Nthontho Keneuoe Cecilia, Ndlovu Andrew Khulekani, Sharma Kirthana, Kasvosve Ishmael, Hertz Daniel Louis, Paganotti Giacomo Maria
School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana.
Botswana-University of Pennsylvania Partnership, Gaborone, Botswana.
Pharmgenomics Pers Med. 2022 Jun 21;15:613-652. doi: 10.2147/PGPM.S308531. eCollection 2022.
Breast cancer is the most frequent cause of cancer death in low- and middle-income countries, in particular among sub-Saharan African women, where response to available anticancer treatment therapy is often limited by the recurrent breast tumours and metastasis, ultimately resulting in decreased overall survival rate. This can also be attributed to African genomes that contain more variation than those from other parts of the world. The purpose of this review is to summarize published evidence on pharmacogenetic and pharmacokinetic aspects related to specific available treatments and the known genetic variabilities associated with metabolism and/or transport of breast cancer drugs, and treatment outcomes when possible. The emphasis is on the African genetic variation and focuses on the genes with the highest strength of evidence, with a close look on , and , which are the genes known to play major roles in the metabolism and/or elimination of the respective anti-breast cancer drugs given to the patients. The genetic variability of their metabolism could be associated with different metabolic phenotypes that may cause reduced patients' adherence because of toxicity or sub-therapeutic doses. Finally, this knowledge enhances possible personalized treatment approaches, with the possibility of improving survival outcomes in patients with breast cancer.
在低收入和中等收入国家，乳腺癌是导致癌症死亡的最常见原因，尤其是在撒哈拉以南非洲地区的女性中。在这些地区，复发性乳腺肿瘤和转移常常限制了现有抗癌治疗的效果，最终导致总体生存率下降。这也可能归因于非洲基因组比世界其他地区的基因组含有更多的变异。本综述的目的是总结已发表的关于与特定现有治疗相关的药物遗传学和药代动力学方面的证据，以及与乳腺癌药物代谢和/或转运相关的已知基因变异，以及可能的治疗结果。重点是非洲的基因变异，并关注证据强度最高的基因，仔细研究 和 ，这两个基因在给予患者的相应抗乳腺癌药物的代谢和/或消除中起主要作用。它们代谢的基因变异可能与不同的代谢表型有关，这些表型可能由于毒性或亚治疗剂量而导致患者依从性降低。最后，这些知识有助于实现可能的个性化治疗方法，从而有可能改善乳腺癌患者的生存结果。
