Journal of Genetic Counseling, Vol. 8, No. 5, 1999
Genetic Testing Considerations in Breast Cancer Patients Liz France,1 JonathonGray,1 6 Glyn Elwyn,2 Mark Tischkowitz,1 Kate Brain,1 Julian Sampson,1 Cathy Anglim,1 Angus Clarke,1 Evelyn Parsons,5 Helen Sweetland,3 Robert Mansel,3 Peter Barrett-Lee,4 Peter Harper1
Genetic testing is now feasible for a growing number of cancers. Although the implications for unaffected relatives have been widely described, the impact of the tests on affected individuals are often not recognized. We present and discuss four cases that highlight some of the issues—for example, feelings of guilt and anxiety, intrafamilial conflict, and support needs—that may arise in testing affected individuals. We offer some suggestions to aid in the approach to such testing. KEY WORDS: Affected; genetic testing; counseling.
INTRODUCTION Breast cancer is a multifactorial condition which affects approximately 1 in 12 women in the UK. Family history is widely recognized as a powerful predictor of breast cancer, and an inherited predisposition is thought to account for approximately 5% of all cases (Claus et al., 1991). BRCA 1 mutations account for approximately 45% of families with familial breast cancer alone, and for most of those families with breast and ovarian cancer (Easton et al., 1993). Germline mutations of BRCA 2 are predicted to account for 35% of families with multiple cases of breast cancer, as well as being associated 1The Institute of Medical Genetics, University of Wales Healthcare NHS Trust, Cardiff. of Postgraduate Studies and Department of General Practice, University of Wales College of Medicine, Cardiff. 3Department of Surgery, University of Wales College of Medicine, Cardiff. 4Velindre NHS Trust, Whitchurch Road, Cardiff. 5 Department of Nursing Studies, University of Wales College of Medicine, Cardiff. 6Correspondence should be directed to Dr. Jonathon Gray, Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, CF44XN; e-mail: [email protected]. 2 School
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with an increased risk of male breast cancer, ovarian cancer, and prostate and pancreatic cancer (Gayther et al., 1997). These developments in molecular genetics, together with increased media awareness, have resulted in an increased demand for genetic counseling and testing by individuals with a family history of breast cancer. Genetic testing to predict whether an individual has inherited a breast cancer susceptibility gene is usually dependent on availability of a living affected relative. The aim is to identify the "family" mutation in that affected individual before proceeding to test the "worried well" in the family. Therefore, genetic (DNA) testing depends on the availability of a blood sample from a living relative in whom breast cancer has been diagnosed. The genetic testing of women already known to have breast cancer is normally visualized by the medical profession as posing fewer issues than the testing of unaffected women at risk. However, our experience suggests that this is not necessarily the case. The cases presented arose from research projects evaluating cancer genetics provision in Wales. We believe they could equally have been chosen from the various cancer genetic "services" already in place around the UK. CASE HISTORY 1 Mrs. D. aged 28 (Fig. 1) was given an estimated 30% residual lifetime risk of developing breast cancer and, following a reflective period, contacted the genetic nurse specialist (GNS) to request a counseling appointment to discuss further genetic assessment. Mrs. D. was accompanied by her mother Mrs. L., aged 58, who had a history of bilateral breast cancer. Mrs. L.'s right breast cancer was diagnosed at age 44, and she underwent a right mastectomy. Subsequently she developed left breast cancer at age 50 and underwent a left radical mastectomy. Mrs. L. reported that she had been well since and was monitored annually by her consultant breast surgeon. Mrs. D. asked that her mother be present at her genetic counseling appointment because her mother had strongly intimated that she would be willing to give a blood sample "to help my daughter because I don't want her to go through what I've been through." Although we try to accommodate our clients' wishes, we were concerned that problems could occur, that is, feeling of coercion or sense of duty to give a DNA sample if both Mrs. D. and Mrs. L. received pretest information together. When the medical implications of BRCA1/2 gene testing were discussed, Mrs. L. became distressed. She explained that a close friend, who'd also had breast cancer 10 years ago, had recently been diagnosed with ovarian cancer. The fact that the geneticist had advised Mrs. L. that there was an increased risk of developing ovarian cancer in BRCA1/2 carriers immediately raised fears and doubts about her decision to give a blood sample for a BRCA1/2 mutation
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Fig. 1, D = male; O = female; • = female affected with breast cancer.
