Low 5-hydroxymethylcytosine level is an independent predictor of high histological grade in locally advanced breast cancer

Background: Breast cancer is a major cause of cancer mortality worldwide. In Mexico, most cases are diagnosed in locally advanced stages, which is associated with a poor prognosis. Recent studies have suggested that 5-hydroxymethylcytosine (5hmC) levels could be a prognostic marker in cancer. However, the role of 5hmC as a predictor of histopathological alterations in breast cancer have not been fully studied. Results: We evaluated samples from patients with breast cancer (N=141), with a mean age of 50.12 yrs. (standard deviation [SD]: 9,54 yrs.), tumors showed a mean diameter of 6.53 cm (SD: 3.06 cm) at diagnosis, most of the patients showed overweight or obesity (77.3%) and most of them were locally advanced stage (n=111). A statistically significant and negative correlation between 5hmC levels and age in ER/PR-negative tumors ( = -0.028, 95% confidence interval [95%CI]: -0.045, -0.010, p-value = 0.005) and in triple negative tumors ( = -0.023, 95%CI: -0.044, -0.001, p-value = 0.046) was observed using mixed effects linear models. We also observed a negative correlation between 5hmC levels and an increased levels of cell proliferation markers, including Ki67 (r = -0.16, p-value < 0.01) and minichromosome maintenance complex component 2 [MCM2] (r = -0.21, p-value = 0.03). Finally, and using mixed effects models, we determined that the 5hmC level was an independent predictor of advanced histological grade in locally advanced breast cancer patients ( = -0.077, 95%CI -0.142, -0.011, p = 0.022). We did not observe differences associated with complete pathological response or free-relapse survival according to 5hmC level. Conclusions: This study suggests that low 5hmC may serve as potential marker of adverse histopathological characteristics in locally advanced breast cancer patients, highlighting its potential as a useful clinical biomarker.