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Information Topics of Greatest Interest for Return of Genome Sequencing Results among Women Diagnosed with Breast Cancer at a Young Age

Journal of Genetic Counseling

Abstract

We investigated what information women diagnosed with breast cancer at a young age would want to learn when genome sequencing results are returned. We conducted 60 semi-structured interviews with women diagnosed with breast cancer at age 40 or younger. We examined what specific information participants would want to learn across result types and for each type of result, as well as how much information they would want. Genome sequencing was not offered to participants as part of the study. Two coders independently coded interview transcripts; analysis was conducted using NVivo10. Across result types, participants wanted to learn about health implications, risk and prevalence in quantitative terms, causes of variants, and causes of diseases. Participants wanted to learn actionable information for variants affecting risk of preventable or treatable disease, medication response, and carrier status. The amount of desired information differed for variants affecting risk of unpreventable or untreatable disease, with uncertain significance, and not health-related. Women diagnosed with breast cancer at a young age recognize the value of genome sequencing results in identifying potential causes and effective treatments and expressed interest in using the information to help relatives and to further understand their other health risks. Our findings can inform the development of effective feedback strategies for genome sequencing that meet patients’ information needs and preferences.

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References

  • Anders, C. K., Hsu, D. S., Broadwater, G., Acharya, C. R., Foekens, J. A., Zhang, Y., et al. (2008). Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. Journal of Clinical Oncology, 26(20), 3324–3330. doi:10.1200/jco.2007.14.2471.

    Article  PubMed  Google Scholar 

  • Anders, C. K., Johnson, R., Litton, J., Phillips, M., & Bleyer, A. (2009). Breast cancer before age 40 years. Seminars in Oncology, 36(3), 237–249. doi:10.1053/j.seminoncol.2009.03.001.

    Article  PubMed  PubMed Central  Google Scholar 

  • Assi, H. A., Khoury, K. E., Dbouk, H., Khalil, L. E., Mouhieddine, T. H., & El Saghir, N. S. (2013). Epidemiology and prognosis of breast cancer in young women. Journal of Thoracic Disease, 5(Suppl 1), S2–S8. doi:10.3978/j.issn.2072-1439.2013.05.24.

    PubMed  PubMed Central  Google Scholar 

  • Biesecker, L. G., & Green, R. C. (2014). Diagnostic clinical genome and exome sequencing. The New England Journal of Medicine, 370(25), 2418–2425. doi:10.1056/NEJMra1312543.

    Article  PubMed  Google Scholar 

  • Bonadona, V., Sinilnikova, O. M., Chopin, S., Antoniou, A. C., Mignotte, H., Mathevet, P., et al. (2005). Contribution of BRCA1 and BRCA2 germ-line mutations to the incidence of breast cancer in young women: results from a prospective population-based study in France. Genes, Chromosomes & Cancer, 43(4), 404–413. doi:10.1002/gcc.20199.

    Article  CAS  Google Scholar 

  • Bredenoord, A. L., Kroes, H. Y., Cuppen, E., Parker, M., & van Delden, J. J. (2011). Disclosure of individual genetic data to research participants: the debate reconsidered. Trends in Genetics, 27(2), 41–47. doi:10.1016/j.tig.2010.11.004.

    Article  CAS  PubMed  Google Scholar 

  • Caulfield, T., McGuire, A. L., Cho, M., Buchanan, J. A., Burgess, M. M., Danilczyk, U., et al. (2008). Research ethics recommendations for whole-genome research: consensus statement. PLoS Biology, 6(3), e73. doi:10.1371/journal.pbio.0060073.

    Article  PubMed  PubMed Central  Google Scholar 

  • Christenhusz, G. M., Devriendt, K., Peeters, H., Van Esch, H., & Dierickx, K. (2014). The communication of secondary variants: interviews with parents whose children have undergone array-CGH testing. Clinical Genetics, 86(3), 207–216. doi:10.1111/cge.12354.

    Article  CAS  PubMed  Google Scholar 

  • Crouch, J., Yu, J. H., Shankar, A. G., & Tabor, H. K. (2015). “We don’t know her history, her background”: adoptive parents’ perspectives on whole genome sequencing results. Journal of Genetic Counseling, 24(1), 67–77. doi:10.1007/s10897-014-9738-z.

