by Binliang Liu, Zheyu Hu, Jialu Ran, Ning Xie, Can Tian, Yu
Tang, Quchang Ouyang
The Breast: Published: July 19, 2022
Purpose
Circulating tumor DNA (ctDNA) has good clinical guiding
value for metastatic breast cancer (MBC) patients. This study aimed to apply a
novel genetic analysis approach for therapeutic prediction based on ctDNA
alterations.
Method
This nonrandomized, multicenter study recruited 223 MBC
patients (NCT05079074). Plasma samples were collected for target-capture deep
sequencing of ctDNA at baseline, after the 2nd cycle of treatment, and when
progressive disease (PD) was evaluated. Samples were categorized into four
levels according to the number of ctDNA alterations: level 1 (no alterations),
level 2 (1–2 alterations), level 3 (3–4 alterations) and level 4 (≥5
alterations). According to ctDNA alteration level and variant allele frequency
(VAF), a novel ctDNA-level Response Evaluation Criterion in Solid Tumors
(ctle-RECIST) was established to assess treatment response and predict progression-free
survival (PFS).
Results
The median PFS in level 1 (6.63 months) patients was
significantly longer than that in level 2–4 patients (level 2: 5.70 months;
level 3–4: 4.90 months, p < 0.05). After 2 cycles of treatment,
based on ctle-RECIST, the median PFS of level-based disease control rate
(lev-DCR) patients was significantly longer than that of level-based PD
(lev-PD) patients [HR 2.42 (1.52–3.85), p < 0.001]. In addition,
we found that ctDNA level assessment could be a good supplement to radiologic
assessment. The median PFS in the dual-DCR group tended to be longer than that
in the single-DCR group [HR 1.41 (0.93–2.13), p = 0.107].
Conclusion
The ctDNA alteration level and ctle-RECIST could be novel
biomarkers of prognosis and could complement radiologic assessment in MBC.