search: "He confirmed my worst fear, I don't know if I can cope with that information [risk of ovarian cancer] if I carry the gene." When Mrs. L. was contacted by the GNS a week later, after an opportunity to talk with her husband and daughter, she had decided not to have any further genetic testing. This case history illustrates the importance of pre- and posttest counseling for the affected individual and the provision of ongoing support by appropriately qualified professionals. The process of mutation testing cannot be considered in isolation: "This new knowledge and the ways in which it is employed may have profound consequences for family life and relationships" (Richards, 1996). In this case history it is apparent that Mrs. L. was keen at first to have the test, but after she had understood the implications and discussed her concerns with both her husband and her daughter, she decided against mutation analysis. We suggest that in some families, there is the potential for coercion or for agreement to testing out of a sense of familial duty. Wherever possible, we would recommend that the "affected" individual have personal pretest counseling to eliminate the possibility of extraneous familial influences in the decision-making process.
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CASE HISTORY 2 Mrs. P. aged 29 (Fig. 2) was given an estimated 42% residual lifetime risk of developing breast cancer. Having obtained consent, the GNS counseled the affected relative at home before taking a sample for BRCA1/2 mutation analysis. When the positive BRCA1 result was conveyed to the client at home by the experienced GNS, she became very distressed, particularly regarding her increased risk of ovarian and other cancers. In any genetic condition there is the potential for psychological morbidity as a result of the testing process, which may take the form of guilt, excessive anxiety, and depression: "I know you explained everything and discussed the issues and consequences with me, but now I know that I definitely have the gene, I am really worried about having another cancer." Case History 2 highlights the need for ongoing support and, most important, posttest support and counseling for "affected" individuals. In testing for a cancer predisposition, we are providing information regarding an increased risk of developing a further cancer.
Fig. 2. D = male; O = female; • = female affected with breast cancer.
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Fig. 3. D = male; O = female; • = female affected with breast cancer.
CASE HISTORY 3 Mrs. A. aged 46 (Fig. 3), was given a 26% estimated residual high lifetime risk of developing breast cancer. Following an initial genetic counseling appointment, Mrs. A. stated that she wished to proceed with testing, and she was asked to forward the appropriate consent forms to her sister, Mrs. V., her only living "affected" relative. After following the accepted consenting procedures, Mrs. V. was visited at home by the GNS. Mrs. V. aged 58, had been diagnosed 3 months previously with Grade 2 invasive breast carcinoma. During the pretest counseling, it became apparent that Mrs. V. had been estranged from her sister for a number of years and contact had been re-established by Mrs. A. only very recently, following her clinic appointment, when the possibility of DNA testing had first been raised. Several issues arose in the counseling session. Mrs. V.'s husband expressed feelings of hostility toward Mrs. A. because of the way she had treated his wife in the past, and second, he felt his wife was being "used" and was not supportive of his wife giving a blood
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sample. Mrs. V. expressed ambivalent feelings. On the one hand, she felt morally obliged to help her sister, but on the other, she did not want to go against her husband's wishes because he had been very supportive during her illness and was her only emotional support. Mrs. V. was fragile and vulnerable and welcomed the opportunity to explore her feelings in a safe, nonjudgmental counseling interaction. The third case history illustrates that genetics involves complex issues of kinships within families (Richards, 1996). Communication patterns within family groupings are diverse and invariably raise dynamic concerns. Obtaining pedigree information during a genetic counseling process can provide an insight into the ways the family network functions. Family members often lose contact, and in some instances, this may only be reinstated when a history of a potentially inherited condition is investigated. Renewed family contact after years of silence, acrimonious or otherwise, may influence the decision-making process. Entering this process requires both expertise and sensitivity. In this respect, the guiding principles of autonomy and privacy are paramount and must be respected. Autonomy is the individual's capacity for self-determination and privacy, which relate to the individual's right to maintain control of personal information (Wood-Harper and Harris, 1996). CASE HISTORY 4 Mrs. B. (Fig. 4), aged 35, was given an estimated 26% residual lifetime risk of developing breast cancer. Following an initial consultation, she obtained consent for us to review the notes of her affected relative (aunt) living in northern England. After she had been counseled regarding genetic testing by the GNS, the aunt agreed to see her general practitioner to ask if he would undertake the blood sampling for DNA testing. Anticipating that this was likely to be a new task, background information about the test and its indication was sent to the general practitioner (GP). The correspondence stated that the patient could be referred to a local genetics department, and that we would be prepared to provide any further details by telephone. Several days later, the nurse specialist received a telephone call form the GP to the effect that he was far too busy to take blood and that the request should have been made directly to his practice nurse. Case 4 raises many questions for various specialities, but in particular for primary care. The new developments in genetics are here already and inevitably will bring with them increasing work for the primary health care team. The impact of genetic testing on primary-care services is likely to be enormous, in terms of demand both for information about the recently available tests and for advice after a result is known. Many general practitioners are increasingly wary about taking on new tasks (GMSC, 1996) and may well regard "genetic testing" as a process warranting referral to specialist services. It is also unlikely that many people will pay for genetic counseling to satisfy such a demand. What then? More guidelines,
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Fig. 4. D = male; O = female; • = female affected with breast cancer.
