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oai:recercat.cat:11351/95962024-12-13T10:20:45Zcom_2072_378070com_2072_378040col_2072_378092

Clearance of ctDNA in triple-negative and HER2-positive breast cancer patients during neoadjuvant treatment is correlated with pathologic complete response Ciriaco, Nikaoly Zamora, Esther Escriva de Romani, Santiago Miranda Gomez, Ignacio Saura, Cristina Ramon y Cajal, Santiago Espinosa-Bravo, Martin Peg, Vicente Jimenez, Jose Institut Català de la Salut [Ciriaco N] Pathology Department, Hospital del Mar, Barcelona, Spain. Universidad Autónoma de Barcelona, Barcelona, Spain. [Zamora E] Universitat Autònoma de Barcelona, Bellaterra, Spain. Breast Cancer Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Escrivá-de-Romaní S] Breast Cancer Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Miranda Gómez I] Servei de Radiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Jiménez Flores J] Molecular Oncology Lab. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Saura C] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Ramón Y Cajal S, Peg V] Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei d’Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Madrid, Spain. [Espinosa-Bravo M] Unitat de Patologia Mamària, Vall d’Hebron Hospital Universitari, Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus Mama - Càncer - Tractament Mama - Càncer - Aspectes genètics Marcadors tumorals DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms Other subheadings::Other subheadings::Other subheadings::/drug therapy CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::Cell-Free Nucleic Acids::Circulating Tumor DNA Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::tratamiento neoadyuvante COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::ácidos nucleicos::ácidos nucleicos libres de células::ADN tumoral circulante ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama Breast cancer; Liquid biopsy; Neoadjuvant therapy Càncer de mama; Biòpsia líquida; Teràpia neoadjuvant Cáncer de mama; Biopsia líquida; Terapia neoadyuvante Background: Although the standard of care is to perform surgery of primary breast cancer (BC) after neoadjuvant chemotherapy (NAC), for certain patients achieving clinical complete response (cCR) and pathologic complete response (pCR), omission of surgical treatment may be an option. Levels of circulating tumor DNA (ctDNA) during and after therapy could identify patients achieving minimal residual disease. In this study, we evaluated whether ctDNA clearance during NAC could be a correlate to effective response in human epidermal growth factor receptor 2 positive (HER2+) and triple-negative (TN) BC patients. Methods: A prospective study was conducted to identify patient-specific PIK3CA and TP53 mutations in tissue using next-generation sequencing, which could then be used to track the presence/absence of mutations prior to, during, and following NAC using Sysmex SafeSEQ technology. All patients underwent a surgical excision after NAC, and pCR was assessed. Results: A total of 29 TN and HER2+ BC patients were examined and 20 that carried mutations in the PIK3CA and/or TP53 genes were recruited. Overall, 19 of these 20 patients harbored at least one tumor-specific mutation in their plasma at baseline. After NAC, 15 patients (75.0%) achieved pCR according to the histopathologic evaluation of the surgical specimen, and 15 patients (75.0%) had a cCR; 18 of 20 patients (90.0%) had concordant pCR and cCR. The status of ‘no mutation detected’ (NMD) following NAC in cCR patients correctly identified the pCR in 14 of 15 patients (93.33%), as well as correctly ruled out pCR in three patients, with an accuracy of 89.47%. During the 12-month follow-up after surgery, 40 plasma samples collected from 15 patients all showed no detectable ctDNA (NMD), and no patient recurred. Conclusion: These findings prompt further research of the value of ctDNA for non-invasive prediction of clinical/pathological response, raising the possibility of sparing surgery following NAC in selected BC patients. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by a grant from Sysmex Inostics, Inc. The sponsor coordinated data collection from study centers, and funded the statistical analysis and medical writing assistance. 2023-05-23T10:15:43Z 2023-05-23T10:15:43Z 2022 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Ciriaco N, Zamora E, Escrivá-de-Romaní S, Miranda Gómez I, Jiménez Flores J, Saura C, et al. Clearance of ctDNA in triple-negative and HER2-positive breast cancer patients during neoadjuvant treatment is correlated with pathologic complete response. Ther Adv Med Oncol. 2022;14:1–12. 1758-8359 https://hdl.handle.net/11351/9596 10.1177/17588359221139601 36479470 000928023700001 http://hdl.handle.net/11351/9596 eng Therapeutic Advances in Medical Oncology;14 https://doi.org/10.1177/17588359221139601 Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess application/pdf SAGE Publications Scientia