Role of inflammation and oxidative stress in post-menopausal oestrogen-dependent breast cancer

Abstract

Weight gain and obesity are among the most important risk factors for post-menopausal oestrogen-dependent breast cancer (EDBC). Weight gain is associated with oxidative stress, which in turn promotes breast cancer progression. We carried out a prospective study in 216 consecutive post-menopausal breast cancer patients aiming to examine the correlations between traditional prognostic factors (tumour size, T, nodal, N, grading, G, and metastasis status, M), and body mass index (BMI), leptin, pro-inflammatory cytokines (Interleukin, IL,-6 and tumour necrosis factor-alpha, TNF-α), and oxidative stress (reactive oxygen species, ROS, glutathione peroxidase, GPx, superoxide dismutase, SOD) among patients with oestrogen receptor (ER)+ and ER- breast cancers. Distribution of T, N and M categories did not differ between ER+ and ER- breast cancer patients. ER- patients showed a higher incidence of G3 tumours. Weight, BMI, leptin, IL-6 and ROS were higher in ER+ compared with ER- patients. Among ER+ patients, BMI, leptin, IL-6 and ROS correlated with T and M. Leptin, IL-6 and ROS were positively correlated also with N. Among ER- patients, BMI and leptin did not correlate with any of prognostic parameters, whereas a positive correlation between IL-6, ROS and M was found. Multivariate regression analysis showed that BMI, leptin, IL-6 and ROS were predictive for T, N and M in ER+ patients. Weight gain, inflammation and oxidative stress are involved in EDBC prognosis. Their modulation through antidiabetic, anti-inflammatory and antioxidants drugs combined with endocrine therapy may constitute a targeted approach in post-menopausal EDBC.

Keywords: Interleukin-6; adiposity; leptin; oestrogen-dependent breast cancer; oxidative stress.

Fig. 1

Serum levels of IL-6, TNF-α and leptin in post-menopausal breast cancer patients according to ER status. Patients with ER+ breast cancer showed significantly higher levels of IL-6 and leptin in comparison with ER− breast cancer patients. The box plots in the figure represent columns of data as boxes whose extents indicate the 25th and 75th percentiles of the column. The line inside the box represents the median. + marks the value of the mean. Capped bars indicate the minimum and maximum value observed. IL, Interleukin; TNF, Tumour necrosis Factor; ER, oestrogen receptor.

Fig. 2

Blood levels of oxidative stress parameters (ROS, GPx and SOD) in post-menopausal breast cancer patients according to ER status. Patients with ER+ breast cancer showed significantly higher levels of ROS in comparison with ER− breast cancer patients. The box plots in the figure represent columns of data as boxes whose extents indicate the 25th and 75th percentiles of the column. The line inside the box represents the median. + marks the value of the mean. Capped bars indicate the minimum and maximum value observed. ROS, reactive oxygen species; GPx, glutathione peroxidase; SOD, superoxide dismutase; ER, oestrogen receptor.