Circulating Tumor DNA as a Predictive Marker of Recurrence for Patients With Stage II-III Breast Cancer Treated With Neoadjuvant Therapy

Lin, Po-Han; Wang, Mingyang; Lo, Chiao; Tsai, Li-Wei; Yen, Tzu-Chun; Huang, Thomas; Huang, Wei‐Chih; Yang, Kaiyong; Chen, Chih-Kai; Fan, Sheng-Chih; Kuo, Sung‐Hsin

doi:10.3389/fonc.2021.736769

Cited by 21 publications

(11 citation statements)

References 46 publications

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“…The pre‐operative ctDNA detection rate of our K‐Track ® assay for all patients was 44.3%, similar to [ 34 ]; the rate in combined high‐risk groups was 59.6%, slightly lower than 63% [ 35 ] and 78% [ 6 ] detection rates in their respective high‐risk cohorts. These studies all used a much more extensive sequencing approach than K‐Track ® and the non‐inferiority of our result again supported both clinical and economic values of the assay.…”

Section: Discussionsupporting

confidence: 69%

Genetic landscape and personalized tracking of tumor mutations in Vietnamese women with breast cancer

Hoang

Nguyen

et al. 2023

Molecular Oncology

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Breast cancer is the leading cause of cancer death in Vietnamese women, but its mutational landscape and actionable alterations for targeted therapies remain unknown. After treatment, a sensitive biomarker to complement conventional imaging to monitor patients is also lacking. In this prospective multi‐center study, 134 early‐stage breast cancer patients eligible for curative‐intent surgery were recruited. Genomic DNA from tumor tissues and paired white blood cells were sequenced to profile all tumor‐derived mutations in 95 cancer‐associated genes. Our bioinformatic algorithm was then utilized to identify top mutations for individual patients. Serial plasma samples were collected before surgery and at scheduled visits after surgery. Personalized assay tracking the selected mutations were performed to detect circulating tumor DNA (ctDNA) in the plasma. We found that the mutational landscape of the Vietnamese was largely similar to other Asian cohorts, showing higher TP53 mutation frequency than in Caucasians. Alterations in PIK3CA and PI3K signaling were dominant, particularly in our triple‐negative subgroup. Using top‐ranked mutations, we detected ctDNA in pre‐operative plasma in 24.6–43.5% of the hormone‐receptor‐positive groups and 76.9–80.8% of the hormone‐receptor‐negative groups. The detection rate was associated with breast cancer subtypes and clinicopathological features that increased the risk of relapse. Interim analysis after a 15‐month follow‐up revealed post‐operative detection of ctDNA in all three patients that had recurrence, with a lead time of 7–13 months ahead of clinical diagnosis. Our personalized assay is streamlined and affordable with promising clinical utility in residual cancer surveillance. We also generated the first somatic variant dataset for Vietnamese breast cancer women that could lay the foundation for precision cancer medicine in Vietnam.

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Section: Discussionsupporting

confidence: 69%

Genetic landscape and personalized tracking of tumor mutations in Vietnamese women with breast cancer

Hoang

Nguyen

et al. 2023

Molecular Oncology

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“…In TNBC, numerous reports have indicated that ctDNA fraction is an important biomarker for chemotherapy response and tumor progression. It is well known that a high level of ctDNA after neoadjuvant chemotherapy (NAC) is associated with shorter progression-free survival and relapse-free survival [ 38 , 39 , 40 , 41 , 42 , 43 , 48 , 49 ]. Similarly, a concentration of circulating cell-free DNA above 264 ng/mL is a strong marker of increased risk of relapse [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…Lin et al have achieved similar results on plasma samples from 95 breast cancer patients (among which 25 TNBC). In this report, the mutation and copy number state of a gene panel (TP53, PI3KCA, HER2, GATA3, CDH1, PTEN, AKT1, ESR1, S100A7-9, ZNF703, B2M, CCND1, c-MYC) were analyzed pre- and post-neoadjuvant chemotherapy (NAC) [ 48 ]. Li et al used a personalized QIAseq Targeted DNA Panel to amplify the coding region of chosen genes.…”

Section: Liquid Biopsy and Circulating Cell-free Nucleic Acids In Tnbcmentioning

confidence: 99%

“…They found that the post-NAC detection of alterations in selected genes is associated with worse relapse-free survival. Among these patients, HER2+ cases have displayed a longer relapse-free survival than regards the TNBC ones, probably due to the efficiencies of maintenance anti-HER2 antibody therapy [ 48 ]. The importance of specific ctDNA alterations in TNBC progression is further highlighted by Cavallone et al They analyzed tumor and serial blood samples from 26 TNBC patients collected before, during, and after NAC treatment by developing individual digital droplet PCR assays for 121 variants (average of five variants for a patient) previously identified from tumor genomic profiling through whole exome sequencing (WES) [ 49 ].…”

