title: Osteopontin splice variants are differential predictors of breast cancer treatment responses.
abstract: Osteopontin is a marker for breast cancer progression, which in previous studies has also been associated with resistance to certain anti-cancer therapies. It is not known which splice variants may mediate treatment resistance.
  
  
  
  Here we analyze the association of osteopontin variant expression before treatment, differentiated according to immunohistochemistry with antibodies to exon 4 and to the osteopontin-c splice junction respectively, with the ensuing therapy responses in 119 Polish breast cancer patients who presented between 1995 and 2008.
  
  
  
  We found from Cox hazard models, logrank test and Wilcoxon test that osteopontin exon 4 was associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil). Osteopontin-c is prognostic, but falls short of being a significant predictor for sensitivity to treatment.
  
  
  
  The addition of osteopontin splice variant immunohistochemistry to standard pathology work-ups has the potential to aid decision making in breast cancer treatment.
authors.affiliation: Department of Pathology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Zduniak
authors.affiliation: Department of General and Oncological Surgery, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Anil
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: Department of General and Oncological Surgery, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Siddarth
authors.initials: S
authors.lastname: Agrawal
authors.affiliation: Division of Biostatistics and Epidemilogy, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Md Monir
authors.initials: MM
authors.lastname: Hossain
authors.affiliation: Department of Pathology, Wroclaw Medical University, Wroclaw, Poland. ziolkows@interia.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ziolkowski
authors.affiliation: University of Cincinnati Academic Health Center, College of Pharmacy, 3225 Eden Avenue, Cincinnati, OH, 45267-0004, USA. georg.weber@uc.edu.
authors.forename: Georg F
authors.initials: GF
authors.lastname: Weber
mesh_terms: D017398:Alternative Splicing; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003520:Cyclophosphamide / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D008727:Methotrexate / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D011044:Poland / Q000453:epidemiology; D011379:Prognosis; D016016:Proportional Hazards Models; D020033:Protein Isoforms / Q000378:metabolism; D012189:Retrospective Studies; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D020033:Protein Isoforms; C506895:SPP1 protein, human; D013629:Tamoxifen; D053495:Osteopontin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate
keywords: Breast cancer; Chemotherapy; Hormone therapy; Immunohistochemistry; Radiation therapy; Tumor progression marker