Abstract 3204: Association between oxidative damage and early adverse skin reactions following postoperative adjuvant radiotherapy in breast cancer patients

Abstract

Abstract Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in American women. Lumpectomy followed by radiotherapy (RT) has significantly improved survival. However, about 30% of patients develop a grade 2 or worse early or late skin reaction, pain, breast edema and poor cosmetic results that impact quality of life. Inter-individual variability in the development of RT-induced adverse reactions in normal tissue is well-documented for both acute and late effects. Therefore, identifying individuals which may have severe reactions could assist the radiation oncologist in tailoring a treatment regimen which provides adequate care with minimal undesirable effects. One of the hallmarks of radiation induced DNA damage is the oxidation of the nucleotide guanine. Repair and excretion of this modified base known as 8-hydroxydeoxyguanosine (8-OHdG) serves as a biomarker of oxidative stress and DNA damage. In an ongoing study, we investigated the urinary level of 8-OHdG (presented as ng/mg creatinine) in urine of the first 103 breast cancer patients undergoing adjuvant RT following breast conservation surgery. The normal skin toxicity at 3 weeks and at the end of treatment was assessed and associated with 8-OHdG levels. There was a significant correlation between pre- (55.8+35.2) and post-RT (55.5+37.4) urinary 8-OHdG levels (Pearson correlation coefficient=0.44; p<0.001). Within our patient population, Non-Hispanic Whites had a significantly higher 8-OHdG level (80.9+52.6) compared to Hispanic Whites (48.2+25.2, p=0.001) and Black or African Americans (43.7+20.9, p=0.008). With limited sample size, at 3 weeks of post-RT, patients with no apparent skin reaction showed a non-significantly lower pre-RT 8-OHdG (46.4+23.5) compared to patients with a grade 1 or 2 skin toxicity (57.8+37.5, p=0.18). Similar trend was also observed for post-RT 8-OHdG (45.6+20.7 vs. 57.7+40.3; p=.20). At the end of RT, patients with detectable skin toxicity had a baseline 8-OHdG level of 56.0+35.6 while patients without a skin reaction had a baseline level of 39.6+17.6. In summary, our preliminary data with limited sample size showed significant racial/ethnic differences in urinary 8-OHdG levels and promising but not significant association between 8-OHdG levels and skin toxicity grade. Larger studies are warranted to validate these interesting findings. The outcome of the ongoing study (n=1000) will target effective intervention and treatment strategies, and ultimately improve quality of life and progression-free survival in high-risk breast cancer patient populations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3204. doi:10.1158/1538-7445.AM2011-3204