Profiling of Protein Adducts of Estrogen Quinones in 5-Year Survivors of Breast Cancer Without Recurrence

Abstract

Aims The aim of this study was to simultaneously analyze estrogen quinone-derived adducts, including 17β-estradiol-2,3-quinone (E2-2,3-Q) and 17β-estradiol-3,4-quinone (E2-3,4-Q), in human albumin (Alb) and hemoglobin (Hb) derived from breast cancer patients with five-year postoperative treatment without recurrence in Taiwan and to evaluate the treatment-related effects on the production of these adducts. Settings and Design Cohort Methods and Material: Blood samples derived from breast cancer 5-year survivors without recurrence were collected. Albumin and hemoglobin adducts of E2-3,4-Q and E2-2,3-Q were analyzed to evaluate the degree of disposition of estrogen to quinones and to compare these adduct levels with those in patients before treatment. Statistical Analysis All data are expressed as mean ± standard deviation of three determinations. We used Student’s t-test to examine subgroups. Data were transformed to the natural logarithm and tested for normal distribution for parametric analyses. Linear correlations were investigated between individual adduct levels by simple regression. Statistical analysis was performed using the SPSS Statistics 20.0. Results Result confirmed that logged levels of E2-2,3-Q-derived adducts correlated significantly with those of E2-3,4-Q-derived adducts (correlation coefficient r=.336-.624). Mean levels of E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb in 5-year survivors were reduced by 60-70% when compared to those in the breast cancer patients with less than one year of diagnosis/preoperative treatment (P<.001). Conclusions Our findings add support to the theme that hormonal therapy including aromatase inhibitors and Tamoxifen may dramatically reduce burden of estrogen quinones. We hypothesize that combination of treatment-related effects and environmental factors may modulate estrogen homeostasis and diminish the production of estrogen quinones in breast cancer patients.