Evaluation of serum estrogen-DNA adducts as potential biomarkers for breast cancer risk

This study was conducted to determine whether the ratio of estrogen-DNA adducts to their respective metabolites and conjugates in serum differed between women with early-onset breast cancer and those with average or high risk of developing breast cancer.Serum samples from women at average risk (n = 63) or high risk (n = 80) for breast cancer (using Gail model) and women newly diagnosed with early breast cancer (n = 79) were analyzed using UPLC–MS/MS. Adduct ratios were statistically compared among the three groups, and the Area Under the Receiver Operating Characteristic Curve (AUC) was used to identify a diagnostic cut-off point.The median adduct ratio in the average-risk group was significantly lower than that of both the high-risk group and the breast cancer group (p values < 0.0001), and provided good discrimination between those at average versus high risk of breast cancer (AUC = 0.84, 95% CI 0.77–0.90). Sensitivity and specificity were maximized at an adduct ratio of 77. For women in the same age and BMI group, the odds of being at high risk for breast cancer was 8.03 (95% CI 3.46–18.7) times higher for those with a ratio of at least 77 compared to those with a ratio less than 77.The likelihood of being at high risk for breast cancer was significantly increased for those with a high adduct ratio relative to those with a low adduct ratio. These findings suggest that estrogen-DNA adducts deserve further study as potential biomarkers for risk of developing breast cancer.

► The identification of biomarkers associated with breast cancer risk is needed.
► Estrogen metabolites react with DNA to form depurinating estrogen DNA adducts.
► Depurinating estrogen-DNA adducts can initiate the cancer process.
► Validation of potential serum biomarkers aid cancer risk assessment.