Triple-negative breast cancer tumors are thought to be more immunogenic than other breast cancer subtypes, such as luminal A/B or human epidermal growth factor receptor 2-positive (HER2+) tumors. Among all breast cancers, tumors appear more commonly in the upper outer quadrant. However, it is not clear whether expression of immune response genes vary with tumor location among the different subtypes. Researchers assessed gene expression associated with immune response pathways to identify potential treatment targets and presented the findings at the San Antonio Breast Cancer Symposium on December 6, 2018.

Using the Cancer Genome Atlas dataset to identify 918 breast cancer tumor samples, the researchers compared RNA sequencing gene expression based on molecular subtypes and anatomic locations of biopsies at the right side, left side, lower inner quadrant, lower outer quadrant, upper inner quadrant, or upper outer quadrant. They then selected genes with significantly different expression for survival analysis.

Triple-negative breast cancer tumors from lower outer quadrant and lower inner quadrant had significantly higher CD8B messenger RNA (mRNA) expression compared to luminal A/B and HER2+ tumors from same locations. However, at other triple-negative breast cancer tumors sites, CD8B mRNA was not significantly higher compared to luminal A/B and HER2+ tumors. Pathways and genes associated with cytotoxic T cell function remained significantly different between the sites for triple-negative breast cancer compared to other subtypes. The metastasis suppressor gene CD82 was significantly higher in triple-negative breast cancer samples from the right side, lower outer quadrant, lower inner quadrant, and upper inner quadrant. However, the gene was not significantly expressed in the upper outer region, “where tumors are prevalent,” the researchers noted.

According to results of an immune pathway analysis, genes involved in the antigen activates B cell receptor pathway (p < 0.05) were associated with overall survival (OS) in right- and left-sided luminal A/B and HER2+ tumors and right-sided triple-negative breast cancer tumors. Genes from pathways involved in immune-regulatory interactions between lymphoid and non-lymphoid cells were associated with OS in lower outer quadrant and upper outer quadrant tumors in luminal A/B and HER2 tumors, as well as in right-sided tumors in triple-negative breast cancer (p < 0.05).