Shorter disease-specific survival of ER-positive breast cancer patients with high cytoplasmic Src kinase expression after tamoxifen treatment

Elsberger, B., Paravasthu, D.M., Tovey, S.M. and Edwards, J. (2012) Shorter disease-specific survival of ER-positive breast cancer patients with high cytoplasmic Src kinase expression after tamoxifen treatment. Journal of Cancer Research and Clinical Oncology, 138(2), pp. 327-332. (doi: 10.1007/s00432-011-1096-8)

Abstract

<b>Background</b> <p>Src kinase, a non-receptor tyrosine kinase, is overexpressed and highly activated in a number of human cancers and appears to show a significant relationship with breast cancer progression. Recent in vitro studies have suggested that Src kinase may be involved in tamoxifen resistance.</p> <b>Methods</b> <p>Immunohistochemistry was performed on 392 resected breast cancers using an antibody to c-Src. Expression was assessed using the weighted histoscore method.</p> <b>Results</b> <p>Forty-five percentage of breast tumours exhibited nuclear, 46% cytoplasmic and 7% membrane expression. Lymph node positivity correlated with cytoplasmic c-Src tumour expression levels (P < 0.001). Nuclear c-Src correlated negatively with cytoplasmic and membrane c-Src expression (P < 0.001, P = 0.005). High expression levels of cytoplasmic c-Src was associated with worse disease-specific survival (P = 0.026) after completing 5 years of tamoxifen therapy. However, high expression of c-Src at any cellular location did not show any association with de novo relapse on tamoxifen (c-Src nuc P = 0.906, c-Src cyto P = 0.735 and c-Src memb P = 0.791)</p> <b>Conclusions</b> <p>No translational evidence was found in this study to support a role for Src kinase in developing de novo tamoxifen resistance. However, based on our findings on late clinical outcome, patients with high cytoplasmic c-Src may be selected for continuing endocrine therapy to prevent worsening prognosis.</p>

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Elsberger, Miss Beatrix and Edwards, Professor Joanne
• Authors: Elsberger, B., Paravasthu, D.M., Tovey, S.M., and Edwards, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Journal of Cancer Research and Clinical Oncology
• ISSN: 0171-5216
• ISSN (Online): 1432-1335