Excessive glutathione intake contributes to chemotherapy resistance in breast cancer: a propensity score matching analysis.

BACKGROUND

We aim to explore the impact of excessive glutathione (GSH) intake on chemotherapy sensitivity in breast cancer.

METHODS

Clinicopathological data were collected from 460 breast cancer patients who underwent adjuvant chemotherapy from January 2016 to December 2019 from Zhengzhou University People's Hospital. The clinicopathological characteristics following GSH treatment were collected and compared with those in Non-GSH group after 1:2 propensity score matching (PSM). Intracellular GSH levels and the expression of antioxidant enzymes (NRF2, GPX4 and SOD1) were evaluated in tumor tissues in 51 patients receiving neoadjuvant chemotherapy.

RESULTS

The recurrence rate after adjuvant chemotherapy was significantly higher in the GSH group (n = 28, 31.8%) than that in the Non-GSH group (n = 39, 22.2%; P = 0.010). Additionally, patients in the HGSH group (high GSH intake, ≥ 16 days) exhibited an elevated recurrence rate compared to that in the LGSH group (low GSH intake, < 16 days) (n = 15 (46.8%) vs. n = 52 (22.4%); P = 0.003). Cox regression revealed that High GSH intake, Ki67 ≥ 30%, Triple negative and Lymphovascular invasion were independent risk factors of progression after adjuvant chemotherapy. Among patients receiving neoadjuvant chemotherapy, intracellular GSH levels and the expression levels of antioxidant enzymes (NRF2, GPX4 and SOD1) in the resistant patients were substantially higher (P < 0.001).

CONCLUSIONS

Excessive GSH intake may contribute to chemotherapy resistance in breast cancer, and the levels of intracellular GSH and antioxidant enzymes are elevated in resistant patients after neoadjuvant chemotherapy, indicating that the standardization of GSH intake may assist in reducing chemotherapy resistance.