    Article  PubMed  Google Scholar 

  • Cybulski, C., Wokolorczyk, D., Jakubowska, A., Huzarski, T., Byrski, T., Gronwald, J., et al. (2011). Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer. Journal of Clinical Oncology, 29(28), 3747–3752. doi:10.1200/jco.2010.34.0778.

    Article  CAS  PubMed  Google Scholar 

  • Desmond, A., Kurian, A. W., Gabree, M., Mills, M. A., Anderson, M. J., Kobayashi, Y., et al. (2015). Clinical actionability of multigene panel testing for hereditary breast and ovarian cancer risk assessment. JAMA Oncology, 1(7), 943–951. doi:10.1001/jamaoncol.2015.2690.

    Article  PubMed  Google Scholar 

  • Dressler, L. G. (2009a). Biobanking and disclosure of research results: Addressing the tension between professional boundaries and moral intuition. In J. H. Solbakk, S. Holm, & B. Hofmann (Eds.), The ethics of research biobanking (pp. 85–99). New York: Springer.

    Chapter  Google Scholar 

  • Dressler, L. G. (2009b). Disclosure of research results from cancer genomic studies: state of the science. Clinical Cancer Research, 15(13), 4270–4276. doi:10.1158/1078-0432.CCR-08-3067.

    Article  PubMed  Google Scholar 

  • Ellis, M. J., Ding, L., Shen, D., Luo, J., Suman, V. J., Wallis, J. W., & Mardis, E. R. (2012). Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature, 486(7403), 353–360. doi:10.1038/nature11143.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Facio, F. M., Brooks, S., Loewenstein, J., Green, S., Biesecker, L. G., & Biesecker, B. B. (2011). Motivators for participation in a whole-genome sequencing study: implications for translational genomics research. European Journal of Human Genetics, 19(12), 1213–1217. doi:10.1038/ejhg.2011.123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fredholm, H., Eaker, S., Frisell, J., Holmberg, L., Fredriksson, I., & Lindman, H. (2009). Breast cancer in young women: poor survival despite intensive treatment. PloS One, 4(11), e7695. doi:10.1371/journal.pone.0007695.

    Article  PubMed  PubMed Central  Google Scholar 

  • Golshan, M., Miron, A., Nixon, A. J., Garber, J. E., Cash, E. P., Iglehart, J. D., & Wong, J. S. (2006). The prevalence of germline BRCA1 and BRCA2 mutations in young women with breast cancer undergoing breast-conservation therapy. American Journal of Surgery, 192(1), 58–62. doi:10.1016/j.amjsurg.2005.12.005.

    Article  CAS  PubMed  Google Scholar 

  • Gray, S. W., Hicks-Courant, K., Cronin, A., Rollins, B. J., & Weeks, J. C. (2014). Physicians’ attitudes about multiplex tumor genomic testing. Journal of Clinical Oncology, 32(13), 1317–1323. doi:10.1200/JCO.2013.52.4298.

    Article  PubMed  PubMed Central  Google Scholar 

  • Green, R. C., Berg, J. S., Grody, W. W., Kalia, S. S., Korf, B. R., Martin, C. L., & Genomics (2013). ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genetics in Medicine, 15(7), 565–574. doi:10.1038/gim.2013.73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Green, R. C., Goddard, K. A., Jarvik, G. P., Amendola, L. M., Appelbaum, P. S., Berg, J. S., et al. (2016). Clinical sequencing exploratory research consortium: accelerating evidence-based practice of genomic medicine. American Journal of Human Genetics, 98(6), 1051–1066. doi:10.1016/j.ajhg.2016.04.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guba, E. G., & Lincoln, Y. S. (1994). Competing paradigms in qualitative research. In N. K. Denzin & Y. S. Lincoln (Eds.), Handbook of qualitative research (pp. 105–117). Thousand Oaks: Sage.