Section: Liquid Biopsy and Circulating Cell-free Nucleic Acids In Tnbcmentioning

confidence: 99%

“…Bioinformatical analysis has revealed 431 somatic breast cancer-related variants shared in both fluids. Among these, the most common pathogenic and probable pathogenic mutations are NF1, CHEK2, KMT2C, and PTEN, which are tumor suppressor genes commonly implicated in TNBC onset and progression [ 43 , 44 , 45 , 46 , 47 , 48 , 57 ]. These results proved that both plasma and urine-derived ctDNA from TNBC patients could be efficiently analyzed using a targeted sequencing approach.…”

Section: Liquid Biopsy and Circulating Cell-free Nucleic Acids In Tnbcmentioning

confidence: 99%

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An Overview of Circulating Cell-Free Nucleic Acids in Diagnosis and Prognosis of Triple-Negative Breast Cancer

Tierno

Grassi

Zanconati

et al. 2023

IJMS

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Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer due to its molecular heterogeneity and poor clinical outcomes. Analysis of circulating cell-free tumor nucleic acids (ctNAs) can improve our understanding of TNBC and provide efficient and non-invasive clinical biomarkers that may be representative of tumor heterogeneity. In this review, we summarize the potential of ctNAs to aid TNBC diagnosis and prognosis. For example, tumor fraction of circulating cell-free DNA (TFx) may be useful for molecular prognosis of TNBC: high TFx levels after neoadjuvant chemotherapy have been associated with shorter progression-free survival and relapse-free survival. Mutations and copy number variations of TP53 and PIK3CA/AKT genes in plasma may be important markers of TNBC onset, progression, metastasis, and for clinical follow-up. In contrast, the expression profile of circulating cell-free tumor non-coding RNAs (ctncRNAs) can be predictive of molecular subtypes of breast cancer and thus aid in the identification of TBNC. Finally, dysregulation of some circulating cell-free tumor miRNAs (miR17, miR19a, miR19b, miR25, miR93, miR105, miR199a) may have a predictive value for chemotherapy resistance. In conclusion, a growing number of efforts are highlighting the potential of ctNAs for future clinical applications in the diagnosis, prognosis, and follow-up of TNBC.

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Association of ctDNA detection and recurrence assessment in patients with neoadjuvant treatment

Zhou,

Mo,

et al. 2023

Cancer Medicine

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BackgroundThe utilization of neoadjuvant therapy is progressively expanding in various clinical settings. However, the absence of a clinically validated biomarker to evaluate the treatment response remains a significant challenge in the field. Circulating tumor DNA (ctDNA) detection, a novel and emerging monitoring approach in the field of oncology, holds promise as a potential prognostic biomarker for patients with cancer. This meta‐analysis investigated the clinical significance of ctDNA detection as a predictive tool for cancer recurrence in patients receiving neoadjuvant treatment.MethodsA comprehensive systematic literature search was conducted using public databases to identify relevant studies that investigated the association between ctDNA detection and cancer recurrence in patients receiving neoadjuvant treatment. Hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CI) were calculated to assess the relationship between cancer recurrence and relevant factors. Cancer recurrence was considered the primary outcome.ResultsA total of 23 studies encompassing 1590 patients across eight different cancer types were included in the final analysis. Positive ctDNA detection was significantly associated with higher cancer recurrence, especially at post‐neoadjuvant treatment and post‐surgery time points. The risk values for the different cancer categories and geographic areas also differed significantly.ConclusionOur comprehensive meta‐analysis revealed a significant positive correlation between ctDNA detection and a higher risk of cancer recurrence in patients receiving neoadjuvant treatment. In addition, the risk of recurrence was influenced by variations in cancer type, timing of detection, and geographic region. These findings highlight the promising clinical applicability of ctDNA as a prognostic marker and monitoring approach for patients with cancer. However, the precise mechanism is unknown and more evidence is needed for further research.

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Circulating Tumor DNA as a Predictive Marker of Recurrence for Patients With Stage II-III Breast Cancer Treated With Neoadjuvant Therapy

Cited by 21 publications

References 46 publications

Genetic landscape and personalized tracking of tumor mutations in Vietnamese women with breast cancer

Genetic landscape and personalized tracking of tumor mutations in Vietnamese women with breast cancer

An Overview of Circulating Cell-Free Nucleic Acids in Diagnosis and Prognosis of Triple-Negative Breast Cancer

Association of ctDNA detection and recurrence assessment in patients with neoadjuvant treatment

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