Early evaluation of circulating tumor DNA as marker of therapeutic efficacy and prognosis in breast cancer patients during primary systemic therapy

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

Early evaluation of circulating tumor DNA as marker of therapeutic efficacy and prognosis in breast cancer patients during primary systemic therapy

Breast. 2024 Apr 24:76:103738. doi: 10.1016/j.breast.2024.103738. Online ahead of print.

Authors

Ru Wang¹, Bin Wang¹, Huimin Zhang¹, Xiaoqin Liao¹, Bohui Shi¹, Yuhui Zhou¹, Can Zhou¹, Yu Yan¹, Wei Zhang¹, Ke Wang¹, Guanqun Ge¹, Yu Ren¹, Xiaojiang Tang¹, Baoyu Gan², Jianjun He³, Ligang Niu⁴

Affiliations

¹ Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
² Biobank of the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
³ Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China. Electronic address: chinahjj@163.com.
⁴ Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China. Electronic address: lgniu7704@163.com.

Abstract

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.

Keywords: Breast cancer; Primary systemic therapy; Treatment response; ctDNA; pCR.