Type

Other / n/a

Authors

Leonie S Young
Arnold DK Hill
Michael J Kerin
Róisín M Dwyer
Bryan T Hennessy
Jean McBryan
Sinéad Cocchiglia
Christopher Byrne
Marie McIlroy
Paul Tibbitts
and 3 others

Subjects

Medicine & Nursing

Topics
breast cancer surgery enzyme linked immunosorbent assay biomarker medicine and health sciences estrogen receptor s100 endocrine resistance

S100β as a serum marker in endocrine resistant breast cancer. (2017)

Abstract BACKGROUND: Endocrine therapy is standard treatment for estrogen receptor (ER)-positive breast cancer. However, its efficacy is limited by intrinsic and acquired resistance. Here the potential of S100β as a biomarker and inhibition of its signaling network as a therapeutic strategy in endocrine treated patients was investigated.METHODS: The expression of S100β in tissue and serum was assessed by immunohistochemistry and an enzyme-linked immunosorbent assay, respectively. The S100β signaling network was investigated in cell line models of endocrine resistance by western blot, PCR, immunoprecipitation, and chromatin-immunoprecipitation. Endocrine resistant xenografts and tumor explants from patients with resistant tumors were treated with endocrine therapy in the presence and absence of the p-Src kinase inhibitor, dasatinib.RESULTS: Tissue and serum levels of S100β were found to predict poor disease-free survival in endocrine-treated patients (n = 509, HR 2.32, 95% CI is 1.58-3.40, p < 0.0001 and n = 187, HR 4.009, 95% CI is 1.66-9.68, p = 0.002, respectively). Moreover, elevated levels of serum S100β detected during routine surveillance over the patient treatment period significantly associated with subsequent clinically confirmed disease recurrence (p = 0.019). In vivo studies demonstrated that endocrine treatment induced transcriptional regulation of S100β which was successfully disrupted with tyrosine kinase inhibition. In endocrine resistant xenografts and tumor explants from patients with endocrine resistant breast cancer, combined endocrine and dasatinib treatment reduced tumor proliferation and down-regulated S100β protein expression in comparison to endocrine treatment alone.CONCLUSIONS: S100β has potential as a new surveillance tool for patients with ER-positive breast cancer to monitor ongoing response to endocrine therapy. Moreover, endocrine resistant breast cancer patients with elevated S100β may benefit from combined endocrine and tyrosine-kinase inhibitor treatment.TRIAL REGISTRATION: ClinicalTrials.gov, NCT01840293 ). Registered on 23 April 2013. Retrospectively registered.
Collections Ireland -> Royal College of Surgeons in Ireland -> Department of Surgery
Ireland -> Royal College of Surgeons in Ireland -> Surgery Articles

Full list of authors on original publication

Leonie S Young, Arnold DK Hill, Michael J Kerin, Róisín M Dwyer, Bryan T Hennessy, Jean McBryan, Sinéad Cocchiglia, Christopher Byrne, Marie McIlroy, Paul Tibbitts and 3 others

Experts in our system

1
Leonie S Young
Royal College of Surgeons in Ireland
Total Publications: 42
 
2
Arnold D K Hill
Royal College of Surgeons in Ireland
Total Publications: 110
 
3
Michael J. Kerin
National University of Ireland Galway
Total Publications: 69
 
4
Roisin M. Dwyer
National University of Ireland Galway
Total Publications: 27
 
5
Bryan T Hennessy
Royal College of Surgeons in Ireland
Total Publications: 33
 
6
Jean McBryan
Royal College of Surgeons in Ireland
Total Publications: 10
 
7
Sinéad Cocchiglia
Royal College of Surgeons in Ireland
Total Publications: 10
 
8
Christopher Byrne
Royal College of Surgeons in Ireland
Total Publications: 13
 
9
Marie McIlroy
Royal College of Surgeons in Ireland
 
10
Paul Tibbitts
Royal College of Surgeons in Ireland
Total Publications: 11