    Google Scholar 

  • Heemskerk-Gerritsen, B. A., Rookus, M. A., Aalfs, C. M., Ausems, M. G., Collee, J. M., Jansen, L., et al. (2015). Improved overall survival after contralateral risk-reducing mastectomy in BRCA1/2 mutation carriers with a history of unilateral breast cancer: a prospective analysis. International Journal of Cancer, 136(3), 668–677. doi:10.1002/ijc.29032.

    CAS  PubMed  Google Scholar 

  • Hitch, K., Joseph, G., Guiltinan, J., Kianmahd, J., Youngblom, J., & Blanco, A. (2014). Lynch syndrome patients’ views of and preferences for return of results following whole exome sequencing. Journal of Genetic Counseling, 23(4), 539–551. doi:10.1007/s10897-014-9687-6.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hsieh, H. F., & Shannon, S. E. (2005). Three approaches to qualitative content analysis. Qualitative Health Research, 15(9), 1277–1288. doi:10.1177/1049732305276687.

    Article  PubMed  Google Scholar 

  • Ingham, S. L., Sperrin, M., Baildam, A., Ross, G. L., Clayton, R., Lalloo, F., et al. (2013). Risk-reducing surgery increases survival in BRCA1/2 mutation carriers unaffected at time of family referral. Breast Cancer Research and Treatment, 142(3), 611–618. doi:10.1007/s10549-013-2765-x.

    Article  CAS  PubMed  Google Scholar 

  • Institute of Medicine (2001). Crossing the quality chasm: A new health system for the 21st century. Washington, D.C.: National Academies Press.

    Google Scholar 

  • Jamal, S. M., Yu, J. H., Chong, J. X., Dent, K. M., Conta, J. H., Tabor, H. K., & Bamshad, M. J. (2013). Practices and policies of clinical exome sequencing providers: analysis and implications. American Journal of Medical Genetics. Part A, 161A(5), 935–950. doi:10.1002/ajmg.a.35942.

    Article  PubMed  Google Scholar 

  • Janatova, M., Kleibl, Z., Stribrna, J., Panczak, A., Vesela, K., Zimovjanova, M., et al. (2013). The PALB2 gene is a strong candidate for clinical testing in BRCA1- and BRCA2-negative hereditary breast cancer. Cancer Epidemiology, Biomarkers & Prevention, 22(12), 2323–2332. doi:10.1158/1055-9965.epi-13-0745-t.

    Article  CAS  Google Scholar 

  • Johnson, R. H., Chien, F. L., & Bleyer, A. (2013). Incidence of breast cancer with distant involvement among women in the United States, 1976 to 2009. JAMA, 309(8), 800–805. doi:10.1001/jama.2013.776.

    Article  CAS  PubMed  Google Scholar 

  • Kaphingst, K. A., McBride, C. M., Wade, C., Alford, S. H., Brody, L. C., & Baxevanis, A. D. (2010). Consumers’ use of web-based information and their decisions about multiplex genetic susceptibility testing. Journal of Medical Internet Research, 12(3), e41. doi:10.2196/jmir.1587.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kaphingst, K. A., Ivanovich, J., Biesecker, B. B., Dresser, R., Seo, J., Dressler, L. G., & Goodman, M. S. (2016). Preferences for return of incidental findings from genome sequencing among women diagnosed with breast cancer at a young Age. Clinical Genetics, 89(3), 378–384. doi:10.1111/cge.12597.

    Article  CAS  PubMed  Google Scholar 

  • Leventhal, K. G., Tuong, W., Peshkin, B. N., Salehizadeh, Y., Fishman, M. B., Eggly, S., et al. (2013). “Is it really worth it to get tested?”: primary care patients’ impressions of predictive SNP testing for colon cancer. Journal of Genetic Counseling, 22(1), 138–151. doi:10.1007/s10897-012-9530-x.

    Article  PubMed  Google Scholar 

  • Manolio, T. A., Chisholm, R. L., Ozenberger, B., Roden, D. M., Williams, M. S., Wilson, R., et al. (2013). Implementing genomic medicine in the clinic: the future is here. Genetics in Medicine, 15(4), 258–267. doi:10.1038/gim.2012.157.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mardis, E. R. (2008). The impact of next-generation sequencing technology on genetics. Trends in Genetics, 24(3), 133–141. doi:10.1016/j.tig.2007.12.007.