telephone advice lines, web sites, more continuing education? All these may help, but they do not tackle the fundamental problems of time and the willingness to add this task to the other portfolio of work falling on primary-care physicians. In Case 4, our information to the general practitioner clearly did not help, and the blood taking devolved to the practice nurse. If the patient was looking for a further discussion of the issues, then we did not facilitate this adequately. These cases highlight the importance of pre- and posttest counseling and the provision of ongoing support by appropriately qualified health care professionals. Ensuring the availability of professional support for "affected" women at a distance from the initiating genetic center is also identified as an important issue for discussion. The medical and psychosocial implications of DNA testing for inherited cancers in affected individuals can be complex and are sometimes not appreciated by professionals or the public. Genetic counseling requires a range of experience and specialist training to appreciate the often complex interplay between the clinical scenarios and the ethical dilemmas seen in genetics.
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The influx of other health professionals bringing their views and experience into this area is to be welcomed. However the appropriate time and resources must be made available for the necessary additional training in genetics. There needs to be debate at all levels as to how best our developing cancer genetic services can share information with colleagues in primary care, in ways that minimize their ever-increasing workloads. DISCUSSION The majority of literature about the psychosocial implications of BRCA1/2 mutation testing has focused on the high-risk worried-well women. There is a dearth of literature relating to the psychosocial implications for the affected individual undergoing mutation testing. From our analysis of these case histories, as discussed above, we suggest there are similar psychosocial and emotional implications for the affected family member undergoing mutation testing and for the at-risk well individual in the family (Lerman, 1997; Baum et al.,1997; Croyle et al., 1997). In addition to the shared psychosocial issues, there are reactions and specific implications for the affected individual—for example, the feeling of coercion and a sense of duty—which merit additional consideration when offering pretest counselling. Another unique difference for affected individuals is their previous cancer diagnosis and the fact that they will have experienced the emotional and psychological reaction associated with that diagnosis. Fallowfield and Clark (1991) reported categories of response to a breast cancer diagnosis, namely, denial, fighting spirit, stoic acceptance, anxious/depressed acceptance, and helpless/hopeless. In the pretest counseling process, there is the potential for all these emotions to surface when the medical implications for BRCA1/2 carriers are discussed. The emotional reaction to mutation testing may be dependent on the length of time that has elapsed since the breast cancer diagnosis because confidence, adaptation, and adjustment usually increase over time (Fallowfield and Clark, 1991). However, there is very little research evidence about the levels of emotional distress experienced when women discover a recurrence of cancer. For some, it may end the uncertainty because they had always believed that it would return (Fallowfield and Clark, 1991). This contrasts with evidence that a recurrence provokes more emotional distress than the original diagnosis (Holland, 1977). However, Lloyd (1979) and Rosch (1981) suggest that cancer patients are chronically stressed by the constant threat of recurrence. A study by Croyle et al. (1997) on the psychological responses to BRCA1 mutation testing concluded that the experience of a cancer diagnosis lessens the psychological distress in mutation carriers. This may be because these women experienced greater cancer-related distress at diagnosis, and therefore mutation testing in that context may moderate the psychological reaction. However, the authors suggest that these data may underestimate the distress
