The molecular tumor burden index as a response evaluation criterion in breast cancer

Zongbi Yi,Guohua Rong,Binghe Xu,Wenna Wang,Binliang Liu,Yanfang Guan,Jin Li,Xiuwen Guan,Fei Ma,Xiaoying Sun,Jiani Wang,Hongnan Mo,Haili Qian

doi:10.1038/s41392-021-00662-9

Abstract

Circulating tumor DNA (ctDNA) is a potential biomarker of prognosis and therapeutic response. We conducted this study to explore the role of the molecular tumor burden index (mTBI) in ctDNA as a therapeutic response and prognostic biomarker in a larger cohort prospective phase III randomized multicenter study. We collected 291 plasma samples from 125 metastatic breast cancer patients from the CAMELLIA study (NCT01917279). Target-capture deep sequencing of 1021 genes was performed to detect somatic variants in ctDNA from the plasma samples. The pretreatment mTBI value was correlated with tumor burden (P = 0.025). Patients with high-level pretreatment mTBI had shorter overall survival than patients with low-level pretreatment mTBI, and the median overall survival was 40.9 months and 68.4 months, respectively (P = 0.011). Patients with mTBI decrease to less than 0.02% at the first tumor evaluation had longer progression-free survival and overall survival (P < 0.001 and P = 0.007, respectively). The mTBI has good sensitivity to identify complete response/partial response and progressive disease based on computed tomography scans (88.5% and 87.5%, respectively). The patients classified as molecular responders had longer progression-free survival and overall survival than the nonmolecular responders in the overall cohort (P < 0.001 and P = 0.036, respectively), as well as in the cohort in which computed tomography scans were defined as representing stable disease (P = 0.027 and P = 0.015, respectively). The mTBI in ctDNA detected in liquid biopsies is a potential biomarker of therapeutic response and prognosis in patients with metastatic breast cancer.

Highlights

Despite the great advancements that have been made in solid tumor treatment, tumor metastasis remains the leading cause of cancerrelated death
Characteristics of patients and sample information A total of 125 patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer treated with first-line chemotherapy were included in this study
The other patient characteristics at baseline are summarized in Table 1. ctDNA analyses were performed for each patient at least once

Summary

Introduction

Despite the great advancements that have been made in solid tumor treatment, tumor metastasis remains the leading cause of cancerrelated death. Therapeutic monitoring is very important and can help choose the appropriate treatment for patients and avoid ineffective therapies and unnecessary side effects. Serial computed tomography (CT) imaging is generally used to monitor treatment response,[1] yet imaging examination does not fully represent the pathologic and molecular changes that occur during therapy. The long-term survival of patients with initial radiologically stable disease (SD) is not clear.[1] A blood biomarker with rapid kinetics could offer an earlier indication of treatment efficacy to help clarify therapeutic management decisions in such cases. It is crucial to find biomarkers that assess tumor burden with high specificity and sensitivity

Methods

Results

Conclusion