Low Plasma IL-8 Levels During Chemotherapy Are Predictive of Excellent Long-Term Survival in Metastatic Breast Cancer

Abstract

Plasma interleukin (IL)-8 levels were monitored in 58 patients with metastatic breast cancer before and during first-line chemotherapy, and changes in the IL-8 levels were correlated with patient survival data. Monitoring plasma IL-8 levels before and during chemotherapy identifies patients with excellent prognosis whose IL-8 levels stay constantly below 16.6 pg/mL. Background: Interleukin (IL)-8 is a proinflammatory cytokine, and high levels of IL-8 are associated with poor prognosis in many malignancies. The objective of this study was to explore the clinical benefit of monitoring plasma IL-8 levels during breast cancer chemotherapy. Patients and Methods: We conducted an exploratory analysis of several circulating proteins, including IL-8, in the plasma. Plasma samples were obtained from 58 metastatic breast cancer patients who took part in a prospective phase 2 first-line bevacizumab chemotherapy trial. Samples were analyzed before therapy, after 6 weeks and 6 months of treatment, and at the final study visit. On the basis of a trajectory analysis of the plasma IL-8 levels, the patients were divided into 3 trajectory groups. Results: Plasma IL-8, IL-6, IL-18, matrix metalloproteinase (MMP)-2, MMP-9, YKL-40, resistin, and high-mobility group box 1 (HMGB1) concentrations were measured, and the most pronounced predictor of patient survival was IL-8. On the basis of the trajectory analysis of the IL-8 levels, the majority of patients (n ¼ 35, 60%) belonged to trajectory group 1, and these patients had significantly lower IL-8 levels before and during the entire chemotherapy treatment period than did the patients in the other groups. Trajectory group 1 patients had significantly better overall survival compared to patients in trajectory group 2 (n ¼ 17; age-adjusted HR ¼ 2.45; 95% confidence interval, 1.21-5.97; P ¼ .012) and 3 (n ¼ 6; age-adjusted HR ¼ 8.65; 95% confidence interval, 3.16-23.7; P < .001). Conclusion: Low IL-8 levels during chemotherapy treatment might help identify patients with prolonged survival.

Circulating cytokines associated with clinical outcomes in advanced non‐small cell lung cancer patients who received chemoimmunotherapy

“…IL-8 has been observed to be associated with worse disease prognosis in pancreatic cancer, ovarian cancer, breast cancer and NSCLC. [17][18][19][20] Our results contribute to the literature in the era of chemoimmunotherapy.…”

Doxorubicin‐induced senescence promotes stemness and tumorigenicity in EpCAM−/CD133− nonstem cell population in hepatocellular carcinoma cell line, HuH‐7

“…Interleukin-8 (IL-8) is a known mediator of inflammation and carcinogenesis through its activities related to stem cells, angiogenesis, and metastasis [10,38,68]. High IL-8 levels have been associated with poor prognosis in many malignancies including HCC [10,[68][69][70][71]. Furthermore, induction of IL-8 by Dox was shown to increase the proportion of stem cells in HCC cell lines, while inhibiting the IL-8 signaling pathway decreases stem cell population and attenuates drug resistance [68].…”

“…Recently, Eggert et al (2016) showed that while SASP of senescent hepatocytes Interleukin-8 (IL-8) is a known mediator of inflammation and carcinogenesis through its activities related to stem cells, angiogenesis, and metastasis [10,38,68]. High IL-8 levels have been associated with poor prognosis in many malignancies including HCC [10,[68][69][70][71].Furthermore, induction of IL-8 by Dox was shown to increase the proportion of stem cells in HCC cell lines, while inhibiting the IL-8 signaling pathway decreases stem cell population and attenuates drug resistance [68]. Our findings also suggest that IL8 might mediate the bridge between senescence and stemness in HCC and can be an important mediator of the cancer-promoting properties of senescent tumor cells.…”

High Mobility Group Box 1 in Human Cancer

“…In a separate study, the prognostic significance of plasma HMGB1, IL-6, IL-8, IL-18, MMP-2, MMP-9, glycoprotein YKL-40 and resistin were investigated in 58 metastatic breast cancer patients. In this study, only low levels of IL-8 were associated with increased overall survival, while HMGB1 was not significant [ 188 ].…”