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experienced by individuals undergoing mutation testing where comprehensive preand posttest counseling is not available. In view of the lack of definitive data about range of psychological reactions and impact of mutation testing for the affected relative, it is important to offer comprehensive pretest counseling. A further consideration in offering presymptomatic testing to affected individuals in a family is the maintenance of a healthy concept of self. Many cancer patients who have developed a sporadic cancer are able to separate their self from the disease in that they are a person who has cancer, whereas individuals who have inherited a BRCA1/2 susceptibility gene may perceive themselves as cancer patients due to their predetermined genotype (Croyle et al., 1997). Finally Case Histories 1 and 3 identify the potential for "coercion" and "a sense of duty." Dudok de Wit et al. (1997) highlight the difficulties of disseminating information about mutation analysis and the involvement of affected individuals for predictive testing. In their case history, they report that the affected individual felt like a "guinea pig," that the professionals were not interested in her as a person, and that their concern was only for the predictive value of her DNA. A similar situation is reflected in Case History 3, where there is risk of coercion from the at-risk sister and a perceived sense of filial duty to undertake mutation testing which may override the concerns and implications for her affected sister. In effect, affected individuals may be induced to feel it is their duty to help the at-risk individual at the expense of their psychological and emotional coping strategies. These ethical issues of autonomy, justice, and nonmaleficence are important considerations not only for informed consent, but for the ethos of genetic counseling. In conclusion, the case histories highlight the similarities and differences in implications for the at-risk individual and the affected relative. These complex issues merit the provision of comprehensive pre- and posttest counseling and support, for both patient groups. From our own experiences so far, we can make some suggestions: • Affected family members should be seen by the local genetic service. If outside the area served by the initiating genetics unit, then arrangements should be made with that individual's local genetic service for the collection of samples, counseling, and support. Some genetic centers throughout the UK have developed an agreed liaison policy and reciprocal arrangements for the collection of blood samples and genetic counseling support services. If such a local genetic service is not possible, then the affected individual should be encouraged to nominate a professional support person, perhaps the oncologist or GP. Such person should then be supplied with educational and support backup from the initiating genetic service. Wherever possible, a referral to a clinical genetics service is preferable to try to maintain a "family"-based approach, coordinating the care of the affected individuals and their family members.
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• Affected individuals should be contacted only via the at-risk family member so that no unexpected contact is made by health professionals. The individual requesting testing should coordinate most communications within the family, for example, requesting consent to release clinical notes. "Highrisk" individuals who have an appropriate family structure and, following presymptomatic testing counseling, wish to proceed with DNA testing are asked to contact a living affected relative to obtain her permission to be contacted. Once this permission has been received, the genetic nurse specialist contacts the affected individual to obtain written informed consent, and to obtain a blood sample for BRCA1/2 DNA mutation analysis. • Counseling and information for the affected family member should cover the many medical, ethical, psychosocial, and practical areas (Chadwick and Ngwena, 1992). • Adequate follow-up for the affected family member should be confirmed to be in place, perhaps with an agreed-on health professional coordinating the screening and management. CONCLUSIONS We suggest that testing a family member with cancer for predisposing genes requires careful consideration. Where possible individual counseling and information should be given. Sometimes long-term follow-up is necessary. We are concerned that in the rush to offer testing to women at risk, the concerns of the affected family member, who must be tested first (in most protocols), may be lost because of a lack of service resources or the enthusiasm for research. ACKNOWLEDGMENTS L. France funded by ICRF, J. Gray funded by NHS(Wales) R&D, and now Tenovus the Cancer Charity, K. Brain and C. Anglim funded by MRC.
REFERENCES Baum A, Friedman AL, Zakowski SG (1997) Stress and genetic testing for disease risk. Health Psychol 16:8-19. Chadwick R, Ngwena C (1992) The development of a normative standard in counseling for genetic disease: Ethics and law. J Soc Welf Family Law 276—295. Claus EB, Risch NJ, Thompson WD (1991) Genetic analysis of breast cancer in the cancer and steroid hormone study. Am J Hum Genet 48:232-242. Croyle RT, Achilles JS, Lerman C (1997a) Psychologic aspects of cancer genetic testing. Cancer Supplement 80(3):569-575. Croyle RT, Smith KR, Botkin JR, Baty B, Nash J (1997b) Psychological responses to BRCA1 mutation testing: preliminary findings. Health Psychol 16:163-172.