    Article  CAS  PubMed  Google Scholar 

  • Matsui, K., Lie, R. K., Kita, Y., & Ueshima, H. (2008). Ethics of future disclosure of individual risk information in a genetic cohort study: a survey of donor preferences. Journal of Epidemiology, 18(5), 217–224.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mavaddat, N., Peock, S., Frost, D., Ellis, S., Platte, R., Fineberg, E., et al. (2013). Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. Journal of the National Cancer Institute, 105(11), 812–822. doi:10.1093/jnci/djt095.

    Article  CAS  PubMed  Google Scholar 

  • McGuire, A. L., & Lupski, J. R. (2010). Personal genome research : what should the participant be told? Trends in Genetics, 26(5), 199–201. doi:10.1016/j.tig.2009.12.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McLaughlin, H. M., Ceyhan-Birsoy, O., Christensen, K. D., Kohane, I. S., Krier, J., Lane, W. J., & MedSeq, P. (2014). A systematic approach to the reporting of medically relevant findings from whole genome sequencing. BMC Medical Genetics, 15, 134. doi:10.1186/s12881-014-0134-1.

    Article  PubMed  PubMed Central  Google Scholar 

  • Murphy, J., Scott, J., Kaufman, D., Geller, G., LeRoy, L., & Hudson, K. (2008). Public expectations for return of results from large-cohort genetic research. The American Journal of Bioethics, 8(11), 36–43. doi:10.1080/15265160802513093.

    Article  PubMed  PubMed Central  Google Scholar 

  • O’Daniel, J., & Haga, S. B. (2011). Public perspectives on returning genetics and genomics research results. Public Health Genomics, 14, 346–355. doi:10.1159/000324933.

    Article  PubMed  PubMed Central  Google Scholar 

  • O’Neill, S. C., Lipkus, I. M., Sanderson, S. C., Shepperd, J., Docherty, S., & McBride, C. M. (2013). Motivations for genetic testing for lung cancer risk among young smokers. Tobacco Control, 22(6), 406–411. doi:10.1136/tobaccocontrol-2011-050306.

    Article  PubMed  Google Scholar 

  • Pasche, B., & Absher, D. (2011). Whole-genome sequencing: a step closer to personalized medicine. JAMA, 305(15), 1596–1597. doi:10.1001/jama.2011.484.

    Article  CAS  PubMed  Google Scholar 

  • Renwick, A., Thompson, D., Seal, S., Kelly, P., Chagtai, T., Ahmed, M., et al. (2006). ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nature Genetics, 38(8), 873–875. doi:10.1038/ng1837.

    Article  CAS  PubMed  Google Scholar 

  • Riedl, C. C., Slobod, E., Jochelson, M., Morrow, M., Goldman, D. A., Gonen, M., & Ulaner, G. A. (2014). Retrospective analysis of 18F-FDG PET/CT for staging asymptomatic breast cancer patients younger than 40 years. Journal of Nuclear Medicine, 55(10), 1578–1583. doi:10.2967/jnumed.114.143297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rutten, L. J., Arora, N. K., Bakos, A. D., Aziz, N., & Rowland, J. (2005). Information needs and sources of information among cancer patients: a systematic review of research (1980–2003). Patient Education and Counseling, 57(3), 250–261. doi:10.1016/j.pec.2004.06.006.

    Article  PubMed  Google Scholar 

  • Schmidlen, T. J., Wawak, L., Kasper, R., Garcia-Espana, J. F., Christman, M. F., & Gordon, E. S. (2014). Personalized genomic results: analysis of informational needs. Journal of Genetic Counseling, 23(4), 578–587. doi:10.1007/s10897-014-9693-8.

    Article  PubMed  Google Scholar 

  • Selkirk, C. G., Weissman, S. M., Anderson, A., & Hulick, P. J. (2013). Physicians’ preparedness for integration of genomic and pharmacogenetic testing into practice within a major healthcare system. Genetic Testing and Molecular Biomarkers, 17(3), 219–225. doi:10.1089/gtmb.2012.0165.

    Article  PubMed  Google Scholar 

  • Sharp, R. R. (2011). Downsizing genomic medicine: approaching the ethical complexity of whole-genome sequencing by starting small. Genetics in Medicine, 13(3), 191–194. doi:10.1097/GIM.0b013e31820f603f.

    Article  PubMed  Google Scholar 

  • Sieh, W., Rothstein, J. H., McGuire, V., & Whittemore, A. S. (2014). The role of genome sequencing in personalized breast cancer prevention. Cancer Epidemiology, Biomarkers & Prevention, 23(11), 2322–2327. doi:10.1158/1055-9965.epi-14-0559.

    Article  CAS  Google Scholar 

  • Tabor, H. K., Stock, J., Brazg, T., McMillin, M. J., Dent, K. M., Yu, J. H., et al. (2012). Informed consent for whole genome sequencing: a qualitative analysis of participant expectations and perceptions of risks, benefits, and harms. American Journal of Medical Genetics. Part A, 158A(6), 1310–1319. doi:10.1002/ajmg.a.35328.

    Article  PubMed  PubMed Central  Google Scholar 

  • Taplin, S. H., Anhang Price, R., Edwards, H. M., Foster, M. K., Breslau, E. S., Chollette, V., et al. (2012). Introduction: Understanding and influencing multilevel factors across the cancer care continuum. Journal of the National Cancer Institute. Monographs, 2012(44), 2–10. doi:10.1093/jncimonographs/lgs008.

    Article  PubMed  PubMed Central  Google Scholar 

  • Trujillano, D., Weiss, M. E., Schneider, J., Koster, J., Papachristos, E. B., Saviouk, V., et al. (2015). Next-generation sequencing of the BRCA1 and BRCA2 genes for the genetic diagnostics of hereditary breast and/or ovarian cancer. The Journal of Molecular Diagnostics, 17(2), 162–170. doi:10.1016/j.jmoldx.2014.11.004.

    Article  CAS  PubMed  Google Scholar 

  • Wright, M. F., Lewis, K. L., Fisher, T. C., Hooker, G. W., Emanuel, T. E., Biesecker, L. G., & Biesecker, B. B. (2014). Preferences for results delivery from exome sequencing/genome sequencing. Genetics in Medicine, 16(6), 442–447. doi:10.1038/gim.2013.170.

    Article  PubMed  Google Scholar 

  • Yauch, R. L., & Settleman, J. (2012). Recent advances in pathway-targeted cancer drug therapies emerging from cancer genome analysis. Current Opinion in Genetics & Development, 22(1), 45–49. doi:10.1016/j.gde.2012.01.003.

    Article  CAS  Google Scholar 

  • Yu, J. H., Crouch, J., Jamal, S. M., Bamshad, M. J., & Tabor, H. K. (2014). Attitudes of non-African American focus group participants toward return of results from exome and whole genome sequencing. American Journal of Medical Genetics. Part A, 164A(9), 2153–2160. doi:10.1002/ajmg.a.36610.

    Article  PubMed  Google Scholar 

  • Zardavas, D., Baselga, J., & Piccart, M. (2013). Emerging targeted agents in metastatic breast cancer. Nature Reviews. Clinical Oncology, 10(4), 191–210. doi:10.1038/nrclinonc.2013.29.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Cancer Institute, National Institutes of Health (R01CA168608). This research was also supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health.

The authors would like to thank the women who agreed to participate in the study, and the coders for their valuable assistance in coding interview transcripts.

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Correspondence to Joann Seo.

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Joann Seo, Jennifer Ivanovich, Melody Goodman, Barbara Biesecker, and Kimberly Kaphingst declare that they have no conflict of interest.

Human Studies and Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

Animal Studies

No animal studies were carried out by the authors for this article.

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Seo, J., Ivanovich, J., Goodman, M.S. et al. Information Topics of Greatest Interest for Return of Genome Sequencing Results among Women Diagnosed with Breast Cancer at a Young Age. J Genet Counsel 26, 511–521 (2017). https://doi.org/10.1007/s10897-016-0006-2

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  • DOI: https://doi.org/10.1007/s10897-016-0006-2

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