Breast cancer occurring during pregnancy of Luminal A type overexpressed CXCL13

Abstract

Background Breast cancer during pregnancy and lactation occurs in 2.6% of female patients aged < 45 years, and its incidence has been increasing. The pathogenesis and genomic profiles of pregnancy-associated breast cancer (PABC) remain unclear. We analyzed patients with breast cancer that occurred during pregnancy (PrBC) and compared the findings with those of patients with breast cancer that did not occur during pregnancy (non-PrBC). Methods We performed gene expression analyses (using microarray and qRT-PCR) of PrBC (8 and 22 samples, respectively) and non-PrBC (8 and 24 samples, respectively) groups, which were matched for age, hormone receptor expression, and HER2 expression. Results Microarray analysis showed that 355 genes were upregulated and 151 genes were downregulated in the luminal type PrBC group compared to those in the non-PrBC group. Chemokine, C-X-C motif chemokine ligand 13 (CXCL13) gene was the most upregulated in the PrBC group compared to that in the non-PrBC group (log2 fold-change = 101.2), especially in the luminal A-type cells (p = 0.016). This result was corroborated by the qRT-PCR analysis of microdissected cancer cells, which was conducted using formalin-fixed paraffin-embedded (FFPE) samples (p < 0.001). A negative correlation was observed between CXCL13 and estrogen receptor 1 (ESR1) mRNA expression levels in luminal A-type breast carcinoma (τ = -0.109; p < 0.001). Conclusion CXCL13, a chemokine that regulates the function of immune cells, was significantly overexpressed in PrBC cells. The expression levels of CXCL13 and estrogen receptor (ER) were inversely correlated.