title: Tumor intrinsic subtype is reflected in cancer-adjacent tissue.
abstract: BACKGROUND
  Overall survival of early-stage breast cancer patients is similar for those who undergo breast-conserving therapy (BCT) and mastectomy; however, 10% to 15% of women undergoing BCT suffer ipsilateral breast tumor recurrence. The risk of recurrence may vary with breast cancer subtype. Understanding the gene expression of the cancer-adjacent tissue and the stromal response to specific tumor subtypes is important for developing clinical strategies to reduce recurrence risk.
  
  
  METHODS
  We utilized two independent datasets to study gene expression data in cancer-adjacent tissue from invasive breast cancer patients. Complementary in vitro cocultures were used to study cell-cell communication between fibroblasts and specific breast cancer subtypes.
  
  
  RESULTS
  Our results suggest that intrinsic tumor subtypes are reflected in histologically normal cancer-adjacent tissue. Gene expression of cancer-adjacent tissues shows that triple-negative (Claudin-low or basal-like) tumors exhibit increased expression of genes involved in inflammation and immune response. Although such changes could reflect distinct immune populations present in the microenvironment, altered immune response gene expression was also observed in cocultures in the absence of immune cell infiltrates, emphasizing that these inflammatory mediators are secreted by breast-specific cells. In addition, although triple-negative breast cancers are associated with upregulated immune response genes, luminal breast cancers are more commonly associated with estrogen-response pathways in adjacent tissues.
  
  
  CONCLUSIONS
  Specific characteristics of breast cancers are reflected in the surrounding histologically normal tissue. This commonality between tumor and cancer-adjacent tissue may underlie second primaries and local recurrences.
  
  
  CONCLUSIONS
  Biomarkers derived from cancer-adjacent tissue may be helpful in defining personalized surgical strategies or in predicting recurrence risk.
authors.affiliation: Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Patricia
authors.initials: P
authors.lastname: Casbas-Hernandez
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Xuezheng
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Erick
authors.initials: E
authors.lastname: Roman-Perez
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Monica
authors.initials: M
authors.lastname: D'Arcy
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Rupninder
authors.initials: R
authors.lastname: Sandhu
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Asahi
authors.initials: A
authors.lastname: Hishida
authors.affiliation: Department of Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Kirk K
authors.initials: KK
authors.lastname: McNaughton
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland.
authors.forename: Xiaohong R
authors.initials: XR
authors.lastname: Yang
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Liza
authors.initials: L
authors.lastname: Makowski
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland.
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
authors.affiliation: Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. troester@unc.edu.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Troester
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005802:Genes, MHC Class II / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics*; D009364:Neoplasm Recurrence, Local; D046888:Tissue Array Analysis; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000473:pathology; D059016:Tumor Microenvironment / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins