Abstract P2-11-14: Pathology AI features and immune biomarkers of postpartum involution: Implications for postpartum breast cancer

Abstract

Abstract Breast cancer risk is increased in parous women in the period following childbirth, peaking at five years. After weaning or in the absence of lactation, the breast undergoes postpartum involution (PPI), a process characterized by epithelial cell death and tissue remodeling that returns the mammary gland to a baseline state, and has previously been associated with increased inflammation and breast cancer development and progression in preclinical models. Features of PPI and determinants of related inflammation have been incompletely characterized among women. In this study, we performed visual and AI analysis of 725 digitized H&E images of normal breast tissues donated to the Komen Tissue Bank (KTB) by parous and nulliparous women ≤45 years, and further investigated the immune microenvironment in specimens from 23 women (also from KTB, 13 parous, 10 nulliparous) using NanoString RNA immuno oncology (IO) 360 panels and immune protein biomarkers by NanoString GeoMx Digital Spatial Profiling (DSP). We found that recently parous women (≤5 years of a last birth) had higher numbers of terminal duct lobular units (TDLUs), immune cells, and plasma cells as compared with nulliparous women, and that beyond 5 years of a last birth, TDLU numbers were still higher in parous women, but the immune and plasma cell content of the breast of parous and nulliparous women were not significantly different. Our gene expression analysis revealed differential expression of genes that clustered according to parity status, with interferon stimulated genes; STAT1 and IFITM1, and interferon alpha receptor 1 (IFNAR1), and MHC class II genes (HLA-DMA, HLA-DPA,HLA-DPB1, and HLA-DRA) elevated in parous women. Our DSP analysis revealed that immune biomarkers with immunosuppressive functions, including ARG1, VISTA, CTLA-4, and CD68 were significantly higher in parous women as compared with nulliparous women. Breast tissues of parous women show lobular expansion and alterations in immune cell components compared with nulliparous tissues. Further research is needed to assess how these alterations may impact risk. Citation Format: Joshua Were Ogony, Thomas De Bel, Derek Radisky, Jeroen VanderLaak, Mark Sherman. Pathology AI features and immune biomarkers of postpartum involution: Implications for postpartum breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-11-14.