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Dudok de Wit AC (1997) BRCA1 in the family: A case description of the psychological implications. Am J Med Genet 71:63-71. Easton DF, Bishop DT, Ford D, Crockford GP (1993) Genetic linkage analysis in familial breast and ovarian cancer results from 214 families. Am J Hum Genet 52:678-701. Fallowfield L, Clark A (1991) Breast Cancer. Great Britain: Routledge. Gayther SA, Mangion J, Russel P, Stal S, Barfoot R, Ponder BAJ, Stratton M, Easton D (1997) Variation of risks of breast and ovarian cancer associated with different germline mutations of BRCA2 gene. Nat Genetics 15:103-105. General Medical Services Committee of the BMA (1996) Core Services: Taking the Initiative. London: GMSC. Holland JC (1977) Psychological aspects of oncology. Med Clin N Am 61:737-748. Lerman C (1997a) Psychological aspects of genetic testing for cancer susceptibility. In Krantz D (ed) Perspectives in Behavioural Medicine. Hillsdale, NJ: Erilbaum. Lerman C (1997b) Psychological aspects of genetic testing: Introduction to the Special Issue. Health Psychol 16(l):3-7. Lloyd G (1979) Psychological stress and coping: mechanisms in patients with cancer. In: Stoll BA (ed) Mind and Cancer Prognosis. New York: Wiley. Richards M (1996) Families, kinship and genetics. In: Marteau T, Richards M (eds) The Troubled Helix: Social and Psychological Implications of the New Human Genetics. Cambridge: Cambridge University Press, pp 249-274. Rosch P (1981) Stress: Cause or Cure of Cancer? In: Psychotherapeutic Treatment of Cancer Patients. New York: Free Press. Wood-Harper J, Harris J (1996) Ethics of human genome analysis: Some virtues and vices In: Marteau T, Richards M (eds) The Troubled Helix: Social and Psychological Implications of the New Human Genetics. Cambridge: Cambridge University Press, pp 274—294.
Genetic Testing Considerations in Breast Cancer Patients Liz France,1 JonathonGray,1 6 Glyn Elwyn,2 Mark Tischkowitz,1 Kate Brain,1 Julian Sampson,1 Cathy Anglim,1 Angus Clarke,1 Evelyn Parsons,5 Helen Sweetland,3 Robert Mansel,3 Peter Barrett-Lee,4 Peter Harper1
Genetic testing is now feasible for a growing number of cancers. Although the implications for unaffected relatives have been widely described, the impact of the tests on affected individuals are often not recognized. We present and discuss four cases that highlight some of the issues—for example, feelings of guilt and anxiety, intrafamilial conflict, and support needs—that may arise in testing affected individuals. We offer some suggestions to aid in the approach to such testing. KEY WORDS: Affected; genetic testing; counseling.
INTRODUCTION Breast cancer is a multifactorial condition which affects approximately 1 in 12 women in the UK. Family history is widely recognized as a powerful predictor of breast cancer, and an inherited predisposition is thought to account for approximately 5% of all cases (Claus et al., 1991). BRCA 1 mutations account for approximately 45% of families with familial breast cancer alone, and for most of those families with breast and ovarian cancer (Easton et al., 1993). Germline mutations of BRCA 2 are predicted to account for 35% of families with multiple cases of breast cancer, as well as being associated 1The Institute of Medical Genetics, University of Wales Healthcare NHS Trust, Cardiff. of Postgraduate Studies and Department of General Practice, University of Wales College of Medicine, Cardiff. 3Department of Surgery, University of Wales College of Medicine, Cardiff. 4Velindre NHS Trust, Whitchurch Road, Cardiff. 5 Department of Nursing Studies, University of Wales College of Medicine, Cardiff. 6Correspondence should be directed to Dr. Jonathon Gray, Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, CF44XN; e-mail: [email protected]. 2 School
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with an increased risk of male breast cancer, ovarian cancer, and prostate and pancreatic cancer (Gayther et al., 1997). These developments in molecular genetics, together with increased media awareness, have resulted in an increased demand for genetic counseling and testing by individuals with a family history of breast cancer. Genetic testing to predict whether an individual has inherited a breast cancer susceptibility gene is usually dependent on availability of a living affected relative. The aim is to identify the "family" mutation in that affected individual before proceeding to test the "worried well" in the family. Therefore, genetic (DNA) testing depends on the availability of a blood sample from a living relative in whom breast cancer has been diagnosed. The genetic testing of women already known to have breast cancer is normally visualized by the medical profession as posing fewer issues than the testing of unaffected women at risk. However, our experience suggests that this is not necessarily the case. The cases presented arose from research projects evaluating cancer genetics provision in Wales. We believe they could equally have been chosen from the various cancer genetic "services" already in place around the UK. CASE HISTORY 1 Mrs. D. aged 28 (Fig. 1) was given an estimated 30% residual lifetime risk of developing breast cancer and, following a reflective period, contacted the genetic nurse specialist (GNS) to request a counseling appointment to discuss further genetic assessment. Mrs. D. was accompanied by her mother Mrs. L., aged 58, who had a history of bilateral breast cancer. Mrs. L.'s right breast cancer was diagnosed at age 44, and she underwent a right mastectomy. Subsequently she developed left breast cancer at age 50 and underwent a left radical mastectomy. Mrs. L. reported that she had been well since and was monitored annually by her consultant breast surgeon. Mrs. D. asked that her mother be present at her genetic counseling appointment because her mother had strongly intimated that she would be willing to give a blood sample "to help my daughter because I don't want her to go through what I've been through." Although we try to accommodate our clients' wishes, we were concerned that problems could occur, that is, feeling of coercion or sense of duty to give a DNA sample if both Mrs. D. and Mrs. L. received pretest information together. When the medical implications of BRCA1/2 gene testing were discussed, Mrs. L. became distressed. She explained that a close friend, who'd also had breast cancer 10 years ago, had recently been diagnosed with ovarian cancer. The fact that the geneticist had advised Mrs. L. that there was an increased risk of developing ovarian cancer in BRCA1/2 carriers immediately raised fears and doubts about her decision to give a blood sample for a BRCA1/2 mutation
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Fig. 1, D = male; O = female; • = female affected with breast cancer.
