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Health Disparities From Future Genetic Research Efforts: Breast Cancer as a Case Study
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Health Disparities From Future Genetic Research Efforts: Breast Cancer as a Case Study Christoph I. Lee, MD; Arash Naeim, MD, PhD
Keywords: health disparities n genetics n research n breast cancer J Natl Med Assoc. 2012;104:390-391 Author Affiliation: Robert Wood Johnson Clinical Scholars Program (Dr Lee) and Jonsson Comprehensive Cancer Center and Department of Medicine (Dr Naeim), David Geffen UCLA School of Medicine, Los Angeles, California. Correspondence: Christoph I. Lee, MD, Robert Wood Johnson Clinical Scholars Program at UCLA, 911 Broxton Ave, Ste 303, Los Angeles, CA 90024 ([email protected]).
C
ultural competence is touted as a strategy for minimizing health disparities by creating an equitable health care system for every patient, regardless of race, ethnicity, or culture.1 Over the last several decades, such an effort has taken root in the breast cancer community with a specific aim of ensuring access to effective screening, diagnostic, and therapeutic tools for all women. Breast cancer mortality has been reduced significantly by advances in imaging-based detection and more effective chemotherapies. Nevertheless, African American women continue to have a higher incidence of and mortality rates from early-onset breast cancer compared to Caucasian women.2 Now, advances in the field of genetics promise to again revolutionize and individualize breast cancer diagnosis and treatment. However, with this promise are also renewed concerns about the possibility of increasing health disparities. Emerging breast cancer registries with genomic database components aim to identify new risk-carrying mutations, gene-targeted diagnostics, and new geneticbased therapies. The future success of these endeavors rests upon the initial recruitment of a diverse patient population, with representation from groups that have a disproportionate burden of disease. The relationship between genomics and the concepts of race and ethnicity is complex and controversial. The heterogeneous prevalence of cancer-related risk factors across different races by itself generates concerns about disparities and the inherent discriminatory nature of genetic testing.3,4 Exacerbating the uncertainty of breast cancer genomics 390 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
is the fact that little is known about the predisposing mutations of minority women due to low participation rates in research studies.5 While we know that up to 10% of breast cancers are hereditary6 and that BRCA1 and BRCA2 account for 40% to 60% of such cases,7 we do not know the proportion of mutation carriers among minority women since almost all BRCA1 and BRCA2 mutation studies have been conducted among upper-class European American survivors.8 Moreover, while BRCA1 and BRCA2 mutations carry a 50% to 85% lifetime risk of breast cancer and a 14% to 60% lifetime risk of ovarian cancer,9 it is uncertain if there are other mutations that confer increased risk that are more prevalent among minorities.10,11 Advanced in breast cancer genomics may lead to more targeted and personalized treatment approaches.12 Positive potential consequences of increased genetic testing include more adherence to screening, appropriate use of chemoprevention, prophylactic mastectomy or oophorectomy,13,14 and increased use of risk assessments for first-degree relatives.15 However, the potential benefits from such endeavors are unlikely to be realized by the majority of mutation carriers until the most prevalent racial, ethnic, economic, and knowledge-based disparities are defined and closed.16 There are already large disparities in regards to the awareness about and the use of available genetic tests for breast cancer. Based on the 2003 National Health Interview Survey, nearly 50% of Caucasians reported having heard of genetic testing for cancer risk, compared to only 33% of African Americans and 21% of Hispanics.17 Even among those with regular access to health care, African Americans are significantly less likely than Caucasians to undergo genetic counseling and testing for breast cancer risk even after adjusting for probability of BRCA1 and BRCA2, risk perception and worry, attitudes about testing, socioeconomic characteristics, and discussions with primary care physicians.5,18 For these and other reasons, experts believe that genomics is an area of medicine where racial disparities will continue to increase.16 To counteract this prediction, it is crucial for the breast cancer community to embrace a culturally competent approach to engage more minority VOL. 104, NOS. 7 & 8, JULY/AUGUST 2012
Preventing disparities from genetic research
