ERBB2 and breast neoplasm: However, hypoxia has been shown to inhibit NHE1 activity22 and recent interrogation of The Cancer Genome Atlas (TCGA) for NHE1 gene expression in primary breast tumor samples has shown that NHE1 gene expression is significantly lower in tumors of the basal subtype compared to luminal and human epidermal growth factor receptor 2-positive (HER2+) subtypes,23 suggesting the importance of pH regulatory proteins such as CAIX in contributing to extracellular acidosis in hypoxia.