Ru Wang , Bin Wang , Huimin Zhang , Xiaoqin Liao , Bohui Shi , Yuhui Zhou , Can Zhou , Yu Yan , Wei Zhang , Ke Wang , Guanqun Ge , Yu Ren , Xiaojiang Tang , Baoyu Gan , Jianjun He , Ligang Niu
{"title":"将循环肿瘤 DNA 作为乳腺癌患者原发性全身治疗期间疗效和预后的标记物进行早期评估","authors":"Ru Wang , Bin Wang , Huimin Zhang , Xiaoqin Liao , Bohui Shi , Yuhui Zhou , Can Zhou , Yu Yan , Wei Zhang , Ke Wang , Guanqun Ge , Yu Ren , Xiaojiang Tang , Baoyu Gan , Jianjun He , Ligang Niu","doi":"10.1016/j.breast.2024.103738","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>We assessed the potential role of serial circulating tumor DNA (ctDNA) as a biomarker to monitor treatment response to primary systemic therapy (PST) in breast cancer and evaluated the predictive value of ctDNA to further identify patients with residual disease.</p></div><div><h3>Methods</h3><p>We prospectively enrolled 208 plasma samples collected at three time points (before PST, after 2 cycles of treatment, before surgery) of 72 patients with stage Ⅱ-III breast cancer. Somatic mutations in plasma samples were identified using a customized 128-gene capture panel with next-generation sequencing. The correlation between early change in ctDNA levels and treatment response or long-term clinical outcomes was assessed.</p></div><div><h3>Results</h3><p>37 of 72 (51.4%) patients harbored detectable ctDNA alterations at baseline. Patients with complete response showed a larger decrease in ctDNA levels during PST. The median relative change of variant allele fraction (VAF) was −97.4%, −46.7%, and +21.1% for patients who subsequently had a complete response (n = 11), partial response (n = 11), and no response (n = 15) (<em>p</em> = 0.0012), respectively. In addition, the relative change of VAF between the pretreatment and first on-treatment blood draw exhibited the optimal predictive value to tumor response after PST (area under the curve, AUC = 0.7448, <em>p</em> = 0.02). More importantly, early change of ctDNA levels during treatment have significant prognostic value for patients with BC, there was a significant correlation between early decrease of VAF and longer recurrence-free survival compared to those with an VAF increase (HR = 12.54; 95% CI, 2.084 to 75.42, <em>p</em> = 0.0063).</p></div><div><h3>Conclusion</h3><p>Early changes of ctDNA are strongly correlated with therapeutic efficacy to PST and clinical outcomes in BC patients. The integration of preoperative ctDNA evaluation could help improving the perioperative management for BC patients receiving PST.</p></div>","PeriodicalId":9093,"journal":{"name":"Breast","volume":"76 ","pages":"Article 103738"},"PeriodicalIF":5.7000,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0960977624000699/pdfft?md5=139144f8d2493f0f902f2d4d26d9b111&pid=1-s2.0-S0960977624000699-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Early evaluation of circulating tumor DNA as marker of therapeutic efficacy and prognosis in breast cancer patients during primary systemic therapy\",\"authors\":\"Ru Wang , Bin Wang , Huimin Zhang , Xiaoqin Liao , Bohui Shi , Yuhui Zhou , Can Zhou , Yu Yan , Wei Zhang , Ke Wang , Guanqun Ge , Yu Ren , Xiaojiang Tang , Baoyu Gan , Jianjun He , Ligang Niu\",\"doi\":\"10.1016/j.breast.2024.103738\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>We assessed the potential role of serial circulating tumor DNA (ctDNA) as a biomarker to monitor treatment response to primary systemic therapy (PST) in breast cancer and evaluated the predictive value of ctDNA to further identify patients with residual disease.</p></div><div><h3>Methods</h3><p>We prospectively enrolled 208 plasma samples collected at three time points (before PST, after 2 cycles of treatment, before surgery) of 72 patients with stage Ⅱ-III breast cancer. Somatic mutations in plasma samples were identified using a customized 128-gene capture panel with next-generation sequencing. The correlation between early change in ctDNA levels and treatment response or long-term clinical outcomes was assessed.</p></div><div><h3>Results</h3><p>37 of 72 (51.4%) patients harbored detectable ctDNA alterations at baseline. Patients with complete response showed a larger decrease in ctDNA levels during PST. The median relative change of variant allele fraction (VAF) was −97.4%, −46.7%, and +21.1% for patients who subsequently had a complete response (n = 11), partial response (n = 11), and no response (n = 15) (<em>p</em> = 0.0012), respectively. In addition, the relative change of VAF between the pretreatment and first on-treatment blood draw exhibited the optimal predictive value to tumor response after PST (area under the curve, AUC = 0.7448, <em>p</em> = 0.02). More importantly, early change of ctDNA levels during treatment have significant prognostic value for patients with BC, there was a significant correlation between early decrease of VAF and longer recurrence-free survival compared to those with an VAF increase (HR = 12.54; 95% CI, 2.084 to 75.42, <em>p</em> = 0.0063).</p></div><div><h3>Conclusion</h3><p>Early changes of ctDNA are strongly correlated with therapeutic efficacy to PST and clinical outcomes in BC patients. 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Early evaluation of circulating tumor DNA as marker of therapeutic efficacy and prognosis in breast cancer patients during primary systemic therapy
Background
We assessed the potential role of serial circulating tumor DNA (ctDNA) as a biomarker to monitor treatment response to primary systemic therapy (PST) in breast cancer and evaluated the predictive value of ctDNA to further identify patients with residual disease.
Methods
We prospectively enrolled 208 plasma samples collected at three time points (before PST, after 2 cycles of treatment, before surgery) of 72 patients with stage Ⅱ-III breast cancer. Somatic mutations in plasma samples were identified using a customized 128-gene capture panel with next-generation sequencing. The correlation between early change in ctDNA levels and treatment response or long-term clinical outcomes was assessed.
Results
37 of 72 (51.4%) patients harbored detectable ctDNA alterations at baseline. Patients with complete response showed a larger decrease in ctDNA levels during PST. The median relative change of variant allele fraction (VAF) was −97.4%, −46.7%, and +21.1% for patients who subsequently had a complete response (n = 11), partial response (n = 11), and no response (n = 15) (p = 0.0012), respectively. In addition, the relative change of VAF between the pretreatment and first on-treatment blood draw exhibited the optimal predictive value to tumor response after PST (area under the curve, AUC = 0.7448, p = 0.02). More importantly, early change of ctDNA levels during treatment have significant prognostic value for patients with BC, there was a significant correlation between early decrease of VAF and longer recurrence-free survival compared to those with an VAF increase (HR = 12.54; 95% CI, 2.084 to 75.42, p = 0.0063).
Conclusion
Early changes of ctDNA are strongly correlated with therapeutic efficacy to PST and clinical outcomes in BC patients. The integration of preoperative ctDNA evaluation could help improving the perioperative management for BC patients receiving PST.
期刊介绍：
The Breast is an international, multidisciplinary journal for researchers and clinicians, which focuses on translational and clinical research for the advancement of breast cancer prevention, diagnosis and treatment of all stages.
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