53BP1 Accumulation in Circulating Tumor Cells Identifies Chemotherapy-Responsive Metastatic Breast Cancer Patients
Evidence suggests that the DNA end-binding protein p53-binding protein 1 (53BP1) is down-regulated in subsets of breast cancer. Circulating tumor cells (CTCs) provide accessible “biopsy material” to track cell traits and functions and their alterations during treatment. Here, we prospectively monito...
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doaj-4355791b2a414bf6954fdaf439b9e53e2020-11-25T02:44:06ZengMDPI AGCancers2072-66942020-04-011293093010.3390/cancers1204093053BP1 Accumulation in Circulating Tumor Cells Identifies Chemotherapy-Responsive Metastatic Breast Cancer PatientsFabienne Schochter0Kim Werner1Cäcilia Köstler2Anke Faul3Marie Tzschaschel4Barbara Alberter5Volkmar Müller6Hans Neubauer7Tanja Fehm8Thomas W.P. Friedl9Bernhard Polzer10Wolfgang Janni11Brigitte Rack12Lisa Wiesmüller13Department of Obstetrics and Gynecology, Ulm University, 89075 Ulm, GermanyDepartment of Obstetrics and Gynecology, Ulm University, 89075 Ulm, GermanyDivision of Personalized Tumor Therapy, Fraunhofer-Institute for Toxicology and Experimental Medicine, 93053 Regensburg, GermanyDepartment of Obstetrics and Gynecology, Ulm University, 89075 Ulm, GermanyDepartment of Obstetrics and Gynecology, Ulm University, 89075 Ulm, GermanyDivision of Personalized Tumor Therapy, Fraunhofer-Institute for Toxicology and Experimental Medicine, 93053 Regensburg, GermanyDepartment of Gynecology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyDepartment of Obstetrics and Gynecology, University of Duesseldorf, 40225 Duesseldorf, GermanyDepartment of Obstetrics and Gynecology, University of Duesseldorf, 40225 Duesseldorf, GermanyDepartment of Obstetrics and Gynecology, Ulm University, 89075 Ulm, GermanyDivision of Personalized Tumor Therapy, Fraunhofer-Institute for Toxicology and Experimental Medicine, 93053 Regensburg, GermanyDepartment of Obstetrics and Gynecology, Ulm University, 89075 Ulm, GermanyDepartment of Obstetrics and Gynecology, Ulm University, 89075 Ulm, GermanyDepartment of Obstetrics and Gynecology, Ulm University, 89075 Ulm, GermanyEvidence suggests that the DNA end-binding protein p53-binding protein 1 (53BP1) is down-regulated in subsets of breast cancer. Circulating tumor cells (CTCs) provide accessible “biopsy material” to track cell traits and functions and their alterations during treatment. Here, we prospectively monitored the 53BP1 status in CTCs from 67 metastatic breast cancer (MBC) patients with HER2- CTCs and known hormone receptor (HR) status of the primary tumor and/or metastases before, during, and at the end of chemotherapeutic treatment with Eribulin. Nuclear 53BP1 staining and genomic integrity were evaluated by immunocytochemical and whole-genome-amplification-based polymerase chain reaction (PCR) analysis, respectively. Comparative analysis of CTCs from patients with triple-negative and HR+ tumors revealed elevated 53BP1 levels in CTCs from patients with HR+ metastases, particularly following chemotherapeutic treatment. Differences in nuclear 53BP1 signals did not correlate with genomic integrity in CTCs at baseline or with nuclear γH2AX signals in MBC cell lines, indicating that 53BP1 detected features beyond DNA damage. Kaplan–Meier analysis revealed an increasing association between nuclear 53BP1-positivity and progression-free survival (PFS) during chemotherapy until the final visit. Our data suggest that 53BP1 detection in CTCs could be a useful marker to capture dynamic changes of chemotherapeutic responsiveness in triple-negative and HR+ MBC.https://www.mdpi.com/2072-6694/12/4/930metastatic breast cancercirculating tumor cellstriple-negativehormone receptorEribulinpredictive biomarker |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fabienne Schochter Kim Werner Cäcilia Köstler Anke Faul Marie Tzschaschel Barbara Alberter Volkmar Müller Hans Neubauer Tanja Fehm Thomas W.P. Friedl Bernhard Polzer Wolfgang Janni Brigitte Rack Lisa Wiesmüller |
