scholarly journals Circulating Tumor Cells in Metastatic Breast Cancer: Clinical Applications and Future Possibilities

2020 ◽  
Vol 10 (9) ◽  
pp. 3311
Author(s):  
Maggie Banys-Paluchowski ◽  
Florian Reinhardt ◽  
Tanja Fehm
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Therapy Monitoring ◽  
Metastatic Breast ◽  
Study Groups ◽  
Clinical Applications ◽  
Response To Treatment ◽  
Cellsearch System

Circulating tumor cells (CTCs) have gained importance as an emerging biomarker in solid tumors in the last two decades. Several detection assays have been introduced by various study groups, with EpCAM-based CellSearch system being the most widely used and standardized technique. In breast cancer, detection of CTCs correlates with clinical outcome in early and metastatic settings. CTC persistence beyond first cycle of palliative chemotherapy indicates poor response to treatment in metastatic situation. Beyond prognostication and therapy monitoring, CTC counts can guide treatment decisions in hormone receptor positive HER2-negative metastatic breast cancer. Furthermore, CTC-based therapy interventions are currently under investigation in clinical trials. In this review, we focus on the current state of knowledge and possible clinical applications of CTC diagnostics in patients with metastatic breast cancer.

Assessment of γH2AX levels in circulating tumor cells in patients treated with veliparib in combination with doxorubicin and cyclophosphamide in metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2582-2582
Author(s):  
Antoinette R. Tan ◽  
Deborah Toppmeyer ◽  
Serena Tsan-Lai Wong ◽  
Hongxia Lin ◽  
Murugesan Gounder ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Brca Mutation ◽  
Parp Inhibitor ◽  
Metastatic Breast ◽  
Chemotherapeutic Agents ◽  
Response To Treatment

2582 Background: Veliparib (V) is a potent PARP inhibitor that delays repair of DNA damage induced by chemotherapeutic agents. In metastatic breast cancer pts, we evaluated V with doxorubicin (A) and cyclophosphamide (C) given both on day 1 with V at 100 mg po BID for 7 days post-chemotherapy every 21 days, to increase DNA damage. We report use of γH2AX, (phosphorylated histone protein), a marker of DNA double-strand breaks, in circulating tumor cells (CTCs) to assess DNA damage. We evaluated number of CTCs and percentage of γH2AX-positive CTCs pre- and post-treatment. Methods: Eligibility included prior A ≤ 300 mg/m2 and EF ≥ 50%. Further A was omitted after a cumulative dose of 420 mg/m2. Primary objective was to assess DNA damage response to treatment by measuring γH2AX-positive CTCs during cycle 1 on days 1 (pre-treatment), 2, 7, and 14. Cell Search System was used to enumerate CTCs. γH2AX was quantitated using a validated assay. Results: Eleven pts enrolled. Median age was 53 (34 – 73); median ECOG PS 1 (0 – 2); there were 1 ER-negative/HER2+, 4 triple-negative (BRCA2+, n =1), and 6 ER+/PR+/HER2-negative (BRCA2+, n =2) tumors. Most common drug-related toxicities were grade (gr) 4 neutropenia, gr 2 anemia and thrombocytopenia, and gr 1 nausea and vomiting. In BRCA2+ pts, there were 2 PRs and 1 SD. In BRCA wt or unknown status, 5 pts had SD ≥ 3 mo and there were 3 PDs. CTCs (≥ 8) were detected in 10/11 pts on days 1 and 2. Day 7 samples were not obtainable in 2 pts. On day 7, 1/8 pts had 0 CTCs and rest had ≥ 3 CTCs. A decrease in CTCs (p < 0.0001) occurred from day 1 (median: 22, range, 8-1216) to day 7 (median: 5, range 3-37). At baseline, 7 pts had ≥ 10% γH2AX-positive CTCs. Fraction of CTCs positive for γH2AX increased to ≥ 50% by day 7 in 6/7 pts and persisted to day 14 in 5 pts. Conclusions: The toxicity profile of V 100 mg BID days 1-7 with AC (60/600 mg/m2) on day 1 on a 21-day cycle was expected. Objective antitumor activity was seen in BRCA mutation carriers. CTCs decreased and percentage of γH2AX-positive CTCs increased after combination treatment with a PARP inhibitor and chemotherapy. This observation is notable and we plan to extend dosing of V to 14 days. This work is supported by NCI U01-CA132194. Clinical trial information: NCT00740805.

scholarly journals RNA Profiles of Circulating Tumor Cells and Extracellular Vesicles for Therapy Stratification of Metastatic Breast Cancer Patients

