range of conditions from one of theearliest types of cancer genetic testing, p53 testingfor members of Li–Fraumeni Syndrome families,to the first report of genetic testing for familialmelanoma. Psychosocial aspects of both hereditarynon-polyposis colon cancer (HNPCC) and familialadenomatous polyposis (FAP) are reported. Somearticles focus on issues that have been of interestsince the beginning of studies in this field, such asmeasurement of distress and cancer worry for thoseapproaching and adapting to genetic testingdisclosure. Several focus on the complex issuesrelated to family communication of genetic infor-mation, evoking new dilemmas such as thetransmission of such information within familiesafter the tested family member had died. Othersdeal with emerging issues in counseling, such as theunderstanding of inconclusive test results showingan unclassified variant. Papers are also includedthat are related to optimizing the support of

patients with specific interventions, potential oractual, which may reduce the emotional burdens ofliving with hereditary cancer risk in a genetic age.

These papers reveal much of what we have learnedand are learning about how cancer genetic testingchanges the lives of those to whom it is provided.The strong hold of psychological factors on theactions of individuals in the face of scientificinformation provided through high-quality geneticcounseling and testing remains striking. Despitebeing told by medical professionals of the impor-tance of informing relatives about the presence of adeleterious familial cancer-predisposing mutation,it can take years before such information isconveyed by the tested individuals to some sisters,brothers, adult children, stepchildren, or parentsdue to psychological hesitancies that take prece-dence over motivations to altruistically inform[1,2]. Gender also impacts the use and dissemina-tion of genetic information. Koehly et al. [3]describe areas of overlap and non-continuity inthe knowledge and cancer anxiety felt by sisters.Ormondroyd et al. [2] studied dissemination ofBRCA1/2 results given to widows or other next ofkin of men with prostate cancer who died beforetheir results were available. The complexities ofconveying this information to at-risk relatives aredescribed in narratives from the subjects. The roleof women as ‘kin keepers’ has been previouslydescribed by Green et al. [4]. An issue for furtherinvestigation might be how these narratives andfamily dissemination patterns would be differenthad it been widowed husbands rather than wiveswho were provided with the BRCA1/2 test resultsand asked to inform relatives.

Some individuals testing negative for adenoma-tous polyposis coli mutations predisposing to FAPrefuse to be reassured by their negative result anddo not believe they are thereby freed from thefamily curse of early, increased predisposition tocolon cancer [5]. We have a convincing illustrationin the Vos et al. study [6] that contradictory ideasco-exist among women receiving results showing avariant of uncertain significance. In that study,

Copyright r 2008 John Wiley & Sons, Ltd.

many women with such results had two indepen-dent recollections, ‘a factual recollection of anuncertain result and a subjective interpretation thatimplies a genetic predisposition’. The latter affectedbehavior, as 10/19 who interpreted their result aspathogenic had had prophylactic surgery versus 0of 5 who felt this result was not informative.The question of what type and level of support

could reduce psychological burdens on patientsundergoing genetic counseling and testing ormaking subsequent decisions about screening orprophylactic surgery is informed by several papers.Wakefield et al. [7] found that women whosegenetic counseling was augmented by use of aBRCA1/2 decision aid felt more informed aboutgenetic testing, had clearer values, and had higherknowledge than control women. But, interestingly,providers expressed some resistance to using thedecision aid as a specific tool during the consulta-tion, leaving the authors to recommend flexibilityin the time of presentation and a need for work onthe psychology of provider delivery. The need fortargeted psychological services for the minority ofwomen who experience distress during theBRCA1/2 genetic counseling and testing processand after disclosure is discussed by Smith et al. [8]who report that most women in their study whohad undergone genetic counseling and testingwould not require such services. Shiloh et al. [9]stressed that educational intervention is not suffi-cient to help individuals with a combination ofpositive or uninformative mutation status andcertain personality characteristics who were moredistressed than average following genetic testing.They recommended tailoring cognitive–affectiveinterventions which speak to the particular psy-chological issues that preoccupy these individuals.In the Patenaude et al. study [10], the majority ofwomen who had undergone or were consideringprophylactic mastectomy felt that psychotherapeu-tic consultation would be of value in their decisionmaking and/or post-surgical adaption and hadstrong ideas about the preferred referral path andtherapist characteristics.We are aware that cultural differences affect how

people approach genetic assessment, but have littlespecific knowledge of non-Caucasian individuals’experience in coming for genetic counseling andtesting. The article by Lagos et al. [11] illustratesinteresting distinctions in fatalism as a culturallyrelevant concept with apparently different impacton Latina and African-American women consider-ing BRCA1/2 genetic testing. Mellon et al. [12]describe lower levels of risk perception for HBOCamong African-American women than Caucasianwomen in dyads of an affected woman and anunaffected, at-risk relative. Wakefield et al. [7]describe that they developed a paper-based deci-sion aid as opposed to computer-based USBRCA1/2 decision aids, as the paper version would