spellingShingle |
Fabienne Schochter Kim Werner Cäcilia Köstler Anke Faul Marie Tzschaschel Barbara Alberter Volkmar Müller Hans Neubauer Tanja Fehm Thomas W.P. Friedl Bernhard Polzer Wolfgang Janni Brigitte Rack Lisa Wiesmüller 53BP1 Accumulation in Circulating Tumor Cells Identifies Chemotherapy-Responsive Metastatic Breast Cancer Patients Cancers metastatic breast cancer circulating tumor cells triple-negative hormone receptor Eribulin predictive biomarker |
author_facet |
Fabienne Schochter Kim Werner Cäcilia Köstler Anke Faul Marie Tzschaschel Barbara Alberter Volkmar Müller Hans Neubauer Tanja Fehm Thomas W.P. Friedl Bernhard Polzer Wolfgang Janni Brigitte Rack Lisa Wiesmüller |
author_sort |
Fabienne Schochter |
title |
53BP1 Accumulation in Circulating Tumor Cells Identifies Chemotherapy-Responsive Metastatic Breast Cancer Patients |
title_short |
53BP1 Accumulation in Circulating Tumor Cells Identifies Chemotherapy-Responsive Metastatic Breast Cancer Patients |
title_full |
53BP1 Accumulation in Circulating Tumor Cells Identifies Chemotherapy-Responsive Metastatic Breast Cancer Patients |
title_fullStr |
53BP1 Accumulation in Circulating Tumor Cells Identifies Chemotherapy-Responsive Metastatic Breast Cancer Patients |
title_full_unstemmed |
53BP1 Accumulation in Circulating Tumor Cells Identifies Chemotherapy-Responsive Metastatic Breast Cancer Patients |
title_sort |
53bp1 accumulation in circulating tumor cells identifies chemotherapy-responsive metastatic breast cancer patients |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2020-04-01 |
description |
Evidence suggests that the DNA end-binding protein p53-binding protein 1 (53BP1) is down-regulated in subsets of breast cancer. Circulating tumor cells (CTCs) provide accessible “biopsy material” to track cell traits and functions and their alterations during treatment. Here, we prospectively monitored the 53BP1 status in CTCs from 67 metastatic breast cancer (MBC) patients with HER2- CTCs and known hormone receptor (HR) status of the primary tumor and/or metastases before, during, and at the end of chemotherapeutic treatment with Eribulin. Nuclear 53BP1 staining and genomic integrity were evaluated by immunocytochemical and whole-genome-amplification-based polymerase chain reaction (PCR) analysis, respectively. Comparative analysis of CTCs from patients with triple-negative and HR+ tumors revealed elevated 53BP1 levels in CTCs from patients with HR+ metastases, particularly following chemotherapeutic treatment. Differences in nuclear 53BP1 signals did not correlate with genomic integrity in CTCs at baseline or with nuclear γH2AX signals in MBC cell lines, indicating that 53BP1 detected features beyond DNA damage. Kaplan–Meier analysis revealed an increasing association between nuclear 53BP1-positivity and progression-free survival (PFS) during chemotherapy until the final visit. Our data suggest that 53BP1 detection in CTCs could be a useful marker to capture dynamic changes of chemotherapeutic responsiveness in triple-negative and HR+ MBC. |
topic |
metastatic breast cancer circulating tumor cells triple-negative hormone receptor Eribulin predictive biomarker |
url |
https://www.mdpi.com/2072-6694/12/4/930 |
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