BREAST CANCER DURING PREGNANCY AS A SPECIAL TYPE OF EARLY-ONSET BREAST CANCER: INSIGHTS INTO THE TUMOR MICROENVIRONMENT AND IMMUNE TRANSCRIPTOME

Breast cancer during pregnancy (PrBC) is a rare tumor with limited information on its immune landscape. Here, we sought to characterize the cellular composition of the tumor microenvironment (TME) and the immune transcriptome of PrBC to identify their differences from early-onset breast cancer (EOBC) in non-pregnant women. Eighty-three PrBC and 89 EOBC were selected and subjected to tumor-infiltrating lymphocytes (TILs) profiling and immunohistochemistry for CD4, CD8, forkhead box P3 (FOXP3), and programmed death-ligand 1 (PD-L1) (clone 22C3). A subset of 28 PrBC and 23 EOBC was selected for transcriptome profiling. RNA extracted from tumor (T) and corresponding normal (N) tissues was subjected to gene expression analysis using a next-generation sequencing assay (Oncomine™ Immune Response Research Assay) targeting 395 immune-related genes. A significantly lower frequency of hormone receptor (HR)-positive tumors was found in PrBC. The prevalence of low/null PD-L1 and CD8+TILs was higher in PrBC than in the controls, specifically in HR+/HER2– breast cancers. PrBC had a significantly higher risk of relapse and disease-related death, compared to EOBC. The presence of TILs and each TIL subpopulation were significantly associated with disease relapse. The death rate was higher in PrBC with CD8+ TILs. Twenty-three differentially expressed genes (DEGs) were found in the comparison between T (PrBC and EOBC), 3 (IFNA17, IFNB1, and PECAM1) upregulated and 20 downregulated. Compared to corresponding N, PrBCT had 46 upregulated and 18 downregulated genes. Four DEGs were PrBCT-specific, one (PECAM1) upregulated and 3 (CXCL1, CCL21, and HGF) downregulated. The TME and immune transcriptome of PrBC are characterized by specific patterns of TIL subpopulations and distinct gene expression patterns. Assessment of TILs and TILs subtyping in these patients might help to identify clinically relevant subsets of women with PrBC. Our findings suggest that immune regulation takes different genomic pathways in PrBC, and PrBCT has a unique immune transcriptome.