2018 ◽  
Vol 64 (7) ◽  
pp. 1054-1062 ◽  
Author(s):  
Corinna Keup ◽  
Pawel Mach ◽  
Bahriye Aktas ◽  
Mitra Tewes ◽  
Hans-Christian Kolberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Extracellular Vesicles ◽  
Therapy Monitoring ◽  
Quantitative Polymerase Chain Reaction ◽  
Metastatic Breast ◽  
Therapy Stratification

Abstract BACKGROUND Liquid biopsies are discussed to provide surrogate markers for therapy stratification and monitoring. We compared messenger RNA (mRNA) profiles of circulating tumor cells (CTCs) and extracellular vesicles (EVs) in patients with metastatic breast cancer (MBC) to estimate their utility in therapy management. METHODS Blood was collected from 35 hormone receptor-positive/HER2-negative patients with MBC at the time of disease progression and at 2 consecutive staging time points. CTCs were isolated from 5 mL of blood by positive immunomagnetic selection, and EVs from 4 mL of plasma by a membrane affinity-based procedure. mRNA was reverse transcribed, preamplified, and analyzed for 18 genes by multimarker quantitative polymerase chain reaction (qPCR) assays. RNA profiles were normalized to healthy donor controls (n = 20), and results were correlated with therapy outcome. RESULTS There were great differences in mRNA profiles of EVs and CTCs, with only 5% (21/403) of positive signals identical in both fractions. Transcripts involved in the PI3K signaling pathway were frequently overexpressed in CTCs, and AURKA, PARP1, and SRC signals appeared more often in EVs. Of all patients, 40% and 34% showed ERBB2 and ERBB3 signals, respectively, in CTCs, which was significantly associated with disease progression (P = 0.007). Whereas MTOR signals in CTCs significantly correlated with response (P = 0.046), signals in EVs indicated therapy failure (P = 0.011). The presence of AURKA signals in EVs seemed to be a marker for the indication of unsuccessful treatment of bone metastasis. CONCLUSIONS These results emphasize the potential of CTCs and EVs for therapy monitoring and the need for critical evaluation of the implementation of any liquid biopsy in clinical practice.

scholarly journals Liquid Biopsy in Metastatic Breast Cancer: Current Role of Circulating Tumor Cells and Circulating Tumor DNA

2021 ◽  
Author(s):  
Maggie Banys-Paluchowski ◽  
Tanja N. Fehm ◽  
Donata Grimm-Glang ◽  
Achim Rody ◽  
Natalia Krawczyk
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Therapy Monitoring ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Her2 Positive ◽  
Tumor Dna

Background In metastatic breast cancer, blood-based diagnostics have become a major focus of oncological research in the last two decades. Detection of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) has the potential to improve prognosis assessment and complement standard therapy monitoring tools. Summary To date, several large analyses have confirmed high CTC counts as an independent prognostic factor. Persistently high CTC numbers during systemic treatment are associated with early progression but it remains to be clarified which therapeutic options should be offered to such patients since the SWOG 0500 trial failed to show benefit from early switch to another chemotherapy regimen in patients with CTC persistence. In comparison, evidence on the prognostic value of ctDNA is still limited. Most importantly, liquid biopsy-guided treatment interventions have been investigated in several trials. In patients with hormone receptor positive HER2 negative metastatic breast cancer CTC-driven therapy choices resulted in similar PFS to physician’s choice treatment. Recently, the DETECT III trial has shown that patients with HER2 negative metastatic breast cancer and HER2 positive CTCs may benefit from targeted anti-HER2 treatment with lapatinib. ctDNA-driven therapy selection has already been approved in clinical routine: alpelisib is the first targeted treatment indicated on the basis of a ctDNA test. Key messages CTCs and ctDNA predict clinical outcome and have a potential to improve therapy choices in metastatic breast cancer.

scholarly journals Detection of Circulating Tumor Cells in Peripheral Blood of Patients with Metastatic Breast Cancer: A Validation Study of the CellSearch System

2007 ◽  
Vol 13 (3) ◽  
pp. 920-928 ◽  
Author(s):  
Sabine Riethdorf ◽  
Herbert Fritsche ◽  
Volkmar Müller ◽  
Thomas Rau ◽  
Christian Schindlbeck ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Validation Study ◽  
Peripheral Blood ◽  
Metastatic Breast ◽  
Cellsearch System

The impact of HER2 phenotype of circulating tumor cells in metastatic breast cancer: a study in 107 patients

2014 ◽  
Vol 74 (S 01) ◽  
Author(s):  
M Wallwiener ◽  
AD Hartkopf ◽  
S Riethdorf ◽  
J Nees ◽  
FA Taran ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
The Impact
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