women in breast cancer and screening registries. Failure to do so will undoubtedly lead to biased recommendations, deficiencies in patient access and outcomes, and likely increase health disparities since these communities face a disproportionate amount of disease burden.19 Researchers have postulated about explanations for the lower minority genetic research participation, including the loss of control of DNA, stigmatization from potential misuse of genetic information, and unequal access to potential benefits.20,21 There is evidence of mistrust among African Americans given their historically unethical treatment during the infamous Tuskegee study.22,23 There are likely a myriad of other dimensions that affect individuals’ willingness to participate in research, including awareness, understanding, strong cultural beliefs, acceptance, and access that differ across racial/ethnic groups.24,25 However, there remains a paucity of studies aimed at identifying the true barriers and motivators among distinct minority groups and their participation in breast cancer genetic research.26,27 In order to entertain a culturally specific approach towards preventing an increasing health disparities gap, more has to be learned about the racial/ethnic differences regarding patient attitudes and willingness to be part of such registries. Toward this end, there must be increased dialogue at the community level about the genetic basis and markers of breast cancer and why research participation is crucial. Community-based partnerships will be a key component in performing successful qualitative studies that will engage minority women in helping define the specific motivators and barriers for genetic registry participation. We must develop relationships with minority community leaders who can help implement awareness campaigns regarding breast cancer genetics in neighborhoods, schools, and churches. Focus groups and one-on-one interviews are needed to help develop a conceptual framework regarding the decision-making process of minority women to participate or not participate in genetic-based research. These same community-based research partnerships will become the critical avenue for implementing culturally sensitive means of encouraging increased minority participation. In essence, we must find a way for the most underrepresented patient groups to become willing partners in the development of future genetic-based advances in breast cancer care; otherwise, we risk widening a gap that we have spent decades narrowing.
References
1. Betancourt JR, Green AR, Carrillo JE, Park ER. Cultural competence and health care disparities: key perspectives and trends. Health Aff (Millwood). 2005;24:499-505. 2. Aziz H, Hussain F, Sohn C, et al. Early onset of breast carcinoma in African American women with poor prognostic factors. Am J Clin Oncol. 1999;22:436-440. 3. Sankar P, Cho MK, Condit CM, et al. Genetic research and health disparities. JAMA. 2004;291:2985-2989.
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
4. Goldenberg AJ, Hull SC, Wilfond BS, Sharp RR. Patient perspectives on group benefits and harms in genetic research. Public Health Genomics. 2011; 14(3)135-142. 5. Armstrong K, Micco E, Carney A, Stopfer J, Putt M. Racial differences in the use of BRCA1/2 testing among women with a family history of breast or ovarian cancer. JAMA. 2005;293:1729-1736. 6. Lacroix M, Leclercq G. The “portrait” of hereditary breast cancer. Breast Cancer Res Treat. 2005;89:297-304. 7. Chen S, Iversen ES, Friebel T, et al. Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol. 2006;24:863-871. 8. Ashing-Giwa KT, Padilla GV, Tejero JS, Kim J. Breast cancer survivorship in a multiethnic sample: challenges in recruitment and measurement. Cancer. 2004;101:450-465. 9. Thompson D, Easton DF. Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst. 2002;94:1358-1365. 10. John EM, Miron A, Gong G, et al. Prevalence of pathogenic BRCA1 mutation carriers in 5 US racial/ethnic groups. JAMA. 2007;298:2869-2876. 11. Meijers-Heijboer H, van den Ouweland A, Klijn J, et al. Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet. 2002;31:55-59. 12. Guessous I, Gwinn M, Khoury MJ. Genome-wide association studies in pharmacogenomics: untapped potential for translation. Genome Med. 2009;1(4):46. 13. Rebbeck TR, Lynch HT, Neuhausen SL, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002;346:1616-1622. 14. Meijers-Heijboer H, van Geel B, van Putten WL, et al. Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2001;345:159-164. 15. Grann VR, Jacobson JS, Thomason D, Hershman D, Heitjan DF, Neugut AI. Effect of prevention strategies on survival and quality-adjusted survival of women with BRCA1/2 mutations: an updated decision analysis. J Clin Oncol. 2002;20:2520-2529. 