Navigating ethical challenges of integrating genomic medicine into clinical practice: Maximising beneficence in precision oncology

Main Article Content

M J Kotze
K A Grant
N C van der Merwe
N W Barsdorf
M Kruger

Abstract





The development of gene expression profiling and next-generation sequencing technologies have steered oncogenomics to the forefront of precision medicine. This created a need for harmonious cooperation between clinicians and researchers to increase access to precision oncology, despite multiple implementation challenges being encountered. The aim is to apply personalised treatment strategies early in cancer management, targeting tumour subtypes and actionable gene variants within the individual’s broader clinical risk profile and wellbeing. A knowledge-generating database linked to the South African Medical Research Council’s Genomic Centre has been created for the application of personalised medicine, using an integrated service and research approach. Insights gained from patient experiences related to tumour heterogeneity, access to targeted therapies and incidental findings of pathogenic germline variants in tumour DNA, provided practice-changing evidence for the implementation of a cost-minimisation pathology-supported genetic testing strategy. Integrating clinical care with genomic research through data sharing advances personalised medicine and maximises precision oncology benefits.





Article Details

How to Cite
Navigating ethical challenges of integrating genomic medicine into clinical practice: Maximising beneficence in precision oncology. (2024). South African Journal of Bioethics and Law, 17(1), e2071. https://doi.org/10.7196/sajbl.2024.v17i1.2071
Section
Research Articles
Author Biographies

M J Kotze, Division of Chemical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University; and the National Health Laboratory Service, Tygerberg Hospital, Cape Town, South Africa

Prof Maritha Kotze is a principal medical scientist focused on addressing the ethical challenges and knowledge gaps created by the implementation of genomic medicine in clinical practice, through the establishment of a pathology-supported genetic testing platform that enables the integration of research and service delivery in training program design.

K A Grant , Department of Biomedical Sciences, Faculty of Health and Wellness, Cape Peninsula University of Technology, Cape Town, South Africa

Dr Kathleen Grant is a senior lecturer committed to advancing medical knowledge, with a particular interest is tumour genetics of breast carcinomas and translational research exploring microRNA expression as potential biomarkers for early diagnosis and treatment of disease, while maintaining a strong commitment to ethical principles in laboratory medicine.  

N C van der Merwe, Division of Human Genetics, School of Pathology, Faculty of Health Sciences, University of the Free State, South Africa; and the National Health Laboratory Service, Universitas Hospital, Bloemfontein, South Africa

Dr Nerina van der Merwe is principal medical scientist and member of the Ethics Committee of the University of the Free State, with translational research and diagnostics in the field of breast and ovarian cancer as her main interests to ultimately provide better testing strategies for patients in the public healthcare sector.

N W Barsdorf, Office of Research Integrity and Ethics, Division for Research Development, Stellenbosch University, Stellenbosch, South Africa

Dr Nicola Barsdorf is an ethicist specialising in research ethics, qualitative research, international research ethics, global research resources, and distributive justice as key principles applied in the development and introduction of an ethics framework for health technology assessment using the South African Values and Ethics for Universal Health Coverage (SAVE-UHC) Approach.

M Kruger, Department of Paediatrics and Child Health and Human Research Ethics Committee 2, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

Prof Mariana Kruger is a paediatric oncologist, and ethicist, serving as chair of the Health Research Ethics Committee (HREC) 2, Stellenbosch University, clinical member of the Advisory Clinical Committee of SAHPRA, co-director of the Fogarty funded South African Research Ethics Training Initiative Leadership programme at UKZN and international discipline related organizations

How to Cite

Navigating ethical challenges of integrating genomic medicine into clinical practice: Maximising beneficence in precision oncology. (2024). South African Journal of Bioethics and Law, 17(1), e2071. https://doi.org/10.7196/sajbl.2024.v17i1.2071

References

Horak P, Fröhling S, Glimm H. Integrating next-generation sequencing into clinical oncology: strategies, promises and pitfalls. ESMO Open 2016;1(5):1-11. https://doi.org/10.1136/esmoopen-2016-000094

Martin-Romano P, Mezquita L, Hollebecque A, et al. Implementing the European Society for Medical Oncology scale for clinical actionability of molecular targets in a comprehensive profiling program: Impact on precision medicine oncology. JCO Precis Oncol 2022;6:1-11. https://doi.org/10.1200/PO.21.00484

McCourt CM, Boyle D, James J, Salto-Tellez M. Immunohistochemistry in the era of personalised medicine. J Clin Pathol 2013;66(1):58-61. https://doi.org/10.1136/ jclinpath-2012-201140

Nagahashi M, Shimada Y, Ichikawa H, et al. Next-generation sequencing-based gene panel tests for the management of solid tumors. Cancer Sci. 2019;110(1):6-15. https://doi.org/10.1111/cas.13837

Munyaradzi M. Critical reflections on the principle of beneficence in biomedicine. Pan Afr Med J 2012;11:29.

