Calpain-1 is associated with adverse relapse free survival in breast cancer: a confirmatory study.
OBJECTIVE
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.


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.
Department of Clinical Oncology, School of Medicine, Division of Cancer and Stem Cells, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Xuan
X
Pu
Department of Clinical Oncology, School of Medicine, Division of Cancer and Stem Cells, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Sarah J
SJ
Storr
Department of Clinical Oncology, School of Medicine, Division of Cancer and Stem Cells, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Narmeen S
NS
Ahmad
Department of Clinical Oncology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Stephen Y
SY
Chan
Department of Clinical Oncology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Paul M
PM
Moseley
Department of Cancer Pharmacology, Northern Institute for Cancer Research, Newcastle University, Newcastle, UK.
Despina
D
Televantou
Department of Cancer Pharmacology, Northern Institute for Cancer Research, Newcastle University, Newcastle, UK.
Nicola
N
Cresti
Faculty of Pharmacy, University of Sydney, Sydney, NSW, Australia.
Alan
A
Boddy
Department of Histopathology, School of Medicine, Division of Cancer and Stem Cells, University of Nottingham, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Ian O
IO
Ellis
Department of Clinical Oncology, School of Medicine, Division of Cancer and Stem Cells, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Stewart G
SG
Martin
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002154:Calpain / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D046888:Tissue Array Analysis; D000068878:Trastuzumab / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002154:Calpain; C484806:CAPN1 protein, human; D000068878:Trastuzumab
breast cancer; calpain-1; relapse free survival; targeted therapy; trastuzumab