Introduction/Background Evidence suggests that the DNA end-binding protein p53-binding protein 1 (53BP1) expression in breast cancer is associated with poor prognosis, especially in triple-negative breast cancer (TNBC). Circulating tumor cells (CTCs) provide accessible ‘biopsy material’ to track cell traits and functions and their alterations during treatment.
Methodology We prospectively monitored the 53BP1 status, as a parameter for intact DNA damage response, in CTCs from 63 metastatic breast cancer (MBC) patients with HER2- CTCs before, during, and at the end of chemotherapeutic treatment with Eribulin in the DETECT-IV trail. Nuclear 53BP1 staining and genomic integrity were evaluated by immunocytochemical and whole-genome-amplification-based polymerase chain reaction (PCR) analysis. We used mean 53BP1 scores in CTC samples as dividing criteria, i.e. compared patients with 53BP1 scores <50% and ≥50%. We analyzed PFS of the patients from these two groups using scores obtained with samples at different time points during the study.
Results We found a decline of mean CTC numbers from baseline to 12 weeks of treatment but a dramatic rise at the final visit due to disease progression in 10/13 of the cases (mean CTC-values at baseline: 18, 2nd visit: 2, final visit: 118). Comparative analysis of CTCs from patients with 15 triple-negative and 48 hormone receptor positive tumors revealed elevated 53BP1 levels in CTCs from patients with HR+ metastases, particularly following chemotherapeutic treatment. Kaplan–Meier analysis between nuclear 53BP1-positivity in CTCs and progression-free survival (PFS) revealed an increasing association during chemotherapy until last examination (p=0.065).
Conclusion 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.
Disclosures FSch received speaker honoraria and a travel grant from Roche, Novartis, Pfizer and Lilly.
VM speaker honoraria from Amgen, Astra Zeneca, Celgene, Daiichi-Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, and consultancy honoraria from Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Tesaro, and Nektar, as well as institutional research support from Novartis, Roche, Seattle Genetics, and Genentech. Otherwise, no potential conflicts of interests were disclosed by the authors.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.