Mateo J, Steuten L, Aftimos P, et al. Delivering precision oncology to patients with cancer. Nat Med 2022;28:658-665. https://doi.org/10.1038/s41591-022-01717-2

Mansinho A, Fernandes RM, Carneiro AV. Histology-agnostic drugs: a paradigm

shift- a narrative review. Adv Ther 2023;40(4):1379-1392. https://doi.org/10.1007/

s12325- 022-02362-4

Riedl JM, Moik F, Esterl T, Kostmann SM, Gerger A, Jost PJ. Molecular diagnostics tailoring personalised cancer therapy-an oncologist‘s view. Virchows Arch. 2023;Nov 20. https://doi.org/10.1007/s00428-023-03702-7

Sarkar S, Deyoung T, Ressler H, Chandler W. Brain tumors: development, drug resistance, and sensitisation - An epigenetic approach. Epigen 2023;18(1):2237761. https://doi.org/10.1080/15592294.2023.2237761

Marchant G, Barnes M, Evans JP, LeRoy B, Wolf SM. From genetics to genomics: facing the liability implications in clinical care. J Law Med Ethics 2020;48(1):11-43. https://doi.org/10.1177/1073110520916994

Guerra CE, Sharma PV, Castillo BS. Multi-cancer early detection: The new frontier in cancer early detection. Annu Rev Med 2024;75:67-81. https://doi.org/10.1146/ annurev- med-050522-033624

Jongeneel CV, Kotze MJ, Bhaw-Luximon A, et al. A view on genomic medicine activities in Africa: implications for policy. Front Genet 2022;13:769919. https://doi. org/10.3389/fgene.2022.769919

Owolabi P, Adam Y, Adebiyi E. Personalizing medicine in Africa: Current state, progress and challenges. Front Genet 2023;14:1233338. https://doi.org/10.3389/ fgene.2023.1233338

Kotze MJ, van Velden DP, Botha K, et al. Pathology-supported genetic testing directed at shared disease pathways for optimised health in later life. Pers Med 2013;10(5):497-507. https://doi.org/10.2217/pme.13.43

Okunola AO, Baatjes KJ, Zemlin AE, et al. Pathology-supported genetic testing for the application of breast cancer pharmacodiagnostics: family counselling, lifestyle adjustments and change of medication. Expert Rev Mol Diagn 2023;23(5):431-443. https://doi.org/10.1080/14737159.2023.2203815

van der Merwe NC, Combrink HM, Ntaita KS, Oosthuizen J. Prevalence of clinically relevant germline BRCA variants in a large unselected South African breast and ovarian cancer cohort: a public sector experience. Front Genet 2022;13:834265. https://doi.org/10.3389/fgene.2022.834265

Ragupathi A, Singh M, Perez AM, Zhang D. Targeting the BRCA1/2 deficient cancer with PARP inhibitors: Clinical outcomes and mechanistic insights. Front Cell Dev Biol 2023;11:1133472. https://doi.org/10.3389/fcell.2023.1133472

Astras G, Papagiannopoulos CI, Kyritsis KA, Markitani C, Vizirianakis IS. Pharmacogenomic testing to guide personalised cancer medicine decisions in private oncology practice: a case study. Front Oncol 2020;28(10):521. https:// doi.org/10.3389/fonc.2020.00521

Gupta S, Smith TR, Broekman ML. Ethical considerations of neuro-oncology trial design in the era of precision medicine. J Neurooncol 2017;134(1):1-7. https://doi. org/10.1007/s11060-017-2502-0

Grant KA, Apffelstaedt JP, Wright C, et al. MammaPrint Pre-screen Algorithm (MPA) reduces chemotherapy in patients with early-stage breast cancer. S Afr Med J 2013;3;103(8):522-526. https://doi.org/10.7196/samj.7223

Grant KA, Pienaar FM, Brundyn K, et al. Incorporating microarray assessment of HER2 status in clinical practice supports individualised therapy in early-stage breast cancer. Breast 2015;24(2):137-142. https://doi.org/10.1016/j.breast.2014.12.006

Grant KA, Myburgh EJ, Murray E, et al. Reclassification of early-stage breast cancer into treatment groups by combining the use of immunohistochemistry and microarray analysis. SA J Science 2019;115(3/4):51-56. https://doi.org/10.17159/ sajs.2019/5461

