Abstract 119: Urinary biomarkers of oxidative stress and breast cancer survival among Chinese breast cancer survivors.

Abstract

Abstract Background: Systemic oxidative stress has been implicated in the pathogenesis and progression of many chronic diseases, including breast cancer. To our knowledge, no study has investigated the association of biomarkers of systemic oxidative stress after cancer treatment and breast cancer prognosis. Methods: We conducted a pilot study to investigate the association of systemic oxidative stress after primary cancer treatment with mortality in a nested case-control study in the Shanghai Breast Cancer Survival Study (SBCSS). Urinary levels of 15-F(2t)-isoprostane (15-F(2t)-IsoP) and one of its major metabolites (2,3-dinor-5,6-dihydro-15-F(2t)-IsoP (15-F(2t)-IsoP-M)), two well-studied biomarkers of systemic oxidative stress, were measured using gas chromatography/negative ion chemical ionization mass spectrometry for 57 deceased breast cancer patients (cases; 88% due to breast cancer) and 103 matched surviving breast cancer patients (controls) in the SBCSS with available post-cancer treatment urinary samples. Cases and controls were aged 26-70 years and were matched approximately 1:2 on age at diagnosis (+/- 1 year), stage (I-III), and year of diagnosis (2003-2004). Biomarkers were adjusted for creatinine concentrations and expressed as ng/mg of creatinine. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were derived from conditional logistic regression models, conditioned on age, stage, and year of diagnosis. Results: Elevated 15-F(2t)-IsoP levels, categorized based on the median level (≥1.73;<1.73(reference)), were inversely associated with mortality (adjusted OR = 0.36, 95% CI: 0.14-0.96) after adjustment for known clinical prognostic factors (including cancer treatment and tumor characteristics), body mass index, vitamin supplement use, and weeks between breast cancer diagnosis and urine collection. The inverse association was marginally significant when 15-F(2t)-IsoP was categorized based on tertiles (p for trend = 0.08). In contrast, elevated 15-F(2t)-IsoPM levels, categorized based on the median level (≥0.91;<0.91 (reference)), were associated with a statistically non-significant increased risk of mortality (adjusted OR = 1.39, 95% CI: 0.62-3.09). Conclusion: These preliminary results suggest differing associations for 15-F(2t)-IsoP and 15-F(2t)-IsoPM with mortality among breast cancer survivors. To our knowledge, this is the first study to investigate the association between 15-F(2t)-IsoP or 15-F(2t)-IsoP-M levels and breast cancer survival. Results from this pilot study require conformation in future larger studies. Citation Format: Sarah J. Nechuta, Qiuyin Cai, Ying Zheng, Ginger L. Milne, Hui Cai, Qi Dai, Gong Yang, Wei Zheng, Wei Lu, Xiao Ou Shu. Urinary biomarkers of oxidative stress and breast cancer survival among Chinese breast cancer survivors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 119. doi:10.1158/1538-7445.AM2013-119