Serum Kyn and tumoral IDO1 expression are lower in ER-positive than ER-negative breast cancer patients. (A) Sera obtained before initial surgery showed significantly lower Kyn concentrations in untreated ER-positive (n = 30) compared with untreated ER-negative breast cancer patients (n = 16, Student's t-test **p < 0.01). (B) In line, IDO1 mRNA normalized to GAPDH (Student's t-test *p < 0.05) and (C) IDO1 protein expression were higher in ER-negative (n = 6) than ER-positive (n = 9) frozen breast cancer samples from distinct patients. (D) TCGA data of breast invasive carcinoma confirm decreased IDO1 expression in ER-positive compared with ER-negative breast cancer tissue (ER(+) n = 343, ER(−) n = 99, Mann–Whitney U test ***p < 0.001). (E) Reduced IDO1 mRNA expression is observed in the ER-positive luminal compared with the mainly ER-negative Her-2 enriched and basal-like intrinsic breast cancer subtypes based on PAM50 classification, (basal-like n = 141, Her2-enriched n = 67, luminal A n = 423, luminal B n = 192). (F) In accordance with a decrease in IDO1 expression a model of Trp metabolism based on TCGA expression data of breast invasive carcinoma predicted lower Kyn concentrations in human ER-positive compared with ER-negative breast cancer (ER(+) n = 311, ER(−) n = 103, ***p < 0.001). Box plots represent the medians and the 75% and 25% percentiles. Whiskers extend to min and max values.