Kotze MJ. Gknowmix.com: A gateway to genomic healthcare. In: New Life Sciences: Future prospects: BioVisionAlexandria2010 / Bibliotheca Alexandrina; Editors, Ismail Serageldin, Ehsan Masood, with Mohamed El-Faham and Marwa El-Wakil. – Alexandria, Egypt: Bibliotheca Alexandrina, 2011, pp 435-443. https://www. bibalex.org/BiovisionAlexandria/Attachment/Attachment/file/BVA2010Web.pdf

Mampunye L, van der Merwe NC, Grant KA, et al. Pioneering BRCA1/2 point-of- care testing for integration of germline and tumor genetics in breast cancer risk management: A vision for the future of translational pharmacogenomics. Front Oncol 2021;29(11):619817. https://doi.org/10.3389/fonc.2021.619817

Myburgh EJ, de Jager JJ, Murray E, Grant KA, Kotze MJ, de Klerk H. The cost impact of unselective vs selective MammaPrint testing in early-stage breast cancer in Southern Africa. Breast 2021;59:87-93. https://doi.org/10.1016/j.breast.2021.05.010

van der Merwe NC, Ntaita KS, Stofberg H, Combrink HM, Oosthuizen J, Kotze MJ. Implementation of multigene panel testing for breast and ovarian cancer in South Africa: a step towards excellence in oncology for the public sector. Front Oncol 2023;12:938561. https://doi.org/10.3389/fonc.2022.938561

Nembaware V, Johnston K, Diallo AA, et al. A framework for tiered informed consent for health genomic research in Africa. Nat Genet 2019;51(11):1566-1571. https://doi.org/10.1038/s41588-019-0520-x

Torrorey-Sawe R, van der Merwe N, Mining SK, Kotze MJ. Pioneering informed consent for return of research results to breast cancer patients facing barriers to implementation of genomic medicine: The Kenyan BRCA1/2 testing experience using whole exome sequencing. Front Genet 2020;11(170):1-6. https://doi. org/10.3389/fgene.2020.00170

Ivanisevic T, Sewduth RN. Multi-omics integration for the design of novel therapies and the identification of novel biomarkers. Proteomes 2023;11(4):34. https://doi. org/10.3390/proteomes11040034

Sperber NR, Carpenter JS, Cavallari LH, et al. Challenges and strategies for implementing genomic services in diverse settings: experiences from the Implementing GeNomics In pracTicE (IGNITE) network. BMC Med Genomics 2017;10(1):35. https://doi.org/10.1186/s12920-017-0273-2

Pescia C, Guerini-Rocco E, Viale G, Fusco N. Advances in early breast cancer risk profiling: From histopathology to molecular technologies. Cancers (Basel) 2023;15(22):5430. https://doi.org/10.3390/cancers15225430

Myburgh EJ, Langenhoven L, Grant KA, van der Merwe L, Kotze MJ. Clinical overestimation of HER2 positivity in early estrogen and progesterone receptor- positive breast cancer and the value of molecular subtyping using BluePrint. J Global Oncol 2016;16(3):314-322. https://doi.org/10.1200/JGO.2016.006072

Dabbs DJ, Klein ME, Mohsin SK, Tubbs RR, Shuai Y, Bhargava R. High false-negative rate of HER2 quantitative reverse transcription polymerase chain reaction of the Oncotype DX test: an independent quality assurance study. J Clin Oncol 2011;29(32):4279e85. https://doi.org/10.1200/JCO.2011.34.7963

Bai Q, Lv H, Bao L, et al. Invasive breast cancer with HER2 ≥4.0 and <6.0: Risk classification and molecular typing by a 21-gene expression assay and MammaPrint plus BluePrint testing. Breast Cancer 2023;15:563-575. https://doi.org/10.2147/ BCTT.S420738

Makhetha M, Walters S, Aldous C. The review of genetic screening services and common BRCA1/2 variants among South African breast cancer patients. J Genet Couns 2023; Aug 1. https://doi.org/10.1002/jgc4.1755

NecchiA,RaggiD,GiannatempoP,etal.ExceptionalresponsetoolaparibinBRCA2- altered urothelial carcinoma after PD-L1 inhibitor and chemotherapy failure. Eur J Cancer 2018;(96):128-130. http://doi.org/10.1016/j.ejca.2018.03.021

KuangS,LiH,FengJ,XuS,LeY.CorrelationofBRCA2genemutationandprognosis as well as variant genes in invasive urothelial carcinoma of the bladder. Cancer Biomark 2019;25(2):203-212. http://doi.org/10.3233/CBM-182379

Haan JC, Bhaskaran R, Ellappalayam A, et al. MammaPrint and BluePrint comprehensively capture the cancer hallmarks in early-stage breast cancer patients. Genes Chromosom Cancer 2022;61(3):148-160. http://doi.org/10.1002/ gcc.23014

Hoskins KF, Danciu OC, Ko NY, Calip GS. Association of race/ethnicity and the 21- gene recurrence score with breast cancer-specific mortality among US women. JAMA Oncol 2021;7(3):370-378. http://doi.org/10.1001/jamaoncol.2020.7320

Malope MF, da Rocha JEB, Fieggen KJ, as members of the SASHG Committee. Racial labelling in Human Genetics research in Southern Africa. https://sashg. org/wp- content/uploads/2021/07/Racial-labelling-survey_SASHG_10May21_ website.pdf

Aldrighetti CM, Niemierko A, Van Allen E, Willers H, Kamran SC. Racial and ethnic disparities among participants in precision oncology clinical studies. JAMA Netw Open 2021;4(11):e2133205. http://doi.org/10.1001/ jamanetworkopen.2021.33205

Laes JF, Aftimos P, Barthelemy P, et al. The clinical impact of using complex molecular profiling strategies in routine oncology practice. Oncotarget 2018;9(29):20282-20293. http://doi.org/10.18632/oncotarget.24757

Weiss GJ, Hoff BR, Whitehead RP, et al. Evaluation and comparison of two commercially available targeted next-generation sequencing platforms to assist oncology decision making. Onco Targets Ther 2015;8:959-967. https:// doi.org/10.2147/OTT.S81995

Dickens C, Joffe M, Jacobson J, et al. Stage at breast cancer diagnosis and distance from diagnostic hospital in a peri urban setting: a South African public hospital case series of over 1,000 women. Int J Cancer 2014;135(9):2173-2182. https://doi.org/10.1002/ijc.28861

Espina C, McKenzie F, dos-Santos-Silva I. Delayed presentation and diagnosis of breast cancer in African women: a systematic review. Ann Epidemiol 2017;27(10):659-671. https://doi.org/10.1016/j.annepidem.2017.09.007

Rayne S, Schnippel K, Kruger D, Benn CA, Firnhaber C. Delay to diagnosis and breast cancer stage in an urban South African breast clinic. S Afr Med J 2019;109(3):159-163. https://doi.org/10.7196/SAMJ.2019.v109i3.13283

MoremiKE,ScottCJ,deJagerLJ,PienaarR,ZemlinAE,KotzeMJ.Implementation of a pathology-supported genetic testing framework for return of research results to family members of deceased breast cancer patients with somatic TP53 variants. Breast 2021; 56(1):S64-S65. https://doi.org/10.1016/S0960- 9776(21)00205-8

Baatjes KJ, van der Merwe N, Moremi KE, et al. A rapid point-of-care test kit for improved clinical management of patients with breast cancer and associated co- morbidities: Significance of the MTHFR-homocysteine pathway. Breast 2023;68(1):S33-34. https://doi.org/10.1016/S0960-9776(23)00163-7

Vos S, van Delden JJM, van Diest PJ, Bredenoord AL. Moral duties of genomics researchers: Why personalised medicine requires a collective approach. Trends Genet 2017;33:118-128. https://doi.org/10.1016/j.tig.2016.11.006

Kotze MJ, van Rensburg SJ, Davids M, et al. Translating population risk into personal utility using a mobile phone app for application of genomic medicine integrating service and research in the COVID-19 era. Clin Chem Lab Med 2023;61(special suppl):S754, Abstract P0668. https://doi.org/10.1515/cclm- 2023-7041

van der Merwe N, Peeters AV, Pienaar FM, Bezuidenhout J, van Rensburg SJ, Kotze MJ. Exome Sequencing in a family with luminal-type breast cancer underpinned by variation in the methylation pathway. Int J Mol Sci 2017;18(2):467. https://doi.org/10.3390/ijms18020467

Saelaert M, Mertes H, Moerenhout T, De Baere E, Devisch I. Ethical values supporting the disclosure of incidental and secondary findings in clinical genomic testing: a qualitative study. BMC Med Ethics 2020;21(1):9. https://doi. org/10.1186/s12910-020- 0452-0

Teisberg E, Wallace S, O’Hara S. Defining and implementing value-based health care: A strategic framework. Acad Med 2020;95(5):682-685. https://doi. org/10.1097/ACM.0000000000003122

Herbst M C. Cancer Association of South Africa (CANSA): Fact Sheet on MammaPrint Test. https://cansa.org.za/files/2021/03/Fact-Sheet-on- Mammaprint-Test-March-2021.pdf.

Most read articles by the same author(s)

1 2 3 4 5 6 7 8 > >>