be more acceptable to their Australian cohort. Theimplication was that broad cultural differencesneed to be considered in the development ofservices and supports for patients within geneticmedicine clinics and that ‘one size’ does not workfor all.Comparison of the impact of psychosocial

factors across genetic testing for differing condi-tions and genes is more possible now that testingfor a wider range of conditions is occurring. It willhelp us to determine which are overriding psycho-social factors affecting subjects in all or mostgenetic testing circumstances and which are not.However, it is important to look at both con-siderations of similarities across disease groups anddifferences between studied samples to correctlyinterpret findings. Within this issue, Peterson et al.[13] show, for example, that family experienceswith the cancer diagnoses and deaths of first-degreerelatives and the personal cancer history of subjectsin Li–Fraumeni Syndrome families being preparedfor p53 testing show correlations with cancer-specific distress and perceived self-efficacy in deal-ing with test results. This is in contrast to thefinding by Smith et al. that personal cancer historyfor breast or ovarian cancer did not affectpsychological distress post-disclosure of BRCA1/2test results in their cohort. de Snoo et al. [14]discuss the challenge for individuals from high-riskmelanoma families of learning that they are also athigh risk for pancreatic cancer. This resonates withthe unanticipated information about increased riskfor ovarian cancer given to women from high-riskbreast cancer families undergoing genetic counsel-ing and testing for BRCA1/2 and for womenmutation carriers from HNPCC families who findthrough genetic counseling that they are also atincreased risk for endometrial and ovarian cancer.Comparison of similarity and difference in howsuch challenges are responded to will help to sortout the strength of factors such as gender or diseasegroup in evaluations of the impact of genetictesting and will help inform genetic counselingrecommendations for mutation carriers.Another factor of interest in the uptake of testing

is the clarity about the disease risks conveyed byhereditary mutations and the availability or lack ofavailability of recommended screening or surveil-lance for mutation carriers. The authors of the firstpublished psychosocial outcome study of genetictesting for melanoma [14] comment that the diseaserisks for their sample, a research cohort of p16-Leiden-positive families, were much clearer than islikely to be the case for many other groups at riskfor hereditary melanoma and they caution thatother groups may, therefore, experience loweruptake rates and more distress than that noted intheir study.Future studies will be better able to isolate

whether psychological, cultural, individual, family,

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DOI: 10.1002/pon

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socioeconomic, or medical factors are most promi-nent in predicting uptake and outcomes of cancergenetic testing. Which factors hold steady undervarying disease states and across geographic andcultural strata and which are highly variable? Howdoes access to testing under a variety of healthsystems affect psychosocial and medical outcomes?Also, an important factor in comparison of futurepsychosocial data about uptake and outcomes willbe to consider changes over time in screening andprevention guidelines. As efficacy data comeavailable that either support or refute previouslyexpert-opinion-supported recommendations tomutation carriers, physician behavior is likely tobe influenced, changing instructions and messagesto mutation carriers and at-risk individuals.Physician recommendation is a powerful motiva-tor, but, as these and other studies support, so, too,is family experience of cancer. How these areweighted and what screening or prevention adviceis accepted are important factors influencing thesuccess of genetic medicine.As the papers in this special issue illustrate, there

is a growing awareness of the family impact ofgenetic testing and of the complexity of theassociated issues in family communication. Thesepapers detail both the closeness of family mem-bers—in terms of shared views about risk perceptionand shared support and the problems in theexpectation that complex, important genetic infor-mation can be transmitted appropriately and in atimely manner to relatives with whom interpersonalcontact is of varying quality and frequency. Newmodels may be proposed in the future for sharingthe responsibility between genetics providers andfamily members for educating at-risk relatives. Suchmodels will require careful planning and ethicalconsideration to accommodate the challengingemotional links and divisions within families. Whilesome family members embrace the role of the‘informer’, others find it burdensome and over-whelming. Again, we may need to find mechanismsthat do not expect a ‘one size fits all’ approach tocomplex issues related to families affected byhereditary cancer predisposition.Some groups have received considerably more

attention to date in the psychosocial cancer genetictesting literature than others. Fewer men thanwomen, for example, have been studied in cancergenetic research, due to the early emphasis onBRCA1/2 genetic testing. Studies of conditions,such as HNPCC, which affect both men andwomen, will yield valuable information aboutgender differences in willingness to undergo coun-seling and testing and uptake of screening,surveillance, and prevention recommendations.Cultural minorities, too, have been little studied,but the voices of minority men and women will beimportant in rounding out the psychosocial dataon how genetic tests are integrated into medical

care for those with increased hereditary cancerpredisposition. Access not just to counseling andtesting but also to a lifetime of screening,surveillance, and prevention activities may reduceultimate medical costs, but will require on-goinginsurance coverage for these activities in order forthe ultimate goals of the genetic revolution to bereached. Issues of access will be better studied inthe decade to come. Concerns about privacy andconfidentiality of genetic information will have tobe addressed as well, as genetics becomes a moreintegrated part of clinical medicine.One issue related to family concerns, which will,

