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Family Chronicles of Missed Opportunities

Family Chronicles of Missed Opportunities A young man who had received a diagnosis of advanced colon cancer and liver metastases was recently referred to a genetics service for a molecular analysis, and a mutation in a mismatch repair gene was identified. However, records at the molecular analysis laboratory revealed an even more tragic story. Approximately 20 years previously, the patient’s family had undergone genetic testing following diagnosis of a sebaceous carcinoma in an older relative of the patient and the suspicion of Muir-Torre syndrome, a rare familial disorder. The family underwent an extensive consultation session, followed by blood sampling and a molecular analysis of the sebaceous carcinoma biopsy sample. Although the tumor clearly showed microsatellite instability–high activity, no mutation could be identified using the available technology. The family was advised about the need for regular clinical surveillance, as well as routine follow-up colonoscopy and gynecological examinations. Over the next several years, the older relative received diagnoses of colon cancer and multiple skin carcinomas, and another family member developed endometrial cancer. Despite these diagnoses, no further cancer screening or genetic service follow-up was performed in any of the family members until this patient received a diagnosis of advanced colon cancer. Another patient, a woman in her late 30s, was identified as a BRCA mutation carrier after receiving a diagnosis of ovarian cancer during a routine examination. The genetic service counselor was concerned when it became apparent that the patient had a remote female relative who had received a diagnosis more than 10 years earlier of being a carrier of the same mutation, following a diagnosis of breast cancer in her mid-30s. The relative had shared her carrier status with close relatives but not with her more distant family members. The clinicians involved in the care of these families felt a deep sense of failure for the delayed diagnosis of potentially preventable cases of familial cancer. These 2 families had initiated their long journeys with the genetic services in the late 1990s, with the reassurance that identification of deleterious mutations would change the outcome of at-risk future generations. In 1999, 2 possible pathways were envisioned for societal effects of the emerging and rapidly expanding field of human disease genetics.1 In the ideal setting, genetic information could be used to prevent or identify diseases at early stages, thus ameliorating human suffering. Conversely, genetic knowledge could also be abused to harm mutation carriers. New medical technologies with potential untoward effects on individual and societal values should be examined using bioethical principles.2 The most widely used framework, outlined by the principles defined by Beauchamp and Childress,3(pp101-301) incorporates autonomy, nonmaleficence, beneficence, and justice. These principles are considered of equal importance, but at certain periods of sociomedical changes, some may gain more relevance and significance. At the inception of the Human Genome Project, concerns were focused on the potential risks to patient rights and adopting appropriate strategies to ensure protection of these rights. Issues related to autonomy and nonmaleficence principles dealt with informed consent, data protection and privacy, the right to refuse disclosure, and the duty to warn.2,4 Fortunately, little evidence supporting deleterious effects on patient rights was actually demonstrated. Protective legislation at the state and federal levels in the United States and in other countries reduced the potential risks for genetic discrimination. No major psychological adverse effects were observed, but rather, beneficial outcomes of adjustment and empowerment. Genetic counselors gained expertise in resolving familial conflicts, and social opinion leaders who shared their genetic status facilitated public acceptance. The benefit of screening and intervention was proven, altering the natural history of cancer by using highly targeted surveillance and management measures.5 Despite this reassuring outcome, current guidelines and bioethical literature still tend to focus on autonomy and nonmaleficence issues, with less emphasis directed toward enhancing beneficence, justice, and equity. The patterns of interaction between patients and clinicians may have considerable impact on a desired beneficial outcome in genetic consultation processes. The most accepted models of interactions—paternalistic, informative, and deliberative—reflect a changing social balance in the role and responsibilities of the patient in medical decision making. The traditional paternalistic approach is now deemed somewhat obsolete and, in practice, has been