Ciccolini Joseph, Fanciullino Raphaelle, Serdjebi Cindy, Milano Gérard
SMARTc Pharmacokinetics Unit, UMR S_911 CRO2, AMU , Marseille , France.
Expert Opin Drug Metab Toxicol. 2015 May;11(5):719-29. doi: 10.1517/17425255.2015.1008447. Epub 2015 Feb 18.
Breast cancer has benefited from a number of innovative therapeutics over the last decade. Cytotoxics, hormone therapy, targeted therapies and biologics can now be given to ensure optimal management of patients. As life expectancy of breast cancer patients has been significantly stretched and that several lines of treatment are now made available, determining the best drug or drug combinations to be primarily given and the best dosing and scheduling for each patient is critical for ensuring an optimal toxicity/efficacy balance.
Defining patient's characteristics at the tumor level (pharmacogenomics) and the constitutional level (pharmacogenetics) is a rising trend in oncology. This review covers the latest strategies based upon the search of relevant biomarkers for efficacy, resistance and toxicity to be undertaken at the bedside to shift towards precision medicine in breast cancer patients.
In the expanding era of bioguided medicine, identifying relevant and clinically validated biomarkers from the plethora of published material remains an uneasy task. Sorting the variety of genetic and molecular markers that have been investigated over the last decade on their level of evidence and addressing the issue of drug exposure should help to improve the management of breast cancer therapy.
在过去十年中,乳腺癌受益于多种创新疗法。如今,细胞毒性药物、激素疗法、靶向疗法和生物制剂均可用于确保对患者进行最佳治疗。由于乳腺癌患者的预期寿命已显著延长,且现在有多种治疗方案可供选择,因此确定首先给予的最佳药物或药物组合以及针对每位患者的最佳给药剂量和方案对于确保最佳毒性/疗效平衡至关重要。
在肿瘤水平(药物基因组学)和体质水平(药物遗传学)定义患者特征是肿瘤学领域的一个新兴趋势。本综述涵盖了基于寻找相关生物标志物以评估疗效、耐药性和毒性的最新策略,这些策略将在床边进行,以推动乳腺癌患者向精准医学转变。
在生物导向医学不断发展的时代,从大量已发表的资料中识别相关且经过临床验证的生物标志物仍然是一项艰巨的任务。对过去十年研究的各种遗传和分子标志物按其证据水平进行分类,并解决药物暴露问题,应有助于改善乳腺癌治疗的管理。