Triple-negative breast cancer (TNBC) and basal-like breast cancer (BLBC) are breast cancer subtypes with an especially poor prognosis. 8-Hydroxydeoxyguanosine (8-OHdG) is a widely used marker of oxidative stress and the redox-state-regulating enzymes peroxiredoxins (PRDXs) are efficient at depressing excessive reactive oxygen species. NF-E2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) are redox-sensitive transcription factors that regulate PRDX expression. This is the first study to assess oxidative stress and or cell redox state-regulating enzymes in TNBC and BLBC.

We assessed immunohistochemical expression of 8-OHdG, Nrf2, Keap1, PRDX III and PRDX IV in 79 women with invasive ductal breast carcinomas. Of these tumors, 37 represented TNBC (grade II-III tumors with total lack of ER, PR and human epidermal growth factor receptor 2 [HER2] expression). Control cases (n=42) were ER-positive, PR-positive and HER2-negative. Of the 37 TNBCs, 31 had BLBC phenotype (TNBC with expression of cytokeratin 5/6 or epidermal growth factor receptor 1).

Patients with TNBC had worse breast cancer-specific survival (BCSS) than the control group (p=0.015). Expression of 8-OHdG was significantly lower in TNBC than in the non-TNBC group (p<0.005). 8-OHdG immunostaining was associated with better BCSS (p=0.01), small tumor size (p<0.0001) and low grade (p<0.0005). Keap1 overexpression was observed in the TNBC cohort (p=0.001) and Keap1-positive patients had worse BCSS than Keap1-negative women (p=0.014). PRDX IV was overexpressed in the TNBC vs. the non-TNBC group (p=0.022).

Cellular redox state markers may be promising targets when elucidating the pathogenesis of TNBC.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.