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Breast cancer (BC) is a heterogeneous disease characterised by variant biology, metabolic activity and patient outcome. This study aimed to evaluate the biological and prognostic value of the membrane solute carrier, SLC3A2 in BC with emphasis on the intrinsic molecular subtypes. SLC3A2 was assessed at the genomic level, using METABRIC data (n = 1980), and at the proteomic level, using immunohistochemistry on tissue microarray (TMA) sections constructed from a large well-characterised primary BC cohort (n = 2500). SLC3A2 expression was correlated with clinicopathological parameters, molecular subtypes and patient outcome. SLC3A2 mRNA and protein expression were strongly correlated with higher tumour grade and poor Nottingham prognostic index (NPI). High expression of SLC3A2 was observed in triple-negative (TN), HER2+ and ER+ high-proliferation subtypes. SLC3A2 mRNA and protein expression were significantly associated with the expression of c-MYC in all BC subtypes (p &lt; 0.001). High expression of SLC3A2 protein was associated with poor patient outcome (p &lt; 0.001), but only in the ER+ high-proliferation (p = 0.01) and TN (p = 0.04) subtypes. In multivariate analysis SLC3A2 protein was an independent risk factor for shorter BC-specific survival (p &lt; 0.001). SLC3A2 appears to play a role in the aggressive BC subtypes driven by MYC and could act as a potential prognostic marker. Functional assessment is necessary to reveal its potential therapeutic value in the different BC subtypes.

The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes