Prognostic Impact of Stimulator of Interferon Genes Expression in Triple Negative Breast Cancer

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Triple negative breast cancer (TNBC) patients with poor response to neoadjuvant chemotherapy (NAC) exhibit worse survival rates.
• The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, an innate immune response, is implicated in TNBC.
• The cGAS-STING pathway is activated by DNA damage and represents a potential therapeutic target in TNBC.

Purpose of the Study:

• To investigate the association between STING expression and immune profiles in TNBC.
• To evaluate the prognostic significance of STING expression in TNBC patients undergoing NAC.
• To explore STING as a potential therapeutic target for TNBC.

Main Methods:

• Retrospective analysis of 91 TNBC patients who received NAC and surgery.
• Immunohistochemistry was used to assess STING, cGAS, CD8, PD-L1 expression, and tumor-infiltrating lymphocytes (TILs).
• Specimens were analyzed pre-treatment and post-treatment (at surgery) to evaluate sustained STING expression.

Main Results:

• High baseline STING expression showed a marginal correlation with TILs but not with CD8+ cells or PD-L1.
• Patients with sustained high STING expression (pre- and post-NAC) had significantly poorer distant recurrence-free survival and breast cancer-specific survival.
• The association between sustained high STING expression and poor prognosis was independent of nodal status, lymphatic invasion, and therapeutic effects.

Conclusions:

• Sustained high STING expression in TNBC post-NAC is associated with a poor prognosis.
• The STING pathway represents a promising therapeutic target for developing new treatment strategies in TNBC.
• Further research into targeting the STING pathway could improve outcomes for TNBC patients.