Urinary biomarkers of oxidative stress and breast cancer survival.

Abstract

Systemic oxidative stress has been implicated in the pathogenesis and progression of many chronic diseases, including breast cancer. No studies have investigated F2-isoprostanes (F2-IsoPs), valid biomarkers of systemic oxidative stress, in association with breast cancer prognosis. We conducted a nested case-control study in a prospective breast cancer survivor cohort to investigate systemic oxidative stress and survival. Urinary levels of F2-IsoPs and its major urinary metabolite (2,3-dinor-5,6-dihydro-15-F2t-IsoP, F2-IsoP-M) were measured post-cancer treatment using gas chromatography/negative ion chemical ionization mass spectrometry for 57 deceased breast cancer patients (cases) and 103 surviving patients (controls) matched 1:2 on age at diagnosis, stage, and diagnosis year. Odds ratios (ORs) and 95 % confidence intervals (CIs) were derived from conditional logistic regression models. In unadjusted models, elevated F2-IsoP levels categorized based on the median value [≥1.73; <1.73 (reference)] were nonsignificantly inversely associated with mortality (OR 0.51, 95 % CI 0.24-1.10). After adjustment for potential confounders, elevated F2-IsoP levels were significantly associated with mortality (OR 0.36, 95 % CI 0.14-0.96). The inverse association was marginally significant when F2-IsoP was categorized based on tertiles (p trend = 0.08). In contrast, elevated F2-IsoP-M levels, categorized based on the median level [≥0.91; < 0.91(reference)], were associated with a statistically nonsignificant increased risk of mortality in both unadjusted and adjusted models (adjusted OR 1.39, 95 % CI 0.62-3.09). Results suggest a role for oxidative stress biomarkers in breast cancer survival; however, as this is the first study to date, additional larger studies are needed.