Aguilar-Mahecha Adriana, Lafleur Josiane, Brousse Susie, Savichtcheva Olga, Holden Kimberly A, Faulkner Nathan, McLennan Graham, Jensen Taylor J, Basik Mark
Lady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
Laboratory Corporation of America, Burlington, NC 27216-2240, USA.
Cancers (Basel). 2021 Mar 16;13(6):1331. doi: 10.3390/cancers13061331.
Circulating tumor DNA (ctDNA) offers high sensitivity and specificity in metastatic cancer. However, many ctDNA assays rely on specific mutations in recurrent genes or require the sequencing of tumor tissue, difficult to do in a metastatic disease. The purpose of this study was to define the predictive and prognostic values of the whole-genome sequencing (WGS) of ctDNA in metastatic breast cancer (MBC).
Plasma from 25 patients with MBC were taken at the baseline, prior to treatment (T0), one week (T1) and two weeks (T2) after treatment initiation and subjected to low-pass WGS. DNA copy number changes were used to calculate a Genomic Instability Number (GIN). A minimum predefined GIN value of 170 indicated detectable ctDNA. GIN values were correlated with the treatment response at three and six months by Response Evaluation Criteria in Solid Tumours assessed by imaging (RECIST) criteria and with overall survival (OS).
GIN values were detectable (>170) in 64% of patients at the baseline and were significantly prognostic (41 vs. 18 months OS for nondetectable vs. detectable GIN). Detectable GIN values at T1 and T2 were significantly associated with poor OS. Declines in GIN at T1 and T2 of > 50% compared to the baseline were associated with three-month response and, in the case of T1, with OS. On the other hand, a rise in GIN at T2 was associated with a poor response at three months.
Very early measurements using WGS of cell-free DNA (cfDNA) from the plasma of MBC patients provided a tumor biopsy-free approach to ctDNA measurement that was both predictive of the early tumor response at three months and prognostic.
循环肿瘤DNA（ctDNA）在转移性癌症中具有高敏感性和特异性。然而，许多ctDNA检测依赖于复发基因中的特定突变或需要对肿瘤组织进行测序，而这在转移性疾病中很难做到。本研究的目的是确定ctDNA全基因组测序（WGS）在转移性乳腺癌（MBC）中的预测和预后价值。
收集25例MBC患者在基线、治疗前（T0）、治疗开始后1周（T1）和2周（T2）的血浆，并进行低深度WGS。DNA拷贝数变化用于计算基因组不稳定性数值（GIN）。预定义的最小GIN值为170表示可检测到ctDNA。通过影像学评估实体瘤疗效评价标准（RECIST）评估GIN值与3个月和6个月时的治疗反应以及总生存期（OS）的相关性。
64%的患者在基线时可检测到GIN值（>170），且具有显著的预后意义（不可检测与可检测GIN的OS分别为41个月和18个月）。T1和T2时可检测到的GIN值与较差的OS显著相关。与基线相比，T1和T2时GIN下降>50%与3个月时的反应相关，T1时还与OS相关。另一方面，T2时GIN升高与3个月时反应较差相关。
使用WGS对MBC患者血浆中的游离DNA（cfDNA）进行非常早期的检测，提供了一种无需肿瘤活检的ctDNA检测方法，该方法既能预测3个月时的早期肿瘤反应，又具有预后价值。
