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||Tumor Intrinsic Subtype is Reflected in Cancer-Adjacent Tissue.
||Casbas-Hernandez P, Sun X, Roman-Perez E, D'arcy M, Sandhu R, Hishida A, McNaughton KK, Yang XR, Makowski L, Sherman ME, Figueroa JD, Troester MA
||Cancer Epidemiol Biomarkers Prev
||2014 Dec 2
||Introduction: Overall survival of early-stage breast cancer (BC) patients is similar for those who undergo breast conserving therapy (BCT) and mastectomy, however, 10-15% of women undergoing BCT suffer ipsilateral breast tumor recurrence. The risk of recurrence may vary with BC 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 data sets to study gene expression data in cancer-adjacent tissue from invasive BC patients. Complementary in vitro cocultures were used to study cell-cell communication between fibroblasts and specific BC 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. While 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, while triple negative BCs 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 BCs are reflected in the surrounding histologically-normal tissue. This commonality between tumor and cancer-adjacent tissue may underlie second primaries and local recurrences. Impact: Biomarkers derived from cancer-adjacent tissue may be helpful in defining personalized surgical strategies or in predicting recurrence risk.