Information Topics of Greatest Interest for Return of Genome Sequencing Results among Women Diagnosed with Breast Cancer at a Young Age
- 320 Downloads
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.
KeywordsGenome sequencing Return of results Patient preferences Information needs Breast cancer
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.
Compliance with Ethical Standards
Conflict of Interest
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.
No animal studies were carried out by the authors for this article.
- 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.CrossRefPubMedGoogle 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.CrossRefGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.PubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle Scholar