gradually replaced by the deliberative model. In this shared-decision approach, much of the responsibility is transferred to the patient’s domain. Professional recommendations are vague regarding accountability and responsibility for action. Whereas they emphasize the proven effectiveness of management strategies and the life-saving implications of identifying individuals at risk, the party in charge of the processes is less clearly defined. In the evolving genetic landscape, the emergence of “genetic malpractice” is playing an important role.6 Boundaries of physician and patient responsibilities are not yet fully legally defined. Possible future legal directions may impose novel obligations on physicians: the responsibility of disclosing risk to relatives, the duty of actively recontacting patients for retesting, or performing retesting of retained DNA samples or other antecedently collected data to identify recently discovered genetic abnormalities. Real-life situations indicate that not all patients and families are sufficiently reliable to carry out the complicated and tedious tasks on their own. Patients often neglect to adhere to their personal surveillance and, even more so, to manage identification and outreach to all family members. Inequity is particularly enhanced among lower socioeconomic classes, whose members are provided with less access to the genetic counseling process. The large knowledge gap between patients and genetic counselors can be a substantial barrier for patients to share in decision making. The traditional ally, the primary practitioner, will not be familiar in most cases with the cutting-edge technology and the complex management of hereditary cancer syndromes.5,6 Consideration of the 2 case histories according to these enunciated principles provides a framework to better understand the unfavorable outcomes. Both of these counseled families had good mutual relationships; thus, concerns of confidentiality or refusal of disclosure did not appear to be factors. There were no discrimination or stigmatization issues. Yet, one family failed to adhere to recommended surveillance and the other failed to warn relatives outside the immediate circle, either disregarding or not fully appreciating their potential risk. The lesson to be learned is that individuals and families differ in their resources and abilities to assimilate what is expected of them, and to behave according to the instructions outlined by clinicians. All patients should have a basic right to share in the benefits from the technological advances in our expanding knowledge of the genetics of human diseases. Genetic services have an obligation to ensure that appropriate measures and safeguards are in place to meet these goals. The shortage of experts in genetics will grow as demands expand, and therefore a subset of patients requiring more intensive follow-up should be identified during the genetic counseling process. The interaction models used to work with patients and their at-risk families need to be flexible. In some instances, a paternalistic approach, with active interventions and directed outreach, remains the most appropriate to avoid the types of tragic outcomes described in our cases herein. More than 100 years before the era of personalized medicine, Leo Tolstoy wrote, in Anna Karenina, “All happy families resemble one another; each unhappy family is unhappy in its own way.” This phrase captures the essence of the tailored approach, addressing the needs and abilities of each of those afflicted families. Back to top Article Information Corresponding Author: Anath A. Flugelman, MD, MPH, Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, 7 Michal St, Haifa, Israel 34642 (cmdanath@clalit.org.il). Published Online: April 14, 2016. doi:10.1001/jamaoncol.2016.0110. Conflict of Interest Disclosures: None reported. References 1. Collins FS. Shattuck lecture—medical and societal consequences of the Human Genome Project. N Engl J Med. 1999;341(1):28-37.PubMedGoogle ScholarCrossref 2. Offit K, Thom P. Ethical and legal aspects of cancer genetic testing. Semin Oncol. 2007;34(5):435-443.PubMedGoogle ScholarCrossref 3. Beauchamp TL, Childress JF. Principles of Biomedical Ethics. 7th ed. New York, NY: Oxford University Press; 2013. 4. Riley BD, Culver JO, Skrzynia C, et al. Essential elements of genetic cancer risk assessment, counseling, and testing: updated recommendations of the National Society of Genetic Counselors. J Genet Couns. 2012;21(2):151-161.PubMedGoogle ScholarCrossref 5. Lynch HT, Lynch PM, Lanspa SJ, Snyder CL, Lynch JF, Boland CR. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet. 2009;76(1):1-18.PubMedGoogle ScholarCrossref 6. Marchant GE, Lindor RA. Personalized medicine and genetic malpractice. Genet Med. 2013;15(12):921-922.PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Oncology American Medical Association