of necessity, grow over the next decade, is ourunderstanding of how a new generation of at-riskindividuals that comes of age knowing the muta-tion status of their parent makes decisions about itsfuture plans and health behaviors. As Clarke et al.in this issue described, there can be considerabledecisional conflict about how and when to sharefamily genetic information. Once shared, however,informed young adults will make genetic testing,reproductive, marital, career, and health decisionsagainst the background of knowledge of theirhereditary cancer risk. Data about how cancerpredisposition influences these young people’s well-being and their choices will inform future genera-tions growing up with the expectation of having, ifthey desire, considerable information about theirhereditary disease risks.Support services are being designed and planned

to help in the transmission of genetic knowledge,the integration of personal values into decisionmaking about testing and screening, and thedissemination of genetic information throughfamilies. Future research will examine the valueof decision aids, support groups, both in-personand on-line, and individual targeted psychologicaltreatments in reducing the guilt, worry, confusion,and stress, which can come with knowledge offamily cancer predisposition, genetic testing, andsubsequent health decisions.For the future, it is clear that we need comple-

mentary qualitative and quantitative methods inorder to understand more comprehensively thepsychosocial issues at stake in the transfer ofcancer genetic knowledge to clinical practice. Smallsample sizes remain a major limitation whenstatistical comparison is involved. Selected sam-ples, not representative of the target population,impair the generalizability of findings from manypsychosocial studies in cancer genetics.While some measures adapted specifically to

genetic testing, such as the Impact of Event Scale[15] or the Cancer Worry Scale [16], are broadlyused, there remains a certain amount of hetero-geneity among the psychological measures used indifferent studies of genetic testing outcomes. Thereis also a lack of agreement about exactly whichfollow-up time points are critical to study. It would

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be ideal if it were possible to develop large nationalor even international cohorts that could be studiedwith common protocols over long periods of time sothat more robust predictions could be made aboutthe medical, psychological, and social consequencesof genetic testing for a range of disorders in peopleof different ages, cultures, and family experienceswith cancer. Given that the Human Genome Projectitself was able to achieve transparency in the sharingof data, we might hope that a similar frame could bedeveloped for behavioral study of the cominglegions of individuals who will undergo genetictesting for a wide range of diseases. In the years tocome it will be relevant, for example, to developinternational approaches to assess the impact ofdirect marketing of genetic testing by privatecompanies, not only assessing uptake rates, but alsothe medical and psychosocial consequences of thisapproach to genetic assessment.It is crucial that this field of psychosocial aspects

of cancer genetic testing should continue to growand prosper in particular to understand how thecomplex new developments in genetic knowledgeand testing affect patients and their family mem-bers. The coming decade of research will see anexplosion of genetic testing for a wider range ofconditions and genes, further integration of genet-ics and clinical practice, and, hopefully, a fuller,more refined understanding of how human factorsaffect this integration. The studies reported in thisspecial issue reflect many of the interest areas inwhich this future progress will occur, while alsoillustrating some of the accomplishments of thepast decade or so of research in psychosocialcancer genetics.

References

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2. Ormondroyd E, Moynihan C, Ardern-Jones A et al.Communicating genetics research results to families:problems arising when the patient participant isdeceased. Psycho-Oncology 2008;17:804–811.

3. Koehly L, Peters J, Kuhn N et al. Sisters in hereditarybreast and ovarian cancer families: communal coping,social integration and psychological well-being. Psycho-Oncology 2008;17:812–821

4. Green J, Richards M, Murton F, Stratham H, HallowellN. Family communication and genetic counseling: thecase of hereditary breast and ovarian cancer. J GenetCouns 1997;6:45–60.

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10. Patenaude AF, Orozco S, Li X et al. Support needs andacceptability of psychological and peer consultation:attitudes of 108 women who had undergone or wereconsidering prophylactic mastectomy. Psycho-Oncology2008;17:831–843.

11. Lagos VI, Perez MA, Ricker CN et al. Social–cognitiveaspects of underserved Latinas preparing to undergogenetic cancer risk assessment for hereditary breast andovarian cancer. Psycho-Oncology 2008;17:774–782.

12. Mellon S, Gold R, Janisse J et al. Risk perception andcancer worries in families at increased risk of familialbreast/ovarian cancer. Psycho-Oncology 2008;17:756–766.

13. Peterson SK, Pentz RD, Marani SK et al. Psychologicalfunctioning in persons considering genetic counselingand testing for Li–Fraumeni Syndrome. Psycho-Oncol-ogy 2008;17:783–789

14. de Snoo F, Riedjik S, van Mil A et al. Genetic testing infamilial melanoma: uptake and implications. Psycho-Oncology 2008;17:790–796.

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Psycho-Oncology 17: 733–736 (2008)

DOI: 10.1002/pon