S100β as a serum marker in endocrine resistant breast cancer

BMC Medicine

Research Article

Bryan T. Hennessy¹  Arnold D. Hill²  Paul Tibbitts²  Róisín M. Dwyer³  Michael J. Kerin³  Marie McIlroy⁴  Sinéad Cocchiglia⁴  Leonie S. Young⁴  Éamon Hughes⁴  Jean McBryan⁴  Fiona T. Bane⁴  Sara Charmsaz⁴  Christopher Byrne⁴ 

[1] Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland;Department of Surgery, Beaumont Hospital, Dublin, Ireland;Department of Surgery, Lambe Institute for Translational Researcich, National University of Ireland Galway, Galway, Ireland;Endocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, Dublin, Ireland;

关键词: Biomarker;    Endocrine resistance;    Breast cancer;    S100β;    Estrogen receptor;   

DOI  :  10.1186/s12916-017-0836-2

 received in 2016-11-14, accepted in 2017-03-14,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundEndocrine 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.MethodsThe 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.ResultsTissue 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.ConclusionsS100β 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 registrationClinicalTrials.gov, NCT01840293). Registered on 23 April 2013. Retrospectively registered.

【 授权许可】

CC BY   
© The Author(s). 2017