Family Chronicles of Missed Opportunities

JAMA Oncology , Volume 2 (5) – May 1, 2016

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References (6)

Publisher
American Medical Association
Copyright
Copyright © 2016 American Medical Association. All Rights Reserved.
ISSN
2374-2437
eISSN
2374-2445
DOI
10.1001/jamaoncol.2016.0110
Publisher site
See Article on Publisher Site

Abstract

A young man who had received a diagnosis of advanced colon cancer and liver metastases was recently referred to a genetics service for a molecular analysis, and a mutation in a mismatch repair gene was identified. However, records at the molecular analysis laboratory revealed an even more tragic story. Approximately 20 years previously, the patient’s family had undergone genetic testing following diagnosis of a sebaceous carcinoma in an older relative of the patient and the suspicion of Muir-Torre syndrome, a rare familial disorder. The family underwent an extensive consultation session, followed by blood sampling and a molecular analysis of the sebaceous carcinoma biopsy sample. Although the tumor clearly showed microsatellite instability–high activity, no mutation could be identified using the available technology. The family was advised about the need for regular clinical surveillance, as well as routine follow-up colonoscopy and gynecological examinations. Over the next several years, the older relative received diagnoses of colon cancer and multiple skin carcinomas, and another family member developed endometrial cancer. Despite these diagnoses, no further cancer screening or genetic service follow-up was performed in any of the family members until this patient received a diagnosis of advanced colon cancer. Another patient, a woman in her late 30s, was identified as a BRCA mutation carrier after receiving a diagnosis of ovarian cancer during a routine examination. The genetic service counselor was concerned when it became apparent that the patient had a remote female relative who had received a diagnosis more than 10 years earlier of being a carrier of the same mutation, following a diagnosis of breast cancer in her mid-30s. The relative had shared her carrier status with close relatives but not with her more distant family members. The clinicians involved in the care of these families felt a deep sense of failure for the delayed diagnosis of potentially preventable cases of familial cancer. These 2 families had initiated their long journeys with the genetic services in the late 1990s, with the reassurance that identification of deleterious mutations would change the outcome of at-risk future generations. In 1999, 2 possible pathways were envisioned for societal effects of the emerging and rapidly expanding field of human disease genetics.1 In the ideal setting, genetic information could be used to prevent or identify diseases at early stages, thus ameliorating human suffering. Conversely, genetic knowledge could also be abused to harm mutation carriers. New medical technologies with potential untoward effects on individual and societal values should be examined using bioethical principles.2 The most widely used framework, outlined by the principles defined by Beauchamp and Childress,3(pp101-301) incorporates autonomy, nonmaleficence, beneficence, and justice. These principles are considered of equal importance, but at certain periods of sociomedical changes, some may gain more relevance and significance. At the inception of the Human Genome Project, concerns were focused on the potential risks to patient rights and adopting appropriate strategies to ensure protection of these rights. Issues related to autonomy and nonmaleficence principles dealt with informed consent, data protection and privacy, the right to refuse disclosure, and the duty to warn.2,4 Fortunately, little evidence supporting deleterious effects on patient rights was actually demonstrated. Protective legislation at the state and federal levels in the United States and in other countries reduced the potential risks for genetic discrimination. No major psychological adverse effects were observed, but rather, beneficial outcomes of adjustment and empowerment. Genetic counselors gained expertise in resolving familial conflicts, and social opinion leaders who shared their genetic status facilitated public acceptance. The benefit of screening and intervention was proven, altering the natural history of cancer by using highly targeted surveillance and management measures.5 Despite this reassuring outcome, current guidelines and bioethical literature still tend to focus on autonomy and nonmaleficence issues, with less emphasis directed toward enhancing beneficence, justice, and equity. The patterns of interaction between patients and clinicians may have considerable impact on a desired beneficial outcome in genetic consultation processes. The most accepted models of interactions—paternalistic, informative, and deliberative—reflect a changing social balance in the role and responsibilities of the patient in medical decision making. The traditional