title: Association between SPARC mRNA expression, prognosis and response to neoadjuvant chemotherapy in early breast cancer: a pooled in-silico analysis.
abstract: BACKGROUND
  SPARC is an important regulator of the extracellular matrix and has been suggested to improve delivery of albumin-bound cytotoxics. However, little is known regarding its role in breast cancer (BC).
  
  
  METHODS
  We conducted a pooled analysis of publically available datasets, in which BC patients who received no systemic therapy or received neoadjuvant chemotherapy were eligible. Patients were assigned to molecular subtypes using PAM-50. We computed a SPARC module (SPARC7), composed of genes with an absolute correlation with SPARC >0.7. In the systemically untreated cohort, we evaluated 1) expression of SPARC/SPARC7 according to breast cancer subtype, 2) association between SPARC/SPARC7 and biological processes related to proliferation, immune and stroma, and 3) association between SPARC/SPARC7 and relapse-free survival in a Cox model in all patients and in the different molecular subtypes adjusted for tumor size, nodal status, histological grade, and age. In the neoadjuvant cohort, we evaluated the association between SPARC and pCR in a logistic regression model, adjusted for the same clinicopathologic factors.
  
  
  RESULTS
  948 (10 datasets), and 791 (8 datasets) patients were included in the systemically untreated and neoadjuvant cohorts, respectively. High SPARC expression was associated with small tumor size, low histological grade and luminal-A tumors (all p<0.0001). There was a positive correlation between SPARC and stroma-related modules but negative correlation with proliferation modules. High SPARC expression was associated with poor prognosis in patients with basal and HER2+ breast cancer even after adjusting for clinicopathologic parameters. In the neoadjuvant cohort, a subgroup analysis suggested that high SPARC is associated with low rates of pCR in the HER2 subtype. Same results were observed on replacing SPARC by SPARC7.
  
  
  CONCLUSIONS
  This analysis suggests a potential role of SPARC in determining prognosis and response to primary chemotherapy in early BC. This information could guide further development of albumin-bound cytotoxics in BC.
authors: Breast Cancer Translational Research Laboratory, JC Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors: Hatem A
authors: HA
authors: Azim
authors: Sandeep
authors: S
authors: Singhal
authors: Michail
authors: M
authors: Ignatiadis
authors: Christine
authors: C
authors: Desmedt
authors: Debora
authors: D
authors: Fumagalli
authors: Isabelle
authors: I
authors: Veys
authors: Denis
authors: D
authors: Larsimont
authors: Martine
authors: M
authors: Piccart
authors: Stefan
authors: S
authors: Michiels
authors: Christos
authors: C
authors: Sotiriou
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D003198:Computer Simulation; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D016017:Odds Ratio; D015676:Osteonectin / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012008:Recurrence
chemical_list: D015676:Osteonectin; D012333:RNA, Messenger
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