Casbas-Hernandez Patricia, Sun Xuezheng, Roman-Perez Erick, D'Arcy Monica, Sandhu Rupninder, Hishida Asahi, McNaughton Kirk K, Yang Xiaohong R, Makowski Liza, Sherman Mark E, Figueroa Jonine D, Troester Melissa A
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.
Cancer Epidemiol Biomarkers Prev. 2015 Feb;24(2):406-14. doi: 10.1158/1055-9965.EPI-14-0934. Epub 2014 Dec 2.
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.
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.
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.
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.
Biomarkers derived from cancer-adjacent tissue may be helpful in defining personalized surgical strategies or in predicting recurrence risk.
早期乳腺癌患者接受保乳治疗（BCT）和乳房切除术的总生存率相似；然而，接受BCT的女性中有10%至15%会发生同侧乳腺肿瘤复发。复发风险可能因乳腺癌亚型而异。了解癌旁组织的基因表达以及基质对特定肿瘤亚型的反应对于制定降低复发风险的临床策略很重要。
我们利用两个独立的数据集研究浸润性乳腺癌患者癌旁组织中的基因表达数据。使用互补的体外共培养来研究成纤维细胞与特定乳腺癌亚型之间的细胞间通讯。
我们的结果表明，内在肿瘤亚型在组织学上正常的癌旁组织中有所体现。癌旁组织的基因表达显示，三阴性（Claudin低表达或基底样）肿瘤表现出参与炎症和免疫反应的基因表达增加。虽然这种变化可能反映了微环境中存在的不同免疫群体，但在没有免疫细胞浸润的共培养中也观察到免疫反应基因表达的改变，这强调了这些炎症介质是由乳腺特异性细胞分泌的。此外，虽然三阴性乳腺癌与免疫反应基因上调有关，但管腔型乳腺癌在相邻组织中更常与雌激素反应途径有关。
乳腺癌的特定特征在周围组织学正常的组织中有所体现。肿瘤与癌旁组织之间的这种共性可能是第二原发性肿瘤和局部复发的基础。
源自癌旁组织的生物标志物可能有助于确定个性化的手术策略或预测复发风险。
