Acute and Chronic Effects of Adjuvant Therapy on Inflammatory Markers in Breast Cancer Patients

Abstract

Background Inflammation contributes to poor behavioral, functional, and clinical outcomes in cancer survivors. We examined whether standard cancer treatments—radiation and chemotherapy—led to acute and persistent changes in circulating markers of inflammation in breast cancer patients. Methods One-hundred and ninety-two women diagnosed with early-stage breast cancer provided blood samples before and after completion of radiation and/or chemotherapy and at 6, 12, and 18-month post-treatment follow-ups. Samples were assayed for circulating inflammatory markers, including TNF-α and IL-6, downstream markers of their activity [soluble TNF receptor type II (sTNF-RII), C reactive protein (CRP)], and other inflammatory mediators (IL-8, IFN-γ). Analyses evaluated within-group changes in inflammatory markers in four treatment groups: no radiation or chemotherapy (n = 39), radiation only (n = 77), chemotherapy only (n = 18), and chemotherapy with radiation (n = 58). Results Patients treated with chemotherapy showed statistically significant increases in circulating concentrations of TNF-α, sTNF-RII, IL-6, and IFN-γ from pre- to post-treatment, with parameter estimates in standard deviation units ranging from 0.55 to 1.20. Those who received chemotherapy with radiation also showed statistically significant increases in IL-8 over this period. Statistically significant increases in TNF-α, sTNF-RII, IL-6, IFN-γ, and IL-8 persisted at 6, 12, and 18 months post-treatment among patients treated with chemotherapy and radiation (all ps < .05). Patients treated with radiation only showed a statistically significant increase in IL-8 at 18-months post-treatment; no increases in any markers were observed in patients treated with surgery only. Conclusions Chemotherapy is associated with acute increases in systemic inflammation that persist for months after treatment completion in patients who also receive radiation therapy. These increases may contribute to common behavioral symptoms and other comorbidities in cancer survivors.

Plasma levels of interleukin‐6 mediate neurocognitive performance in older breast cancer survivors: The Thinking and Living With Cancer study

“…We found that IL-6, IL-10, and TNF-α had a direct relationship with cognition in survivors and controls, findings that parallel prior work by others. 13,[18][19][20][22][23][24][25]39,40 The modest but nonsignificant mediation effect of IL-10, which has regulatory anti-inflammatory and B cell stimulatory activity, may reflect the dynamic nature of its secondary responses to increased proinflammatory markers. 41 IFN-γ, which is produced during immune activation and antiviral responses, and IL-8, which is a chemoattractant for neutrophils, were unrelated to cognition.…”

“…This will be important to examine further, because others have found that radiotherapy and/or chemotherapy induce cellular damage that increases peripheral inflammation and cognitive problems and that HER2-positive cancers are associated with cognitive problems even before treatment. 19,24,38 Fifth, because we added blood collection to an already established cohort, not all survivors had plasma data before systemic therapy.…”

“…We evaluated five immune markers (interleukin‐6 [IL‐6], IL‐8, IL‐10, tumor necrosis factor α [TNF‐α], and interferon γ [IFN‐γ]) previously associated with cognition in cancer survivors 13,18–20,22–25 . Marker plasma levels were determined using an electrochemiluminescent immunoassay (MesoScale Discovery Custom Human Cytokine Proinflammatory Panel, Rockville, Maryland) 26 .…”

“…previously associated with cognition in cancer survivors. 13,[18][19][20][22][23][24][25] Marker plasma levels were determined using an electrochemiluminescent immunoassay (MesoScale Discovery Custom Human Cytokine Proinflammatory Panel, Rockville, Maryland). 26 Assays were performed in duplicate at a 2-fold sample dilution with an extended eight-point standard curve of serial 3-fold dilutions.…”

Sustained Mild Inflammation in Cancer Survivors: Where to from Here?

“…The data are part of a larger longitudinal study investigating cancer-related fatigue in women with stage 0-IIIA breast cancer assessed prior to starting adjuvant or neoadjuvant treatment, approximately 2 weeks after completion of radiation and/or chemotherapy in those who received it, and 6, 12, and 18 months later. Six pro-inflammatory markers were assessed in plasma (tumor necrosis factor–α, interleukin [IL]–6, IL-8, soluble tumor necrosis factor receptor type II, interferon-γ, and C-reactive protein [CRP]) in 192 (71%) of the RISE participants, with the primary aim of evaluating the impact of radiotherapy and chemotherapy on the inflammatory markers ( 6 ). When considered broadly, the findings support the contention that inflammation can be sustained above baseline levels for months to years following cancer treatment despite tending to decline posttreatment.…”