16. Hall M, Olopade OI. Confronting genetic testing disparities: knowledge is power. JAMA. 2005;293:1783-1785. 17. Wideroff L, Vadaparampil ST, Breen N, Croyle RT, Freedman AN. Awareness of genetic testing for increased cancer risk in the year 2000 National Health Interview Survey. Community Genet. 2003;6:147-156. 18. Hensley Alford S, McBride CM, Reid RJ, Larson EB, Baxevanis AD, Brody LC. Participation in genetic testing research varies by social group. Public Health Genomics. 2011;14:85-93. 19. Yancey AK, Ortega AN, Kumanyika SK. Effective recruitment and retention of minority research participants. Annu Rev Public Health. 2006;27:1-28. 20. Furr LA. Perceptions of genetics research as harmful to society: differences among samples of African-Americans and European-Americans. Genetic Testing. 2002:25-30. 21. Bates BR, Lynch JA, Bevan JL, Condit CM. Warranted concerns, warranted outlooks: a focus group study of public understandings of genetic research. Soc Sci Med. 2005;60:331-344. 22. Armstrong K, McMurphy S, Dean LT, et al. Differences in the patterns of health care system distrust between blacks and whites. J Gen Intern Med. 2008;23:827-833. 23. Corbie-Smith G, Thomas SB, Williams MV, Moody-Ayers S. Attitudes and beliefs of African Americans toward participation in medical research. J Gen Intern Med. 1999;14:537-546. 24. Brown BA, Long HL, Weitz TA, Milliken N. Challenges of recruitment: focus groups with research study recruiters. Women Health. 2000;31:153-166. 25. Giuliano AR, Mokuau N, Hughes C, et al. Participation of minorities in cancer research: the influence of structural, cultural, and linguistic factors. Ann Epidemiol. 2000;10:S22-S34. 26. Mandelblatt J, Kaufman E, Sheppard VB, et al. Breast cancer prevention in community clinics: will low-income Latina patients participate in clinical trials? Prev Med. 2005;40:611-618. 27. Calderon JL, Baker RS, Fabrega H, et al. An ethno-medical perspective on research participation: a qualitative pilot study. MedGenMed. 2006;8(2):23. n
VOL. 104, NOS. 7 & 8, JULY/AUGUST 2012 391
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Health Disparities From Future Genetic Research Efforts: Breast Cancer as a Case Study Christoph I. Lee, MD; Arash Naeim, MD, PhD
Keywords: health disparities n genetics n research n breast cancer J Natl Med Assoc. 2012;104:390-391 Author Affiliation: Robert Wood Johnson Clinical Scholars Program (Dr Lee) and Jonsson Comprehensive Cancer Center and Department of Medicine (Dr Naeim), David Geffen UCLA School of Medicine, Los Angeles, California. Correspondence: Christoph I. Lee, MD, Robert Wood Johnson Clinical Scholars Program at UCLA, 911 Broxton Ave, Ste 303, Los Angeles, CA 90024 ([email protected]).
C
ultural competence is touted as a strategy for minimizing health disparities by creating an equitable health care system for every patient, regardless of race, ethnicity, or culture.1 Over the last several decades, such an effort has taken root in the breast cancer community with a specific aim of ensuring access to effective screening, diagnostic, and therapeutic tools for all women. Breast cancer mortality has been reduced significantly by advances in imaging-based detection and more effective chemotherapies. Nevertheless, African American women continue to have a higher incidence of and mortality rates from early-onset breast cancer compared to Caucasian women.2 Now, advances in the field of genetics promise to again revolutionize and individualize breast cancer diagnosis and treatment. However, with this promise are also renewed concerns about the possibility of increasing health disparities. Emerging breast cancer registries with genomic database components aim to identify new risk-carrying mutations, gene-targeted diagnostics, and new geneticbased therapies. The future success of these endeavors rests upon the initial recruitment of a diverse patient population, with representation from groups that have a disproportionate burden of disease. The relationship between genomics and the concepts of race and ethnicity is complex and controversial. The heterogeneous prevalence of cancer-related risk factors across different races by itself generates concerns about disparities and the inherent discriminatory nature of genetic testing.3,4 Exacerbating the uncertainty of breast cancer genomics 390 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
