title: Expression of secreted protein acidic and rich in cysteine (SPARC) in breast cancer and response to neoadjuvant chemotherapy.
abstract: BACKGROUND
  Secreted protein acidic and rich in cysteine (SPARC) has been suggested as a new biomarker and therapeutic target in breast cancer, as well as other tumor types.
  
  
  METHODS
  We evaluated the frequency of SPARC expression among different molecular breast cancer subtypes and its role for therapy response after neoadjuvant chemotherapy. In this study, pretherapeutic core biopsies of 667 patients from the neoadjuvant GeparTrio trial were evaluated for SPARC expression by immunohistochemistry using a standardized immunoreactive score (IRS).
  
  
  RESULTS
  An increased SPARC expression (IRS ≥6) was observed in 26% of all tumors. In triple-negative tumors, SPARC expression was increased in 37% of tumors, compared with other molecular subtypes (23% HR+/HER2-, 29% HR+/HER2+ and 22% HR-/HER2+; P = 0.038). Increased SPARC expression was associated with an increased pathological complete response (pCR) rate of 27%, compared with 15% in tumors with low SPARC expression (P < 0.001). In the triple-negative subgroup, pCR rates were 47% in tumors with high SPARC expression, compared with 26% in tumors with low SPARC expression (P = 0.032). In multivariable analysis, SPARC was independently predictive in the overall population (P = 0.010) as well as the triple-negative subgroup (P = 0.036).
  
  
  CONCLUSIONS
  SPARC is frequently expressed in breast cancer with triple-negative breast cancer revealing the highest expression rate. High SPARC expression of the primary tumor is associated with a higher chance of achieving a pathological complete remission after TAC or TAC-NX chemotherapy. As SPARC is an albumin-binding protein and might mediate intratumoral accumulation of albumin bound drugs, SPARC should be further evaluated as a predictive marker especially for response to albumin-bound drugs like nab-paclitaxel.
  
  
  BACKGROUND
  NCT00544765.
authors.affiliation: Institute of Pathology, Charité-Universitätsmedizin Berlin, Berlin.
authors.forename: J L
authors.initials: JL
authors.lastname: Lindner
authors.affiliation: German Breast Group, Neu-Isenburg; Department of Oncology, Klinikum Offenbach, Offenbach.
authors.forename: S
authors.initials: S
authors.lastname: Loibl
authors.affiliation: Institute of Pathology, Charité-Universitätsmedizin Berlin, Berlin. Electronic address: carsten.denkert@charite.de.
authors.forename: C
authors.initials: C
authors.lastname: Denkert
authors.affiliation: Department of Gynecology, Kliniken-Essen-Mitte, Essen.
authors.forename: B
authors.initials: B
authors.lastname: Ataseven
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen.
authors.forename: P A
authors.initials: PA
authors.lastname: Fasching
authors.affiliation: Institute of Pathology, Charité-Universitätsmedizin Berlin, Berlin.
authors.forename: B M
authors.initials: BM
authors.lastname: Pfitzner
authors.affiliation: Department of Gynecology, Klinikum Südstadt Rostock, Rostock.
authors.forename: B
authors.initials: B
authors.lastname: Gerber
authors.affiliation: German Breast Group, Neu-Isenburg.
authors.forename: S
authors.initials: S
authors.lastname: Gade
authors.affiliation: Institute of Pathology, Charité-Universitätsmedizin Berlin, Berlin.
authors.forename: S
authors.initials: S
authors.lastname: Darb-Esfahani
authors.affiliation: Institute of Pathology, Charité-Universitätsmedizin Berlin, Berlin.
authors.forename: B V
authors.initials: BV
authors.lastname: Sinn
authors.affiliation: Department of Obstetrics and Gynecology, Universitätsklinikum Ulm, Ulm.
authors.forename: J
authors.initials: J
authors.lastname: Huober
authors.affiliation: Department of Pathology, Zentrum für Pathologie, Zytologie und Molekularpathologie, Neuss.
authors.forename: K
authors.initials: K
authors.lastname: Engels
authors.affiliation: Oncological Center, Bethanien-Hospital, Frankfurt am Main.
authors.forename: H
authors.initials: H
authors.lastname: Tesch
authors.affiliation: Department of Obstetrics and Gynecology, Goethe-Universität, Frankfurt/Main.
authors.forename: T
authors.initials: T
authors.lastname: Karn
authors.affiliation: Institute of Pathology, Klinikum Südstadt, Rostock.
authors.forename: F
authors.initials: F
authors.lastname: Pommerenke
authors.affiliation: Department of Obstetrics and Gynecology, Universitätsklinikum Schleswig-Holstein, Lübeck.
authors.forename: C
authors.initials: C
authors.lastname: Liedtke
authors.affiliation: Department of Obstetrics and Gynecology, Helios Klinikum Berlin-Buch, Berlin.
authors.forename: M
authors.initials: M
authors.lastname: Untch
authors.affiliation: Department of Gynecology, Universitätsklinikum Hamburg-Eppendorf, Hamburg.
authors.forename: V
authors.initials: V
authors.lastname: Müller
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-Universität München, München.
authors.forename: B
authors.initials: B
authors.lastname: Rack
authors.affiliation: Department of Obstetrics and Gynecology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schem
authors.affiliation: German Breast Group, Neu-Isenburg; Department of Obstetrics and Gynecology, Goethe-Universität, Frankfurt/Main.
authors.forename: G
authors.initials: G
authors.lastname: von Minckwitz
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D015676:Osteonectin / Q000096:biosynthesis*; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality*
chemical_list: D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D004317:Doxorubicin; D015676:Osteonectin; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids; C577241:SPARC protein, human; C508053:ERBB2 protein, human
keywords: SPARC; breast cancer; neoadjuvant chemotherapy; pCR