Plasma DNA integrity indicates response to neoadjuvant chemotherapy in patients with locally confined breast cancer

2013 ◽  
Vol 51 (01) ◽  
pp. 59-62 ◽  
Author(s):  
Julia Lehner ◽  
Oliver J. Stötzer ◽  
Debora M.I. Fersching ◽  
Dorothea Nagel ◽  
Stefan Holdenrieder
2013 ◽  
Vol 425 ◽  
pp. 206-211 ◽  
Author(s):  
Julia Lehner ◽  
Oliver J. Stötzer ◽  
Debora Fersching ◽  
Dorothea Nagel ◽  
Stefan Holdenrieder

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21067-e21067
Author(s):  
Oliver J. Stoetzer ◽  
Holdenrieder Stefan ◽  
Julia Lehner ◽  
Deborah Fersching ◽  
Christoph Salat

e21067 Background: In breast cancer patients undergoing neoadjuvant chemotherapy before surgery, biomarkers for predicting the response to the therapy are highly needed. Methods: Concentrations of ALU115, ALU247 and DNA integrity were analyzed in prospectively collected plasma of 68 patients with localized breast cancer (UICC II and III), of 47 patients with metastatic breast cancer and 28 healthy women as controls. In all 68 patients with breast cancer who had completed the course of chemotherapy until surgery, DNA and tumor biomarkers CEA and CA 15-3 were evaluated concerning response to therapy (no change, NC: N=18; partial remission, PR: N=35; complete remission, CR: 15). Results: Plasma levels of ALU 115 and ALU 247 were significantly higher in patients with localized (medians 16.3 and 16.8 ng/mL) and metastasized breast cancer (22.2 and 29.8 ng/mL) than in healthy controls (1.8 and 1.9 ng/mL). However, plasma DNA integrity showed no significant differences between the diagnostic groups. AUCs in ROC curves for discrimination of localized breast cancer from healthy controls were 96% for ALU 115 and ALU 247, respectively, and 60% for DNA integrity. Concerning therapy response, pretherapeutic ALU 115, 247, and DNA integrity and also CEA and CA 15-3 were not significantly different when patients with and without remission (CR vs PR+NC and CR+PR vs NC) were compared. Conclusions: While plasma DNA levels are valuable for discrimination of breast cancer patients from controls, pretherapeutic DNA integrity provides no additive diagnostic information nor indicates response to neoadjuvant therapy.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xu Yang ◽  
Geng-Xi Cai ◽  
Bo-Wei Han ◽  
Zhi-Wei Guo ◽  
Ying-Song Wu ◽  
...  

AbstractGene expression signatures have been used to predict the outcome of chemotherapy for breast cancer. The nucleosome footprint of cell-free DNA (cfDNA) carries gene expression information of the original tissues and thus may be used to predict the response to chemotherapy. Here we carried out the nucleosome positioning on cfDNA from 85 breast cancer patients and 85 healthy individuals and two cancer cell lines T-47D and MDA-MB-231 using low-coverage whole-genome sequencing (LCWGS) method. The patients showed distinct nucleosome footprints at Transcription Start Sites (TSSs) compared with normal donors. In order to identify the footprints of cfDNA corresponding with the responses to neoadjuvant chemotherapy in patients, we mapped on nucleosome positions on cfDNA of patients with different responses: responders (pretreatment, n = 28; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 12) and nonresponders (pretreatment, n = 10; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 10). The coverage depth near TSSs in plasma cfDNA differed significantly between responders and nonresponders at pretreatment, and also after neoadjuvant chemotherapy treatment cycles. We identified 232 TSSs with differential footprints at pretreatment and 321 after treatment and found enrichment in Gene Ontology terms such as cell growth inhibition, tumor suppressor, necrotic cell death, acute inflammatory response, T cell receptor signaling pathway, and positive regulation of vascular endothelial growth factor production. These results suggest that cfDNA nucleosome footprints may be used to predict the efficacy of neoadjuvant chemotherapy for breast cancer patients and thus may provide help in decision making for individual patients.


2021 ◽  
Vol 32 ◽  
pp. S49
Author(s):  
S. Di Cosimo ◽  
C. Depretto ◽  
R. Miceli ◽  
P. Baili ◽  
M. Sant ◽  
...  

2020 ◽  
Vol 46 (2) ◽  
pp. e37-e38
Author(s):  
Imen Zawati ◽  
Sabrine Boukhris ◽  
Marwa Manai ◽  
Aida Goucha ◽  
Ilhem Bettaieb ◽  
...  

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