In an extension of our previous investigation that examined the effects of acute STAT3/5 inhibition on system xc- in human breast cancer cells, representative subtypes of resistant breast cancer cells clonally selected through long-term treatment with the novel STAT3/5 inhibitor, SH-4-54, were assessed for changes in xCT expression and system xc- activity relative to untreated wild-type cells using functional and RNA-sequencing-based analyses. Here, STAT3 is linked to breast carcinoma.