TOTAL VIEWS: 8125
Background: Pharmacogenomics elucidates the hereditary basis of inter-individual differences in drug responses. Genetic variation influences an individual’s response to a pharmacological treatment. Therefore, pharmacogenomic information can be used to make treatment more effective and safer, allowing a personalised treatment, especially in Oncology. Pharmacogenomics and precision medicine strategies are becoming increasingly prevalent in research and clinical practice. Breast cancer is a heterogeneous disease that can be classified in different subtypes and about 20% to 25% of all breast cancers are HER2-positive. Several studies have established the HER2 receptor as an effective target for the treatment of breast cancer. Objective: The present review aims to survey the available drugs that target the HER2 protein and to elucidate the way in which pharmacogenomics allows to adapt the therapeutic according to the patient’s genetic profile. Methods: A search was conducted using MEDLINE/PubMed and B-on databases. Data were extracted with specific keywords and the inclusion criteria for assessing the studies published between 2013 and 2020. Results: After evaluating the several studies, we included 12 studies in this review. The trastuzumab was the first drug for anti-HER2 therapy and is a reference drug targeting breast cancer. With knowledge ever deeper the genetic patient profile, new drugs have also emerged, like pertuzumab, lapatinib and neratinib, targeting new molecular sites with a different safety and efficacy profile. These drugs can be used alone in combination therapy, which increases the chances of therapeutic success. Conclusion: The personalized medicine based on pharmacogenomic biomarkers allows treatment decisions to be made based on the genotyping of tumors and genetic profiles. Targeting therapy for genetic changes is a promising approach that improves clinical outcomes, in terms of response rates, survival, safety and costs.
[1] Rodríguez-Vicente, A. E., Lumbreras, E., Hernández, J. M., Martín, M., Calles, A., Otín, C. L., et al. (2016). Pharmacogenetics and pharmacogenomics as tools in cancer therapy. Drug Metab Pers Ther., 2016, 31(1): 25-34.
[2] Jeibouei, S., Akbari, M. E., Kalbasi, A., Aref, A. R., Ajoudanian, M., Rezvani, A., et al. (2019). Personalized medicine in breast cancer: Pharmacogenomics approaches. Pharmgenomics Pers Med., 2019, 12: 59-73.
[3] Filipski, K. K., Mechanic, L. E., Long, R., Freedman, A. N. (2014). Pharmacogenomics in oncology care. Front Genet, 2014, 5(APR): 1-5.
[4] Lauschke, V. M., Milani, L., Ingelman-Sundberg, M. (2018). Pharmacogenomic Biomarkers for Improved Drug Therapy—Recent Progress and Future Developments. AAPS J., 2018, 20(1).
[5] Innocenti, F. (2017). Bringing a genomic perspective to the safety of drug treatment in oncology. F1000Research, 2017, 6: 1-5.
[6] Globocan Observatory, W. (2019). Cancer Today—World. Int Agency Res Cancer [Internet], 2019, 876: 2018-9. Available from: https://gco.iarc.fr/today/data/factsheets/populations/900-world-factsheets.pdf.
[7] Wang, J., Xu, B. (2019). Targeted therapeutic options and future perspectives for HER2-positive breast cancer. Signal Transduct Target Ther [Internet], 2019, 4(1). Available from: http://dx.doi.org/10.1038/s41392-019-0069-2.
[8] Mahtani, R., Hineman, L. (2019). Advances in HER2-Positive Breast Cancer: Novel Therapies and Adverse Event Management. J Adv Pract Oncol [Internet], 2019, 10(2): 136-53. Available from: http://www.ncbi.nlm.nih.gov/ pubmed/31538025%0A http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6750923
[9] Zhang, Y., Somtakoune, S. D., Cheung, C., Listiawan, M., Feng, X. (2016). Therapeutic Application of Pharmacogenomics in Oncology. AAPS J [Internet], 2016, 18(4): 819-29. Available from: http://dx.doi.org/10.1208/s12248-016-9926-x.
[10] Kalia, M. (2015). Biomarkers for personalized oncology: Recent advances and future challenges. Metabolism [Internet]. 2015, 64(3): S16-21. Available from: http://dx.doi.org/10.1016/j.metabol.2014.10.027.
[11] Chan, A., Delaloge, S., Holmes, F. A., Moy, B., Iwata, H., Harvey, V. J., et al. (2016). Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol [Internet], 2016, 17(3): 367-77. Available from: http://dx.doi.org/10.1016/ S1470-2045(15)00551-3.
[12] Infarmed. Infomed—Base de dados de medicamentos [Internet]. 2019 [cited 2019 Dec 2]. Available from: http://app7.infarmed.pt/infomed/inicio.php.
[13] Welslau, M., Hartkopf, A. D., Müller, V., Wöckel, A., Lux, M. P., Janni, W., et al. (2019). Update Breast Cancer 2019 Part 5—Diagnostic and Therapeutic Challenges of New, Personalised Therapies in Patients with Advanced Breast Cancer. Geburt-shilfe Frauenheilkd, 2019, 79(10): 1090-9.
[14] Gaibar, M., Beltrán, L., Romero-Lorca, A., Fernández-Santander, A., Novillo, A., Selli, C. (2020). Somatic Mutations in HER2 and Implications for Current Treatment Paradigms in HER2-Positive Breast Cancer. J Oncol., 2020.
[15] Perrier, A., Gligorov, J., Lefèvre, G., Boissan, M. (2018). The extracellular domain of Her2 in serum as a biomarker of breast cancer. Lab Investig [Internet]., 2018, 98(6): 696-707. Available from: http://dx.doi.org/10.1038/s41374-018-0033-8.
[16] Gagliato, D. D. M., Leonardo, D., Jardim, F., Pereira, M. S., Hortobagyi, G. N. (2016). Mechanisms of resistance and sensitivity to anti-HER2 therapies in HER2 + breast cancer Introduction : Pathways to Trastuzumab. Oncotarget., 2016, 7(39).
[17] Mishra, R., Hanker, A. B., Garrett, J. T. (2017). Genomic alterations of ERBB receptors in cancer: Clinical implications. On-cotarget, 2017, 8(69): 114371-92.
[18] Wen, W., Chen, W. S., Xiao, N., Bender, R., Ghazalpour, A., Tan Z, et al. (2015). Mutations in the kinase domain of the HER2/ERBB2 gene identified in a wide variety of human cancers. J Mol Diagnostics [Internet], 2015, 17(5): 487-95. Available from: http://dx.doi.org/10.1016/j.jmoldx.2015.04.003.
Pharmacogenomic Application in HER2-positive Breast Cancer
How to cite this paper: Ana Guedes, Célia A. Gomes, Sara Martins, Rui Cruz. (2021) Pharmacogenomic Application in HER2-positive Breast Cancer. International Journal of Clinical and Experimental Medicine Research, 5(4), 490-497.
DOI: http://dx.doi.org/10.26855/ijcemr.2021.10.011