Bernard Philip S, Wooderchak-Donahue Whitney, Wei Mei, Bray Steven M, Wood Kevin C, Parikh Baiju, McMillin Gwendolyn A
ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT 84108, USA.
Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA.
Cancers (Basel). 2021 Mar 11;13(6):1219. doi: 10.3390/cancers13061219.
Patients with breast cancer often receive many drugs to manage the cancer, side effects associated with cancer treatment, and co-morbidities (i.e., polypharmacy). Drug-drug and drug-gene interactions contribute to the risk of adverse events (AEs), which could lead to non-adherence and reduced efficacy. Here we investigated several well-characterized inherited (germline) pharmacogenetic (PGx) targets in 225 patients with breast cancer. All relevant clinical, pharmaceutical, and PGx diplotype data were aggregated into a single unifying informatics platform to enable an exploratory analysis of the cohort and to evaluate pharmacy ordering patterns. Of the drugs recorded, there were 38 for which high levels of evidence for clinical actionability with PGx was available from the US FDA and/or the Clinical Pharmacogenetics Implementation Consortium (CPIC). These data were associated with 10 pharmacogenes: and . All patients were taking at least one of the 38 drugs and had inherited at least one actionable PGx variant that would have informed prescribing decisions if this information had been available pre-emptively. The non-cancer drugs with PGx implications that were common (prescribed to at least one-third of patients) included anti-depressants, anti-infectives, non-steroidal anti-inflammatory drugs, opioids, and proton pump inhibitors. Based on these results, we conclude that pre-emptive PGx testing may benefit patients with breast cancer by informing drug and dose selection to maximize efficacy and minimize AEs.
乳腺癌患者通常会接受多种药物来治疗癌症、应对癌症治疗的副作用以及处理合并症（即多种药物联合使用）。药物与药物之间以及药物与基因之间的相互作用会增加不良事件（AE）的风险，这可能导致患者不依从治疗并降低疗效。在此，我们对225例乳腺癌患者中几个特征明确的遗传性（种系）药物遗传学（PGx）靶点进行了研究。所有相关的临床、药学和PGx双倍型数据都汇总到一个统一的信息学平台，以便对该队列进行探索性分析，并评估药房的用药模式。在记录的药物中，有38种药物可从美国食品药品监督管理局（FDA）和/或临床药物遗传学实施联盟（CPIC）获得关于PGx临床可操作性的高水平证据。这些数据与10个药物基因相关。所有患者都至少服用了38种药物中的一种，并且遗传了至少一种可操作的PGx变异体，如果这些信息能够提前获得，就可以为处方决策提供参考。具有PGx意义的常见非癌症药物（至少三分之一的患者使用过）包括抗抑郁药、抗感染药、非甾体抗炎药、阿片类药物和质子泵抑制剂。基于这些结果，我们得出结论，预防性PGx检测可能通过为药物和剂量选择提供参考，使疗效最大化并将不良事件最小化，从而使乳腺癌患者受益。
