Gemcitabine-carboplatin (GC) chemotherapy was efficacious in metastatic breast cancer (MBC) patients probably resistant to anthracyclines and taxanes, but showed significant interindividual variation in treatment responses. Early prediction of response to treatment is clinically relevant to identify patients who will achieve clinical benefit. In this study, nuclear magnetic resonance (NMR) based pharmacometabonomics was used to noninvasively predict the response to GC chemotherapy of 29 MBC patients with prior exposure to both anthracyclines and taxanes from a phase II study. Formate and acetate levels in the baseline serum collected prior to GC chemotherapy were identified as potential predictive markers to select patients who will achieve clinical benefit and to identify those who should not be treated with the therapy to avoid futile treatment. The significantly lower baseline levels of serum formate and acetate in patients with resistant disease may reflect the higher demand of them as alternate/additional nutritional sources to fuel the accelerated proliferation of breast cancer cells that are biologically more aggressive or resistant to therapy. The results suggest that pharmacometabonomics can be a potential useful tool for predicting chemotherapy response in the context of precision medicine. Prospective studies with larger patient cohorts are required for validation of the findings.

中文翻译：

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药物代谢组学分析显示转移性乳腺癌患者血清甲酸盐和乙酸盐与吉西他滨-卡铂化疗的不同应答相关

吉西他滨-卡铂（GC）化疗对可能对蒽环类和紫杉烷类耐药的转移性乳腺癌（MBC）患者有效，但在治疗反应中存在明显的个体差异。对治疗反应的早期预测在临床上与确定将获得临床益处的患者有关。在这项研究中，基于II期研究的基于核磁共振（NMR）的药物代谢组学被用于无创地预测29名先前接触过蒽环类和紫杉烷类的MBC患者对GC化疗的反应。GC化疗前收集的基线血清中的甲酸盐和乙酸盐水平被确定为潜在的预测指标，以选择可实现临床获益的患者，并确定那些不应接受治疗以避免徒劳治疗的患者。抗药性疾病患者血清甲酸酯和乙酸盐的基线水平显着降低，可能反映出它们作为替代/附加营养来源的需求更高，从而为生物学上更具攻击性或抗药性的乳腺癌细胞的加速增殖提供动力。结果表明，药物代谢组学可能是在精密医学领域中预测化疗反应的潜在有用工具。需要对更大的患者队列进行前瞻性研究，以验证发现。