search: "He confirmed my worst fear, I don't know if I can cope with that information [risk of ovarian cancer] if I carry the gene." When Mrs. L. was contacted by the GNS a week later, after an opportunity to talk with her husband and daughter, she had decided not to have any further genetic testing. This case history illustrates the importance of pre- and posttest counseling for the affected individual and the provision of ongoing support by appropriately qualified professionals. The process of mutation testing cannot be considered in isolation: "This new knowledge and the ways in which it is employed may have profound consequences for family life and relationships" (Richards, 1996). In this case history it is apparent that Mrs. L. was keen at first to have the test, but after she had understood the implications and discussed her concerns with both her husband and her daughter, she decided against mutation analysis. We suggest that in some families, there is the potential for coercion or for agreement to testing out of a sense of familial duty. Wherever possible, we would recommend that the "affected" individual have personal pretest counseling to eliminate the possibility of extraneous familial influences in the decision-making process.
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CASE HISTORY 2 Mrs. P. aged 29 (Fig. 2) was given an estimated 42% residual lifetime risk of developing breast cancer. Having obtained consent, the GNS counseled the affected relative at home before taking a sample for BRCA1/2 mutation analysis. When the positive BRCA1 result was conveyed to the client at home by the experienced GNS, she became very distressed, particularly regarding her increased risk of ovarian and other cancers. In any genetic condition there is the potential for psychological morbidity as a result of the testing process, which may take the form of guilt, excessive anxiety, and depression: "I know you explained everything and discussed the issues and consequences with me, but now I know that I definitely have the gene, I am really worried about having another cancer." Case History 2 highlights the need for ongoing support and, most important, posttest support and counseling for "affected" individuals. In testing for a cancer predisposition, we are providing information regarding an increased risk of developing a further cancer.
Fig. 2. D = male; O = female; • = female affected with breast cancer.
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Fig. 3. D = male; O = female; • = female affected with breast cancer.
