Potential Impact of Preoperative Circulating Biomarkers on Individual Escalating/de-Escalating Strategies in Early Breast Cancer

Gianni, Caterina; Palleschi, Michela; Merloni, Filippo; Bleve, Sara; Casadei, Chiara; Sirico, Marianna; Menna, Grazia; Sarti, Samanta; Cecconetto, Lorenzo; Mariotti, Marita; Giorgi, Ugo De

doi:10.3390/cancers15010096

Cited by 4 publications

(3 citation statements)

References 189 publications

(230 reference statements)

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“…The prognostic value of ctDNA before curative treatment remains controversial in various cancer types [17][18][19][20]. We then examined whether the pre-operative ctDNA status can identify patients at a higher risk of recurrence.…”

Section: Pre-operative Ctdna Positivity Detected By Fixed Assays and ...mentioning

confidence: 99%

Evaluation of Molecular Residual Disease by a Fixed Panel in Resectable Colorectal Cancer

Yang,

Yu,

et al. 2024

Cancer Res Treat

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Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumorinformed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods75 patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and pre-operative and post-operative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. ResultsThe tumor-informed fixed assay had a higher pre-operative positive rate than the tumoragnostic assay (73.3% vs 57.3%). The pre-op ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined post-op ctDNA positivity was significantly associated with worse DFS (HR, 20.74, p<0.001), which was an independent predictor by multivariable analysis (HR, 28.57, 95%CI 7.10−114.9; p<0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest pre-operative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in post-op landmark (HR, 26.34, 95%CI, p<0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04, 95%CI, p=0.052). ConclusionOur study confirmed the prognostic value of the ctDNA positivity at post-op day 7 by the tumor-

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Section: Pre-operative Ctdna Positivity Detected By Fixed Assays and ...mentioning

confidence: 99%

Evaluation of Molecular Residual Disease by a Fixed Panel in Resectable Colorectal Cancer

Yang,

Yu,

et al. 2024

Cancer Res Treat

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“…Initially, the presence of ccfDNA in human plasma was a curious observation with unclear implications. It wasn't until recent decades, however, that technological advancements in genomic sequencing and molecular diagnostics brought ccfDNA to the forefront of medical research [10]. These advancements have allowed for the precise quantification and characterization of ccfDNA, revealing its potential as a biomarker for various diseases [11].…”

Section: Historical Perspective and Evolution In Diagnosticsmentioning

confidence: 99%

Exploring the Role of Circulating Cell-Free DNA in Disease Diagnosis and Therapy

Odah

2024

Preprint

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Recent advancements in molecular diagnostics have highlighted the potential of circulating cell-free DNA (ccfDNA) as a biomarker in various diseases. This study aims to explore the role of ccfDNA in the early diagnosis, prognosis, and therapeutic monitoring of diseases, with a focus on oncology. We conducted a comprehensive review and analysis of current literature, combined with experimental approaches involving advanced genomic sequencing and bioinformatics techniques. Our research systematically characterizes the molecular composition of ccfDNA, including its origins, size distribution, and methylation patterns, across different disease states. Furthermore, we investigate the dynamics of ccfDNA release and clearance in the bloodstream, elucidating mechanisms that could influence its diagnostic accuracy. In the context of cancer, we analyze the correlation between tumor-derived ccfDNA and disease progression, response to therapy, and overall survival. Our findings indicate that ccfDNA holds promise as a non-invasive biomarker for early disease detection, real-time monitoring of treatment efficacy, and potentially, predicting relapse. This study contributes to the growing field of liquid biopsies and opens new avenues for personalized medicine, emphasizing the need for standardized protocols in ccfDNA analysis to maximize its clinical utility. The implications of our findings extend beyond oncology, suggesting potential applications of ccfDNA in other pathological conditions.

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“…Despite most patients are diagnosed with early BC, up to 30% of these cases will relapse in the first 10 years of follow-up. Since current prognostic models for relapse and survival are imperfect, leading to adjuvant or neoadjuvant overtreatment of many patients [ 9 ], the identification of other prognostic factors is necessary to safely escalate or descalate adjuvant and neoadjuvant treatment [ 10 ]. The role of the immune response in BC has not been fully elucidated, but the recent introduction of immunotherapy both in early and advanced BC [ 11 ] together with a better understanding of the contribution of immune microenvironment to chemotherapy and targeted treatment response has fostered the search for new immune response-related biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Deconstructing neutrophil to lymphocyte ratio (NLR) in early breast cancer: lack of prognostic utility and biological correlates across tumor subtypes

Garcia-Torralba,

Pérez Ramos,

Ivars Rubio

et al. 2024

Breast Cancer Res Treat

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Purpose The prognostic utility and biological correlates of neutrophil to lymphocyte ratio (NLR), a potential biomarker of the balance between immune response and the inflammatory status, are still uncertain in breast cancer (BC). Methods We analysed a cohort of 959 women with early breast cancer, mostly treated with neoadjuvant or adjuvant chemotherapy. Clinical and pathological data, survival, NLR (continuous and categorical) and stromal tumor infiltrating lymphocytes (sTIL) were evaluated. Results NLR was only weakly associated with Ki67, while no association was found for grade, histology, immunohistochemical subtype or stage. Lymphocyte infiltration of the tumor did not correlate with NLR (Rho: 0.05, p = 0.30). These results were similar in the whole group and across the different BC subtypes, with no differences in triple negative BC. Relapse free interval (RFI), breast cancer specific survival (BCSS) and overall survival (OS) changed according to pre-treatment NLR neither in the univariate nor in the multivariate Cox models (RFI: HR 0.948, p = 0.61; BCSS: HR 0.920, p = 0.57; OS: HR 0.96, p = 0.59). Conclusion These results question the utility of NLR as a prognostic biomarker in early breast cancer and suggest the lack of correlation of NLR with tumor microenvironment immune response.

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Potential Impact of Preoperative Circulating Biomarkers on Individual Escalating/de-Escalating Strategies in Early Breast Cancer

Cited by 4 publications

References 189 publications

Evaluation of Molecular Residual Disease by a Fixed Panel in Resectable Colorectal Cancer

Evaluation of Molecular Residual Disease by a Fixed Panel in Resectable Colorectal Cancer

Exploring the Role of Circulating Cell-Free DNA in Disease Diagnosis and Therapy

Deconstructing neutrophil to lymphocyte ratio (NLR) in early breast cancer: lack of prognostic utility and biological correlates across tumor subtypes

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