Whereas the cytosolic and mitochondrial carbonic anhydrases show no (CA1, CA2, CA3, CA5A, CA5B, CA7) or only minimal (CA13) regulation between breast cancers of different malignancy grades, the secreted (CA6) and extracellular-facing, membrane-tethered (CA4, CA9, CA12, CA14) carbonic anhydrases are markedly altered in expression between high and low malignancy grade breast cancer (Fig. 1D and Additional file 1: Table S4). Here, CA4 is linked to breast cancer.