Calpain-1 is associated with adverse relapse free survival in breast cancer: a confirmatory study
Xuan Pu1, Sarah J Storr1, Narmeen S Ahmad1
1Department of Clinical Oncology, School of Medicine, Division of Cancer and Stem Cells, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Aims:
Calpain-1 is a ubiquitously expressed calcium-activated intracellular cysteine protease. Altered expression of calpain system proteins has been implicated in cancer progression and response to chemotherapy.
Methods And Results:
The aim of the current study was to confirm previous data that suggested that calpain-1 expression is associated with relapse-free survival in trastuzumab-treated breast cancer patients (n = 93). An expanded patient cohort from Nottingham (n = 194; including 72 of the previous cohort) and an independent patient cohort from Newcastle (n = 87) were used. All patients received trastuzumab following adjuvant therapy according to local guidelines with expression of calpain-1 investigated using standard immunohistochemistry. Results show that calpain-1 expression is associated with relapse-free survival in both the Nottingham (P = 0.01) and Newcastle (P = 0.019) cohorts, with high expression associated with adverse relapse-free survival. Expression was also associated with poor relapse-free survival when patient cohorts were combined (n = 281, P = 0.01). Calpain-1 remained, from multivariate analysis, an independent marker for relapse-free survival in the Newcastle cohort [hazard ratio (HR) = 5.169; 95% confidence interval (CI) 1.468-18.200; P = 0.011].
Conclusions:
Calpain-1 expression is associated with poor relapse-free survival in breast cancer patients treated with trastuzumab. Further work is warranted to standardize and develop methodology with a view to potentially introducing assessment of this important biomarker into clinical practice.
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