Background: In breast cancer, high levels of the inflammatory cytokine interleukin-6 (IL-6) have been associated with disease-free survival and treatment resistance. Increased serum levels of IL-6 have been correlated with increased levels of NF-κβ and aromatase expression in adipose tissue. Several IL6 single nucleotide polymorphisms have been associated with breast cancer prognosis, but the impact may differ depending on tumour oestrogen receptor (ER) status. This translational study investigated the association between IL6 genotypes, ER-status, and treatment on the risk of early events among breast cancer patients.
Methods: The study included 634 25- to 99-year-old primary breast cancer patients in Sweden from 2002-2008. Genotyped IL6 single nucleotide polymorphisms rs1800797, rs1800796, rs1800795, and rs2069849 were analysed separately and as diplotypes. Disease-free survival was assessed for 567 patients. Clinical data, patient-, and tumour-characteristics were obtained from questionnaires, patient charts, population registries, and pathology reports.
Results: The median follow-up time was 5.1 years. IL6 diplotype was not associated with early events for all 567 patients, but AGCC/AGCC diplotype-carriers with ER-negative tumours had an increased risk, (adjusted Hazard Ratio (HR) = 5.91, 95% CI: 1.28-27.42). Any C-carriers (rs1800795) with ER-negative tumours had a higher risk of early events than GG-carriers with ER-negative tumours, (adjusted HR = 3.76, 95% CI: 1.05-13.43), particularly after radiotherapy (adjusted HR = 7.17, 95% CI: 1.16-32.28). Irrespective of ER-status, chemotherapy-treated Any C-carriers had a higher risk of early events than GG-carriers (adjusted HR = 3.42, 95% CI: 1.01-11.54).
Conclusions: The main finding of the present study was that IL6 genotype was strongly associated with early events among patients with ER-negative tumours, particularly among radiotherapy-treated patients, and among chemotherapy-treated patients irrespective of ER-status. The high risk for early events observed in these subgroups of patients suggests that combined information on IL6 genotype, tumour ER-status, and breast cancer treatment may represent a tool for identifying patients who require more personalised treatment.