is the fact that little is known about the predisposing mutations of minority women due to low participation rates in research studies.5 While we know that up to 10% of breast cancers are hereditary6 and that BRCA1 and BRCA2 account for 40% to 60% of such cases,7 we do not know the proportion of mutation carriers among minority women since almost all BRCA1 and BRCA2 mutation studies have been conducted among upper-class European American survivors.8 Moreover, while BRCA1 and BRCA2 mutations carry a 50% to 85% lifetime risk of breast cancer and a 14% to 60% lifetime risk of ovarian cancer,9 it is uncertain if there are other mutations that confer increased risk that are more prevalent among minorities.10,11 Advanced in breast cancer genomics may lead to more targeted and personalized treatment approaches.12 Positive potential consequences of increased genetic testing include more adherence to screening, appropriate use of chemoprevention, prophylactic mastectomy or oophorectomy,13,14 and increased use of risk assessments for first-degree relatives.15 However, the potential benefits from such endeavors are unlikely to be realized by the majority of mutation carriers until the most prevalent racial, ethnic, economic, and knowledge-based disparities are defined and closed.16 There are already large disparities in regards to the awareness about and the use of available genetic tests for breast cancer. Based on the 2003 National Health Interview Survey, nearly 50% of Caucasians reported having heard of genetic testing for cancer risk, compared to only 33% of African Americans and 21% of Hispanics.17 Even among those with regular access to health care, African Americans are significantly less likely than Caucasians to undergo genetic counseling and testing for breast cancer risk even after adjusting for probability of BRCA1 and BRCA2, risk perception and worry, attitudes about testing, socioeconomic characteristics, and discussions with primary care physicians.5,18 For these and other reasons, experts believe that genomics is an area of medicine where racial disparities will continue to increase.16 To counteract this prediction, it is crucial for the breast cancer community to embrace a culturally competent approach to engage more minority VOL. 104, NOS. 7 & 8, JULY/AUGUST 2012
Preventing disparities from genetic research
women in breast cancer and screening registries. Failure to do so will undoubtedly lead to biased recommendations, deficiencies in patient access and outcomes, and likely increase health disparities since these communities face a disproportionate amount of disease burden.19 Researchers have postulated about explanations for the lower minority genetic research participation, including the loss of control of DNA, stigmatization from potential misuse of genetic information, and unequal access to potential benefits.20,21 There is evidence of mistrust among African Americans given their historically unethical treatment during the infamous Tuskegee study.22,23 There are likely a myriad of other dimensions that affect individuals’ willingness to participate in research, including awareness, understanding, strong cultural beliefs, acceptance, and access that differ across racial/ethnic groups.24,25 However, there remains a paucity of studies aimed at identifying the true barriers and motivators among distinct minority groups and their participation in breast cancer genetic research.26,27 In order to entertain a culturally specific approach towards preventing an increasing health disparities gap, more has to be learned about the racial/ethnic differences regarding patient attitudes and willingness to be part of such registries. Toward this end, there must be increased dialogue at the community level about the genetic basis and markers of breast cancer and why research participation is crucial. Community-based partnerships will be a key component in performing successful qualitative studies that will engage minority women in helping define the specific motivators and barriers for genetic registry participation. We must develop relationships with minority community leaders who can help implement awareness campaigns regarding breast cancer genetics in neighborhoods, schools, and churches. Focus groups and one-on-one interviews are needed to help develop a conceptual framework regarding the decision-making process of minority women to participate or not participate in genetic-based research. These same community-based research partnerships will become the critical avenue for implementing culturally sensitive means of encouraging increased minority participation. In essence, we must find a way for the most underrepresented patient groups to become willing partners in the development of future genetic-based advances in breast cancer care; otherwise, we risk widening a gap that we have spent decades narrowing.
References
1. Betancourt JR, Green AR, Carrillo JE, Park ER. Cultural competence and health care disparities: key perspectives and trends. Health Aff (Millwood). 2005;24:499-505. 2. Aziz H, Hussain F, Sohn C, et al. Early onset of breast carcinoma in African American women with poor prognostic factors. Am J Clin Oncol. 1999;22:436-440. 3. Sankar P, Cho MK, Condit CM, et al. Genetic research and health disparities. JAMA. 2004;291:2985-2989.