CASE HISTORY 3 Mrs. A. aged 46 (Fig. 3), was given a 26% estimated residual high lifetime risk of developing breast cancer. Following an initial genetic counseling appointment, Mrs. A. stated that she wished to proceed with testing, and she was asked to forward the appropriate consent forms to her sister, Mrs. V., her only living "affected" relative. After following the accepted consenting procedures, Mrs. V. was visited at home by the GNS. Mrs. V. aged 58, had been diagnosed 3 months previously with Grade 2 invasive breast carcinoma. During the pretest counseling, it became apparent that Mrs. V. had been estranged from her sister for a number of years and contact had been re-established by Mrs. A. only very recently, following her clinic appointment, when the possibility of DNA testing had first been raised. Several issues arose in the counseling session. Mrs. V.'s husband expressed feelings of hostility toward Mrs. A. because of the way she had treated his wife in the past, and second, he felt his wife was being "used" and was not supportive of his wife giving a blood
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sample. Mrs. V. expressed ambivalent feelings. On the one hand, she felt morally obliged to help her sister, but on the other, she did not want to go against her husband's wishes because he had been very supportive during her illness and was her only emotional support. Mrs. V. was fragile and vulnerable and welcomed the opportunity to explore her feelings in a safe, nonjudgmental counseling interaction. The third case history illustrates that genetics involves complex issues of kinships within families (Richards, 1996). Communication patterns within family groupings are diverse and invariably raise dynamic concerns. Obtaining pedigree information during a genetic counseling process can provide an insight into the ways the family network functions. Family members often lose contact, and in some instances, this may only be reinstated when a history of a potentially inherited condition is investigated. Renewed family contact after years of silence, acrimonious or otherwise, may influence the decision-making process. Entering this process requires both expertise and sensitivity. In this respect, the guiding principles of autonomy and privacy are paramount and must be respected. Autonomy is the individual's capacity for self-determination and privacy, which relate to the individual's right to maintain control of personal information (Wood-Harper and Harris, 1996). CASE HISTORY 4 Mrs. B. (Fig. 4), aged 35, was given an estimated 26% residual lifetime risk of developing breast cancer. Following an initial consultation, she obtained consent for us to review the notes of her affected relative (aunt) living in northern England. After she had been counseled regarding genetic testing by the GNS, the aunt agreed to see her general practitioner to ask if he would undertake the blood sampling for DNA testing. Anticipating that this was likely to be a new task, background information about the test and its indication was sent to the general practitioner (GP). The correspondence stated that the patient could be referred to a local genetics department, and that we would be prepared to provide any further details by telephone. Several days later, the nurse specialist received a telephone call form the GP to the effect that he was far too busy to take blood and that the request should have been made directly to his practice nurse. Case 4 raises many questions for various specialities, but in particular for primary care. The new developments in genetics are here already and inevitably will bring with them increasing work for the primary health care team. The impact of genetic testing on primary-care services is likely to be enormous, in terms of demand both for information about the recently available tests and for advice after a result is known. Many general practitioners are increasingly wary about taking on new tasks (GMSC, 1996) and may well regard "genetic testing" as a process warranting referral to specialist services. It is also unlikely that many people will pay for genetic counseling to satisfy such a demand. What then? More guidelines,
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Fig. 4. D = male; O = female; • = female affected with breast cancer.
telephone advice lines, web sites, more continuing education? All these may help, but they do not tackle the fundamental problems of time and the willingness to add this task to the other portfolio of work falling on primary-care physicians. In Case 4, our information to the general practitioner clearly did not help, and the blood taking devolved to the practice nurse. If the patient was looking for a further discussion of the issues, then we did not facilitate this adequately. These cases highlight the importance of pre- and posttest counseling and the provision of ongoing support by appropriately qualified health care professionals. Ensuring the availability of professional support for "affected" women at a distance from the initiating genetic center is also identified as an important issue for discussion. The medical and psychosocial implications of DNA testing for inherited cancers in affected individuals can be complex and are sometimes not appreciated by professionals or the public. Genetic counseling requires a range of experience and specialist training to appreciate the often complex interplay between the clinical scenarios and the ethical dilemmas seen in genetics.
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The influx of other health professionals bringing their views and experience into this area is to be welcomed. However the appropriate time and resources must be made available for the necessary additional training in genetics. There needs to be debate at all levels as to how best our developing cancer genetic services can share information with colleagues in primary care, in ways that minimize their ever-increasing workloads. DISCUSSION The majority of literature about the psychosocial implications of BRCA1/2 mutation testing has focused on the high-risk worried-well women. There is a dearth of literature relating to the psychosocial implications for the affected individual undergoing mutation testing. From our analysis of these case histories, as discussed above, we suggest there are similar psychosocial and emotional implications for the affected family member undergoing mutation testing and for the at-risk well individual in the family (Lerman, 1997; Baum et al.,1997; Croyle et al., 1997). In addition to the shared psychosocial issues, there are reactions and specific implications for the affected individual—for example, the feeling of coercion and a sense of duty—which merit