Résumé
Simple Summary Certain nutrients are needed by cancers to grow. Some breast cancers need the nutrient glutamine to grow and without it they don't grow as quickly. In this study, we wanted to know the role of an enzyme, glutaminase, which is a substance produced by the body that breaks down glutamine so it can be used by cancers to grow. This enzyme occurs as two different types but we don't know what their roles are in breast cancer. We therefore looked at the two types of enzyme in over 7000 breast cancers. We found that patients with high amounts of enzyme in early forms of breast cancer died earlier. Therefore, this enzyme has an important role in breast cancer and could be used to identify cancers which will get worse. We also think that using a drug to stop this enzyme will stop cancers growing. More studies are needed to confirm this. The glutamine metabolism has a key role in the regulation of uncontrolled tumour growth. This study aimed to evaluate the expression and prognostic significance of glutaminase in luminal breast cancer (BC). The glutaminase isoforms (GLS/GLS2) were assessed at genomic/transcriptomic levels, using METABRIC (n = 1398) and GeneMiner datasets (n = 4712), and protein using immunohistochemistry in well-characterised cohorts of Oestrogen receptor-positive/HER2-negative BC patients: ductal carcinoma in situ (DCIS; n = 206) and invasive breast cancer (IBC; n = 717). Glutaminase expression was associated with clinicopathological features, patient outcome and glutamine-metabolism-related genes. In DCIS, GLS alone and GLS+/GLS2- expression were risk factors for shorter local recurrence-free interval (p < 0.0001 and p = 0.001, respectively) and remained prognostic factors independent of tumour size, grade and comedo necrosis (p = 0.0008 and p = 0.003, respectively). In IBC, GLS gene copy number gain with high mRNA expression was associated with poor patient outcome (p = 0.011), whereas high GLS2 protein was predictive of a longer disease-free survival (p = 0.006). Glutaminase plays a role in the biological function of luminal BC, particularly GLS in the early non-invasive stage, which could be used as a potential biomarker to predict disease progression and a target for inhibition. Further validation is required to confirm these observations, and functional assessments are needed to explore their specific roles.