Circulating Cytokines in Metastatic Breast Cancer Patients Select Different Prognostic Groups and Patients Who Might Benefit from Treatment beyond Progression

Abstract

Cancer induces immune suppression to overcome its recognition and eradication by the immune system. Cytokines are messengers able to modulate immune response or suppression. There is great interest in the evaluation of their changes during treatment in order to identify their relationship with clinical outcome. We evaluated 18 cytokines in breast cancer patients treated with eribulin before starting treatment (T0) and after four courses of therapy (T1). Longitudinal modifications were considered and cytokine clusters through PCA and HCPC correlated to patients’ outcomes were identified. Forty-one metastatic breast cancer patients and fifteen healthy volunteers were included. After clustering, we identified at T0 six patient clusters with different risk of relapse and death. At T1, only four clusters were identified, and three of them accounted for thirty-eight of forty-one patients, suggesting a possible role of treatment in reducing heterogeneity. The cluster with the best survival at T1 was characterized by low levels of IL-4, IL-6, IL-8, IL-10, CCL-2, CCL-4, and TGF-β. The cluster showing the worst survival encompassed high levels of IL-4, IL-6, IL-8, IL-10, CCL-2, and IFN-γ. A subgroup of patients with short progression-free survival (PFS) and long overall survival (OS) was comprised of in the cluster characterized by low levels of CCL-2, IL-6, IL-8, IL-10, and IL-12 at T0. Our data support the prognostic significance of longitudinal serum cytokine analysis. This approach may help identify patients for whom early treatment stop avoids needless toxicity or might justify treatment beyond early progression. Further investigations are required to validate this hypothesis.

Serum immuno-oncology markers carry independent prognostic information in patients with newly diagnosed metastatic breast cancer, from a prospective observational study

“…Elevated serum levels of IL-10 have been found in breast cancer patients compared to healthy controls, and IL-10 serum levels correlated with cancer stage [ 30 , 31 ]. To our knowledge, serum IL-10 has not previously been shown to be an independent prognostic marker for survival in MBC, only in combination with other serum cytokines [ 31 , 32 ]. In our study, elevated serum levels of IL-10 were shown to be an independent prognostic factor for both worse OS and PFS in multivariable analysis.…”

Baseline Cytokine Profile Identifies a Favorable Outcome in a Subgroup of Colorectal Cancer Patients Treated with Regorafenib

“…Our group has used PCA to identify a cytokinome signature able to discriminate different prognostic groups among end-stage patients affected by different solid tumors [ 44 ] and in breast cancer patients to identify a signature potentially able to select patients for treatment beyond progression [ 45 ]. However, to the best of our knowledge, this is the first study on colorectal cancer using PCA to evaluate a cytokine profile in patients with metastatic disease treated with standard therapy.…”

Excess body weight significantly affects systemic and tumor inflammatory status and correlates to poor prognosis parameters in patients with breast cancer

“…In BC, the Th2 pattern is associated with developing tumors with worse prognosis and survival. ( Paccagnella et al., 2022 ; Abeen, et al, 2018 ). Even though reduced IL-12 has been reported in BC patients ( Tzang et al., 2020 ), we did not observe this change when considering the BMI categorization.…”