paternalistic approach is now deemed somewhat obsolete and, in practice, has been gradually replaced by the deliberative model. In this shared-decision approach, much of the responsibility is transferred to the patient’s domain. Professional recommendations are vague regarding accountability and responsibility for action. Whereas they emphasize the proven effectiveness of management strategies and the life-saving implications of identifying individuals at risk, the party in charge of the processes is less clearly defined. In the evolving genetic landscape, the emergence of “genetic malpractice” is playing an important role.6 Boundaries of physician and patient responsibilities are not yet fully legally defined. Possible future legal directions may impose novel obligations on physicians: the responsibility of disclosing risk to relatives, the duty of actively recontacting patients for retesting, or performing retesting of retained DNA samples or other antecedently collected data to identify recently discovered genetic abnormalities. Real-life situations indicate that not all patients and families are sufficiently reliable to carry out the complicated and tedious tasks on their own. Patients often neglect to adhere to their personal surveillance and, even more so, to manage identification and outreach to all family members. Inequity is particularly enhanced among lower socioeconomic classes, whose members are provided with less access to the genetic counseling process. The large knowledge gap between patients and genetic counselors can be a substantial barrier for patients to share in decision making. The traditional ally, the primary practitioner, will not be familiar in most cases with the cutting-edge technology and the complex management of hereditary cancer syndromes.5,6 Consideration of the 2 case histories according to these enunciated principles provides a framework to better understand the unfavorable outcomes. Both of these counseled families had good mutual relationships; thus, concerns of confidentiality or refusal of disclosure did not appear to be factors. There were no discrimination or stigmatization issues. Yet, one family failed to adhere to recommended surveillance and the other failed to warn relatives outside the immediate circle, either disregarding or not fully appreciating their potential risk. The lesson to be learned is that individuals and families differ in their resources and abilities to assimilate what is expected of them, and to behave according to the instructions outlined by clinicians. All patients should have a basic right to share in the benefits from the technological advances in our expanding knowledge of the genetics of human diseases. Genetic services have an obligation to ensure that appropriate measures and safeguards are in place to meet these goals. The shortage of experts in genetics will grow as demands expand, and therefore a subset of patients requiring more intensive follow-up should be identified during the genetic counseling process. The interaction models used to work with patients and their at-risk families need to be flexible. In some instances, a paternalistic approach, with active interventions and directed outreach, remains the most appropriate to avoid the types of tragic outcomes described in our cases herein. More than 100 years before the era of personalized medicine, Leo Tolstoy wrote, in Anna Karenina, “All happy families resemble one another; each unhappy family is unhappy in its own way.” This phrase captures the essence of the tailored approach, addressing the needs and abilities of each of those afflicted families. Back to top Article Information Corresponding Author: Anath A. Flugelman, MD, MPH, Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, 7 Michal St, Haifa, Israel 34642 (cmdanath@clalit.org.il). Published Online: April 14, 2016. doi:10.1001/jamaoncol.2016.0110. Conflict of Interest Disclosures: None reported. References 1. Collins FS. Shattuck lecture—medical and societal consequences of the Human Genome Project. N Engl J Med. 1999;341(1):28-37.PubMedGoogle ScholarCrossref 2. Offit K, Thom P. Ethical and legal aspects of cancer genetic testing. Semin Oncol. 2007;34(5):435-443.PubMedGoogle ScholarCrossref 3. Beauchamp TL, Childress JF. Principles of Biomedical Ethics. 7th ed. New York, NY: Oxford University Press; 2013. 4. Riley BD, Culver JO, Skrzynia C, et al. Essential elements of genetic cancer risk assessment, counseling, and testing: updated recommendations of the National Society of Genetic Counselors. J Genet Couns. 2012;21(2):151-161.PubMedGoogle ScholarCrossref 5. Lynch HT, Lynch PM, Lanspa SJ, Snyder CL, Lynch JF, Boland CR. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet. 2009;76(1):1-18.PubMedGoogle ScholarCrossref 6. Marchant GE, Lindor RA. Personalized medicine and genetic malpractice. Genet Med. 2013;15(12):921-922.PubMedGoogle ScholarCrossref

Journal

JAMA OncologyAmerican Medical Association

Published: May 1, 2016

Keywords: cancer,genetic screening,cancer genetics

There are no references for this article.