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
4. Goldenberg AJ, Hull SC, Wilfond BS, Sharp RR. Patient perspectives on group benefits and harms in genetic research. Public Health Genomics. 2011; 14(3)135-142. 5. Armstrong K, Micco E, Carney A, Stopfer J, Putt M. Racial differences in the use of BRCA1/2 testing among women with a family history of breast or ovarian cancer. JAMA. 2005;293:1729-1736. 6. Lacroix M, Leclercq G. The “portrait” of hereditary breast cancer. Breast Cancer Res Treat. 2005;89:297-304. 7. Chen S, Iversen ES, Friebel T, et al. Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol. 2006;24:863-871. 8. Ashing-Giwa KT, Padilla GV, Tejero JS, Kim J. Breast cancer survivorship in a multiethnic sample: challenges in recruitment and measurement. Cancer. 2004;101:450-465. 9. Thompson D, Easton DF. Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst. 2002;94:1358-1365. 10. John EM, Miron A, Gong G, et al. Prevalence of pathogenic BRCA1 mutation carriers in 5 US racial/ethnic groups. JAMA. 2007;298:2869-2876. 11. Meijers-Heijboer H, van den Ouweland A, Klijn J, et al. Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet. 2002;31:55-59. 12. Guessous I, Gwinn M, Khoury MJ. Genome-wide association studies in pharmacogenomics: untapped potential for translation. Genome Med. 2009;1(4):46. 13. Rebbeck TR, Lynch HT, Neuhausen SL, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002;346:1616-1622. 14. Meijers-Heijboer H, van Geel B, van Putten WL, et al. Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2001;345:159-164. 15. Grann VR, Jacobson JS, Thomason D, Hershman D, Heitjan DF, Neugut AI. Effect of prevention strategies on survival and quality-adjusted survival of women with BRCA1/2 mutations: an updated decision analysis. J Clin Oncol. 2002;20:2520-2529. 16. Hall M, Olopade OI. Confronting genetic testing disparities: knowledge is power. JAMA. 2005;293:1783-1785. 17. Wideroff L, Vadaparampil ST, Breen N, Croyle RT, Freedman AN. Awareness of genetic testing for increased cancer risk in the year 2000 National Health Interview Survey. Community Genet. 2003;6:147-156. 18. Hensley Alford S, McBride CM, Reid RJ, Larson EB, Baxevanis AD, Brody LC. Participation in genetic testing research varies by social group. Public Health Genomics. 2011;14:85-93. 19. Yancey AK, Ortega AN, Kumanyika SK. Effective recruitment and retention of minority research participants. Annu Rev Public Health. 2006;27:1-28. 20. Furr LA. Perceptions of genetics research as harmful to society: differences among samples of African-Americans and European-Americans. Genetic Testing. 2002:25-30. 21. Bates BR, Lynch JA, Bevan JL, Condit CM. Warranted concerns, warranted outlooks: a focus group study of public understandings of genetic research. Soc Sci Med. 2005;60:331-344. 22. Armstrong K, McMurphy S, Dean LT, et al. Differences in the patterns of health care system distrust between blacks and whites. J Gen Intern Med. 2008;23:827-833. 23. Corbie-Smith G, Thomas SB, Williams MV, Moody-Ayers S. Attitudes and beliefs of African Americans toward participation in medical research. J Gen Intern Med. 1999;14:537-546. 24. Brown BA, Long HL, Weitz TA, Milliken N. Challenges of recruitment: focus groups with research study recruiters. Women Health. 2000;31:153-166. 25. Giuliano AR, Mokuau N, Hughes C, et al. Participation of minorities in cancer research: the influence of structural, cultural, and linguistic factors. Ann Epidemiol. 2000;10:S22-S34. 26. Mandelblatt J, Kaufman E, Sheppard VB, et al. Breast cancer prevention in community clinics: will low-income Latina patients participate in clinical trials? Prev Med. 2005;40:611-618. 27. Calderon JL, Baker RS, Fabrega H, et al. An ethno-medical perspective on research participation: a qualitative pilot study. MedGenMed. 2006;8(2):23. n
VOL. 104, NOS. 7 & 8, JULY/AUGUST 2012 391