additional consideration when offering pretest counselling. Another unique difference for affected individuals is their previous cancer diagnosis and the fact that they will have experienced the emotional and psychological reaction associated with that diagnosis. Fallowfield and Clark (1991) reported categories of response to a breast cancer diagnosis, namely, denial, fighting spirit, stoic acceptance, anxious/depressed acceptance, and helpless/hopeless. In the pretest counseling process, there is the potential for all these emotions to surface when the medical implications for BRCA1/2 carriers are discussed. The emotional reaction to mutation testing may be dependent on the length of time that has elapsed since the breast cancer diagnosis because confidence, adaptation, and adjustment usually increase over time (Fallowfield and Clark, 1991). However, there is very little research evidence about the levels of emotional distress experienced when women discover a recurrence of cancer. For some, it may end the uncertainty because they had always believed that it would return (Fallowfield and Clark, 1991). This contrasts with evidence that a recurrence provokes more emotional distress than the original diagnosis (Holland, 1977). However, Lloyd (1979) and Rosch (1981) suggest that cancer patients are chronically stressed by the constant threat of recurrence. A study by Croyle et al. (1997) on the psychological responses to BRCA1 mutation testing concluded that the experience of a cancer diagnosis lessens the psychological distress in mutation carriers. This may be because these women experienced greater cancer-related distress at diagnosis, and therefore mutation testing in that context may moderate the psychological reaction. However, the authors suggest that these data may underestimate the distress
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experienced by individuals undergoing mutation testing where comprehensive preand posttest counseling is not available. In view of the lack of definitive data about range of psychological reactions and impact of mutation testing for the affected relative, it is important to offer comprehensive pretest counseling. A further consideration in offering presymptomatic testing to affected individuals in a family is the maintenance of a healthy concept of self. Many cancer patients who have developed a sporadic cancer are able to separate their self from the disease in that they are a person who has cancer, whereas individuals who have inherited a BRCA1/2 susceptibility gene may perceive themselves as cancer patients due to their predetermined genotype (Croyle et al., 1997). Finally Case Histories 1 and 3 identify the potential for "coercion" and "a sense of duty." Dudok de Wit et al. (1997) highlight the difficulties of disseminating information about mutation analysis and the involvement of affected individuals for predictive testing. In their case history, they report that the affected individual felt like a "guinea pig," that the professionals were not interested in her as a person, and that their concern was only for the predictive value of her DNA. A similar situation is reflected in Case History 3, where there is risk of coercion from the at-risk sister and a perceived sense of filial duty to undertake mutation testing which may override the concerns and implications for her affected sister. In effect, affected individuals may be induced to feel it is their duty to help the at-risk individual at the expense of their psychological and emotional coping strategies. These ethical issues of autonomy, justice, and nonmaleficence are important considerations not only for informed consent, but for the ethos of genetic counseling. In conclusion, the case histories highlight the similarities and differences in implications for the at-risk individual and the affected relative. These complex issues merit the provision of comprehensive pre- and posttest counseling and support, for both patient groups. From our own experiences so far, we can make some suggestions: • Affected family members should be seen by the local genetic service. If outside the area served by the initiating genetics unit, then arrangements should be made with that individual's local genetic service for the collection of samples, counseling, and support. Some genetic centers throughout the UK have developed an agreed liaison policy and reciprocal arrangements for the collection of blood samples and genetic counseling support services. If such a local genetic service is not possible, then the affected individual should be encouraged to nominate a professional support person, perhaps the oncologist or GP. Such person should then be supplied with educational and support backup from the initiating genetic service. Wherever possible, a referral to a clinical genetics service is preferable to try to maintain a "family"-based approach, coordinating the care of the affected individuals and their family members.
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• Affected individuals should be contacted only via the at-risk family member so that no unexpected contact is made by health professionals. The individual requesting testing should coordinate most communications within the family, for example, requesting consent to release clinical notes. "Highrisk" individuals who have an appropriate family structure and, following presymptomatic testing counseling, wish to proceed with DNA testing are asked to contact a living affected relative to obtain her permission to be contacted. Once this permission has been received, the genetic nurse specialist contacts the affected individual to obtain written informed consent, and to obtain a blood sample for BRCA1/2 DNA mutation analysis. • Counseling and information for the affected family member should cover the many medical, ethical, psychosocial, and practical areas (Chadwick and Ngwena, 1992). • Adequate follow-up for the affected family member should be confirmed to be in place, perhaps with an agreed-on health professional coordinating the screening and management. CONCLUSIONS We suggest that testing a family member with cancer for predisposing genes requires careful consideration. Where possible individual counseling and information should be given. Sometimes long-term follow-up is necessary. We are concerned that in the rush to offer testing to women at risk, the concerns of the affected family member, who must be tested first (in most protocols), may be lost because of a lack of service resources or the enthusiasm for research. ACKNOWLEDGMENTS L. France funded by ICRF, J. Gray funded by NHS(Wales) R&D, and now Tenovus the Cancer Charity, K. Brain and C. Anglim funded by MRC.
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