Purpose: 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.
Methods: 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.
Results: 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).
Conclusion: 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.