Mixed molecular subtypes coexist in estrogen receptor heterogenous primary breast cancers

We performed spatial transcriptomic profiling of ER-negative, ER-low, and ER-high tumor cell regions of breast cancers that were 10-60% ER positive on routine immunohistochemistry using the GeoMxTM platform targeting 18,676 genes.

We found that Luminal A and B molecular subtypes were intermixed in these tumors but there were no Basal-like cell populations. The ER-negative tumor regions were Luminal B-like and showed significantly lower expression of ESR1 and endocrine therapy sensitivity gene signatures but higher expression of inflammation and immune related genes, and also had higher recurrence scores indicating an endocrine-resistant but more chemotherapy sensitive phenotype.