Identification of minimal residual disease using the clonesight test for ultrasensitive ctDNA detection to anticipate late relapse in early breast cancer
Abstract Background Early-stage breast cancer (BC) diagnosis significantly reduces mortality, yet relapse remains a concern due to undetectable minimal residual disease (MRD). Liquid biopsies offer real-time insights into tumor dynamics, aiding MRD detection and therapy response evaluation. However,...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
|
| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13058-025-02016-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849314365050716160 |
|---|---|
| author | Iñaki Comino-Méndez Jesús Velasco-Suelto Javier Pascual Esperanza López-López Maria Elena Quirós-Ortega Celia Gaona-Romero Alejandro Martín-Muñoz Patricia Losana Yanira Heredia Emilio Alba Angel Guerrero-Zotano |
| author_facet | Iñaki Comino-Méndez Jesús Velasco-Suelto Javier Pascual Esperanza López-López Maria Elena Quirós-Ortega Celia Gaona-Romero Alejandro Martín-Muñoz Patricia Losana Yanira Heredia Emilio Alba Angel Guerrero-Zotano |
| author_sort | Iñaki Comino-Méndez |
| collection | DOAJ |
| description | Abstract Background Early-stage breast cancer (BC) diagnosis significantly reduces mortality, yet relapse remains a concern due to undetectable minimal residual disease (MRD). Liquid biopsies offer real-time insights into tumor dynamics, aiding MRD detection and therapy response evaluation. However, MRD detection is challenging due to low tumor DNA levels in circulation. Methods This prospective study included 20 HR + BC patients who had completed at least 5 years of adjuvant endocrine therapy (ET). Plasma samples were collected every 6 months over a median follow-up period of 2 years. Tumor-specific somatic variants identified through tumor tissue sequencing served as biomarkers for a patient-informed circulating tumor DNA (ctDNA) assay (CloneSight), which utilized a multiplex PCR-based next-generation sequencing (NGS) workflow. Results ctDNA was detected in patients who experienced clinical relapse, with positivity observed up to 68 months (5.7 years) prior to overt recurrence, highlighting its potential for early relapse identification. In non-relapsed patients, ctDNA remained undetectable in 93% of cases, reflecting a potential high level of specificity. The assay detected ctDNA in 50% of relapsed patients, while no ctDNA signal was identified in the majority of non-relapsed cases. Conclusion Our exploratory findings indicate that CloneSight could be a promising tool for MRD detection and relapse prediction, providing a cost-effective, patient-informed approach to ctDNA monitoring. The ability of this approach to detect relapse prior to clinical recurrence suggests its potential relevance in improving patient monitoring. These findings suggest that ctDNA-based MRD assays could play a role in future surveillance strategies for HR + BC, though further studies in larger cohorts are needed to confirm their clinical applicability. |
| format | Article |
| id | doaj-art-ced1e1029dde4ace8d9fddee67d4eb05 |
| institution | Kabale University |
| issn | 1465-542X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj-art-ced1e1029dde4ace8d9fddee67d4eb052025-08-20T03:52:28ZengBMCBreast Cancer Research1465-542X2025-05-0127111010.1186/s13058-025-02016-7Identification of minimal residual disease using the clonesight test for ultrasensitive ctDNA detection to anticipate late relapse in early breast cancerIñaki Comino-Méndez0Jesús Velasco-Suelto1Javier Pascual2Esperanza López-López3Maria Elena Quirós-Ortega4Celia Gaona-Romero5Alejandro Martín-Muñoz6Patricia Losana7Yanira Heredia8Emilio Alba9Angel Guerrero-Zotano10Medical Oncology Department, Hospital Universitario Virgen de la VictoriaMedical Oncology Department, Hospital Universitario Virgen de la VictoriaMedical Oncology Department, Hospital Universitario Virgen de la VictoriaMedical Oncology Department, Hospital Universitario Virgen de la VictoriaMedical Oncology Department, Hospital Universitario Virgen de la VictoriaMedical Oncology Department, Hospital Universitario Virgen de la VictoriaHematological Malignancies Clinical Research Unit, Centro Nacional de Investigaciones Oncologicas (CNIO)Altum Sequencing CoAltum Sequencing CoMedical Oncology Department, Hospital Universitario Virgen de la VictoriaMedical Oncology Department, Fundación Instituto Valenciano de OncologíaAbstract Background Early-stage breast cancer (BC) diagnosis significantly reduces mortality, yet relapse remains a concern due to undetectable minimal residual disease (MRD). Liquid biopsies offer real-time insights into tumor dynamics, aiding MRD detection and therapy response evaluation. However, MRD detection is challenging due to low tumor DNA levels in circulation. Methods This prospective study included 20 HR + BC patients who had completed at