Dataset Information

Longitudinal dynamics of circulating tumor DNA for treatment monitoring in patients with breast cancer recurrence.

ABSTRACT: The prevalence and dynamics of circulating tumor DNA (ctDNA) in patients with breast cancer recurrence or de novo metastatic cancer were examined in a retrospective analysis of a prospective observational cohort. Twenty-three recurrent/metastatic breast cancer cases (8 locoregional, 15 distant metastasis) were enrolled, and sequential plasma samples were obtained. Anchor mutations were selected from the target sequencing of each patient's primary and/or metastatic tumor. An in-house developed assay (UHS assay) was employed for a tumor-informed ctDNA assay during treatment and follow-up. A median of three (range 1-5) anchor mutations per case were applied for ctDNA detection. ctDNA was detected in 14 (63.6%, 14/22) cases at the time of enrollment and 18 (78.5%, 18/23) cases during follow-up. More anchor mutations and higher tumor burden were significantly related to higher ctDNA positive rates (p-value 0.036, 0.043, respectively). The mean enriched variant allele frequency (eVAF) at each time point was significantly higher for stable or progressive disease responses (ANOVA test p-value < 0.001). Eight patients showed an increase in their ctDNA eVAF prior to clinical progression with a mean lead time of 6.2 months (range 1.5-11 months). ctDNA dynamics measured using personalized assay reflected the clinical course of breast cancer recurrence.

SUBMITTER: Yoo TR

PROVIDER: S-EPMC11364657 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Longitudinal dynamics of circulating tumor DNA for treatment monitoring in patients with breast cancer recurrence.

Yoo Tae-Kyung Robyn TR Lee Ji-Young JY Park Hwan H Cho Whi-Kyung WK Jeon Seyeon S Jun Ha Ra HR Lee Sae Byul SB Chung Il Yong IY Kim Hee Jeong HJ Ko Beom Seok BS Lee Jong Won JW Son Byung Ho BH Ahn Sei-Hyun SH Jeong Jae Ho JH Kim Jeong Eun JE Ahn Jin-Hee JH Jung Kyung Hae KH Kim Sung-Bae SB Lee Hee Jin HJ Gong Gyungyub G Kim Jisun J Chun Sung-Min SM

Scientific reports 20240831 1

The prevalence and dynamics of circulating tumor DNA (ctDNA) in patients with breast cancer recurrence or de novo metastatic cancer were examined in a retrospective analysis of a prospective observational cohort. Twenty-three recurrent/metastatic breast cancer cases (8 locoregional, 15 distant metastasis) were enrolled, and sequential plasma samples were obtained. Anchor mutations were selected from the target sequencing of each patient's primary and/or metastatic tumor. An in-house developed as ...[more]

PMID: 39215119

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Project description:Uterine serous carcinoma (USC) and carcinosarcomas (CSs) are rare, highly aggressive variants of endometrial cancer. No reliable tumor biomarkers are currently available to guide response to treatment or detection of early recurrence in USC/CS patients. Circulating tumor DNA (ctDNA) identified using ultrasensitive technology such as droplet digital polymerase chain reaction (ddPCR) may represent a novel platform for the identification of occult disease. We explored the use of personalized ctDNA markers for monitoring USC and CS patients. Tumor and plasma samples from USC/CS patients were collected at the time of surgery and/or during the treatment course for assessment of tumor-specific somatic structural variants (SSVs) by a clinical-grade next-generation sequencing (NGS) platform (i.e., Foundation Medicine) and a droplet digital PCR instrument (Raindance, ddPCR). The level of ctDNA was quantified by droplet digital PCR in plasma samples and correlated to clinical findings, including CA-125 serum and/or computed tomography (CT) scanning results. The genomic-profiling-based assay identified mutated "driver" target genes for ctDNA analysis in all USC/CS patients. In multiple patients, longitudinal ctDNA testing was able to detect the presence of cancer cells before the recurrent tumor was clinically detectable by either CA-125 or CT scanning. Persistent undetectable levels of ctDNA following initial treatment were associated with prolonged progression-free and overall survival. In a USC patient, CA-125 and TP53 mutations but not PIK3CA mutations become undetectable in the plasma at the time of recurrence, suggesting that more than one customized probe should be used for monitoring ctDNA. Longitudinal ctDNA testing using tumor-informed assays may identify the presence of residual tumors, predict responses to treatment, and identify early recurrences in USC/CS patients. Recognition of disease persistence and/or recurrence through ctDNA surveillance may allow earlier treatment of recurrent disease and has the potential to change clinical practice in the management of USC and CS patients. CtDNA validation studies in USC/CS patients prospectively enrolled in treatment trials are warranted.

Project description:BackgroundThe incorporation of circulating tumor DNA (ctDNA) into the management of operable breast cancer (BC) has been hampered by the heterogeneous results from different studies. We aimed to assess the prognostic value of ctDNA in patients with operable (non metastatic) BC.Materials and methodsA systematic search of databases (PubMed/Medline, Embase, and CENTRAL) and conference proceedings was conducted to identify studies reporting the association of ctDNA detection with disease-free survival (DFS) and overall survival (OS) in patients with stage I-III BC. Log-hazard ratios (HRs) were pooled at each timepoint of ctDNA assessment (baseline, after neoadjuvant therapy, and follow-up). ctDNA assays were classified as primary tumor-informed and non tumor-informed.ResultsOf the 3174 records identified, 57 studies including 5779 patients were eligible. In univariate analyses, ctDNA detection was associated with worse DFS at baseline [HR 2.98, 95% confidence interval (CI) 1.92-4.63], after neoadjuvant therapy (HR 7.69, 95% CI 4.83-12.24), and during follow-up (HR 14.04, 95% CI 7.55-26.11). Similarly, ctDNA detection at all timepoints was associated with worse OS (at baseline: HR 2.76, 95% CI 1.60-4.77; after neoadjuvant therapy: HR 2.72, 95% CI 1.44-5.14; and during follow-up: HR 9.19, 95% CI 3.26-25.90). Similar DFS and OS results were observed in multivariate analyses. Pooled HRs were numerically higher when ctDNA was detected at the end of neoadjuvant therapy or during follow-up and for primary tumor-informed assays. ctDNA detection sensitivity and specificity for BC recurrence ranged from 0.31 to 1.0 and 0.7 to 1.0, respectively. The mean lead time from ctDNA detection to overt recurrence was 10.81 months (range 0-58.9 months).ConclusionsctDNA detection was associated with worse DFS and OS in patients with operable BC, particularly when detected after treatment and using primary tumor-informed assays. ctDNA detection has a high specificity for anticipating BC relapse.

Dataset Information

Longitudinal dynamics of circulating tumor DNA for treatment monitoring in patients with breast cancer recurrence.

Publications

Longitudinal dynamics of circulating tumor DNA for treatment monitoring in patients with breast cancer recurrence.

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