Abstract PS4-08-19: Different gene expression between breast cancer and adjacent normal breast tissue according to breast cancer subtype

Abstract Introduction: Through the remarkable advances in genomics, we have identified many of the genetic alterations causing breast cancer(BC) development. Moreover, recent research revealed that these genetic alterations have been continually occurring and accumulating long before cancer develops. However, the role of normal breast tissue in BC patients has been veiled. In this study, we aimed to determine gene expression affecting cancer development from normal breast tissue using paired breast normal-cancer tissues. Methods: We collected BC-normal paired tissues which harvested during curative BC surgery since August 2008 to February 2013. Using these samples, we performed RNASeq, nCounter customized gene expression analysis and WES. Results: Of 134 BC tissues, 121 tumor tissues and 51 normal tissues were analyzed using nCounter method. Among these samples, 50 were paired BC-normal tissues. In 51 normal breast tissues, there was all normal like intrinsic subtype. Further DEG analysis according to tumor subtype, there was no significant different in normal tissues among BC subtype. We also analyzed the different gene expression between tumor-normal tissues according to BC subtypes. In HR+HER2- BC, MMP11, BRIC5 and KNTC2 were significantly upregulated in tumor tissue compared to normal tissue (all adjusted P value 0.05 and log2FoldChange 1). In HR+HER2+BC, only MMP11 was upregulated but SFRP1, ELF5 and FOXC1 expression decreased. TNBC had significantly different gene expression compared to normal breast tissue. Ten genes (ANLN, APOBEC3B, BIRC5, CDCA1,CEP55, EXO1, KIF2C, KNTC2, MYBL2 and ORM2) were overexpressed in tumor tissue whereas seven genes(AR, ESR1, ERBB4, MLPH, PGR, PIP and SCUBE2) expression was decreased. In HR-HER2+BC, ANLN overexpression but ESR1, MIA and KRT14 downregulation were observed. Further DEG analysis according to survival outcome, upregulation of MMP11 and MKI67 were associated to BC recurrence but BIRC5, CEP55M EXO1 and KNTC2 overexpression were associated to BC recurrence free survival regardless of BC subtypes (all adjusted P value 0.05 and log2FoldChange 1). Conclusion: Although there were no different gene expression in normal breast tissues according to BC subtype, significant difference of gene expression between tumor and normal tissues were observed according to BC subtype. In particular, TNBC had the highest number of genes with differential expression in tumor and normal tissue. In addition, different expression of some genes was also associated to BC recurrence. Citation Format: J. Kim, K. Park, J. Shin, H. Ahn, J. Ahn, S. Lee, Y. Park. Different gene expression between breast cancer and adjacent normal breast tissue according to breast cancer subtype abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-08-19.