least 5 years of adjuvant endocrine therapy (ET). Plasma samples were collected every 6 months over a median follow-up period of 2 years. Tumor-specific somatic variants identified through tumor tissue sequencing served as biomarkers for a patient-informed circulating tumor DNA (ctDNA) assay (CloneSight), which utilized a multiplex PCR-based next-generation sequencing (NGS) workflow. Results ctDNA was detected in patients who experienced clinical relapse, with positivity observed up to 68 months (5.7 years) prior to overt recurrence, highlighting its potential for early relapse identification. In non-relapsed patients, ctDNA remained undetectable in 93% of cases, reflecting a potential high level of specificity. The assay detected ctDNA in 50% of relapsed patients, while no ctDNA signal was identified in the majority of non-relapsed cases. Conclusion Our exploratory findings indicate that CloneSight could be a promising tool for MRD detection and relapse prediction, providing a cost-effective, patient-informed approach to ctDNA monitoring. The ability of this approach to detect relapse prior to clinical recurrence suggests its potential relevance in improving patient monitoring. These findings suggest that ctDNA-based MRD assays could play a role in future surveillance strategies for HR + BC, though further studies in larger cohorts are needed to confirm their clinical applicability.https://doi.org/10.1186/s13058-025-02016-7Liquid biopsyEarly breast cancerCirculating tumor DNAMinimal residual disease |
| spellingShingle | Iñaki Comino-Méndez Jesús Velasco-Suelto Javier Pascual Esperanza López-López Maria Elena Quirós-Ortega Celia Gaona-Romero Alejandro Martín-Muñoz Patricia Losana Yanira Heredia Emilio Alba Angel Guerrero-Zotano Identification of minimal residual disease using the clonesight test for ultrasensitive ctDNA detection to anticipate late relapse in early breast cancer Breast Cancer Research Liquid biopsy Early breast cancer Circulating tumor DNA Minimal residual disease |
| title | Identification of minimal residual disease using the clonesight test for ultrasensitive ctDNA detection to anticipate late relapse in early breast cancer |
| title_full | Identification of minimal residual disease using the clonesight test for ultrasensitive ctDNA detection to anticipate late relapse in early breast cancer |
| title_fullStr | Identification of minimal residual disease using the clonesight test for ultrasensitive ctDNA detection to anticipate late relapse in early breast cancer |
| title_full_unstemmed | Identification of minimal residual disease using the clonesight test for ultrasensitive ctDNA detection to anticipate late relapse in early breast cancer |
| title_short | Identification of minimal residual disease using the clonesight test for ultrasensitive ctDNA detection to anticipate late relapse in early breast cancer |
| title_sort | identification of minimal residual disease using the clonesight test for ultrasensitive ctdna detection to anticipate late relapse in early breast cancer |
| topic | Liquid biopsy Early breast cancer Circulating tumor DNA Minimal residual disease |
| url | https://doi.org/10.1186/s13058-025-02016-7 |
| work_keys_str_mv | AT inakicominomendez identificationofminimalresidualdiseaseusingtheclonesighttestforultrasensitivectdnadetectiontoanticipatelaterelapseinearlybreastcancer AT jesusvelascosuelto identificationofminimalresidualdiseaseusingtheclonesighttestforultrasensitivectdnadetectiontoanticipatelaterelapseinearlybreastcancer AT javierpascual identificationofminimalresidualdiseaseusingtheclonesighttestforultrasensitivectdnadetectiontoanticipatelaterelapseinearlybreastcancer AT esperanzalopezlopez identificationofminimalresidualdiseaseusingtheclonesighttestforultrasensitivectdnadetectiontoanticipatelaterelapseinearlybreastcancer AT mariaelenaquirosortega identificationofminimalresidualdiseaseusingtheclonesighttestforultrasensitivectdnadetectiontoanticipatelaterelapseinearlybreastcancer AT celiagaonaromero identificationofminimalresidualdiseaseusingtheclonesighttestforultrasensitivectdnadetectiontoanticipatelaterelapseinearlybreastcancer AT alejandromartinmunoz identificationofminimalresidualdiseaseusingtheclonesighttestforultrasensitivectdnadetectiontoanticipatelaterelapseinearlybreastcancer AT patricialosana identificationofminimalresidualdiseaseusingtheclonesighttestforultrasensitivectdnadetectiontoanticipatelaterelapseinearlybreastcancer AT yaniraheredia identificationofminimalresidualdiseaseusingtheclonesighttestforultrasensitivectdnadetectiontoanticipatelaterelapseinearlybreastcancer AT emilioalba identificationofminimalresidualdiseaseusingtheclonesighttestforultrasensitivectdnadetectiontoanticipatelaterelapseinearlybreastcancer AT angelguerrerozotano identificationofminimalresidualdiseaseusingtheclonesighttestforultrasensitivectdnadetectiontoanticipatelaterelapseinearlybreastcancer |