Abstract
Systemic inflammation is believed to contribute to the distant recurrence of breast cancer. We evaluated serum samples obtained at diagnosis from 249 case:control pairs with stage II-III Her2-negative breast cancer with or without subsequent distant recurrence. Conditional logistic regression analysis, with models fit via maximum likelihood, were used to estimate hazard ratios (HRs) and test for associations of cytokines with distant recurrence risk. The only biomarker associated with a significantly increased distant recurrence risk when adjusted for multiple testing was the proinflammatory cytokine IL-6 (HR 1.37, 95% confidence intervals [CI] 1.15, 1.65, p = 0.0006). This prospective-retrospective study provides evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk.
Highlights
Inflammation is a normal physiologic response to injury, including cancer[1], and plays a key role in contributing to cancer progression[2,3]
We evaluated the association between cytokine levels and distant recurrence in 249 case:control pairs (498 patients) after primary surgery and before systemic adjuvant chemotherapy, and in 17 case:control pairs (34 patients) about 5 years after diagnosis who were without clinical evidence of recurrence
We performed a case:control study including a total of 532 patients with high-risk stage II–III HER2negative breast cancer to determine whether one or more serum cytokine levels at diagnosis, or 5 years after diagnosis when cancerfree, was associated with distant breast cancer recurrence despite surgery and adjuvant chemotherapy
Summary
Inflammation is a normal physiologic response to injury, including cancer[1], and plays a key role in contributing to cancer progression[2,3]. Inflammation facilitates cancer progression, no studies have evaluated the association between specific cytokines and recurrence of breast cancer. Prior studies have indicated that elevated C-reactive protein (CRP) and serum amyloid A (SAA) are associated with an increased risk of breast cancer recurrence[5]. CRP and SAA are nonspecific, acute-phase hepatic proteins secreted in response to cytokines, providing indirect evidence that cytokines may be contributing to breast cancer recurrence. In order to determine which specific cytokines might be mediating this effect, we evaluated the association between distant recurrence of breast cancer and serum levels of 36 human cytokines and chemokines involved in chemotaxis, angiogenesis, and immune system regulation, including effector CD4 + Th1/Th2 and Th17 T cells. We evaluated the association between cytokine levels and distant recurrence in 249 case:control pairs (498 patients) after primary surgery and before systemic adjuvant chemotherapy, and in 17 case:control pairs (34 patients) about 5 years after diagnosis who were without clinical evidence of recurrence
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