FGF-BASIC, PDGF-BB, and IL-12 P40 plasma levels predict breast cancer treatment response in Peruvian women
Background
Breast cancer (BC) is the most common malignancy in women globally, with significant mortality despite therapeutic advances. Beyond established hormonal and genetic factors, cytokines are increasingly recognized for their critical roles in driving tumor aggressiveness and fostering therapeutic resistance. However, comprehensive data on circulating cytokine profiles and their prognostic value in diverse populations, particularly in Latin American populations like Peru, remains limited. This gap hinders the development of population-specific biomarkers and personalized treatment strategies for breast cancer.
Study Design
This prospective cohort study enrolled 88 breast cancer patients with clinical stage II-III from three major cancer centers in Peru. Plasma samples were meticulously collected from all participants prior to the initiation of any treatment. These samples were then analyzed using the Bio-Plex Pro™ Human Cytokine 48-Plex Screening Panel kit to characterize a broad spectrum of circulating cytokine profiles. The primary objective was to evaluate the association between these cytokine levels and both complete pathological response (pCR) and overall clinical response to subsequent treatments, utilizing Poisson regression models for statistical analysis.
Results
Significant differences in plasma concentrations of MIP-1β, IL-9, GRO-α, and TNF-β were observed across various breast cancer molecular subtypes. Crucially, the study identified several cytokines associated with treatment response. Lower circulating levels of FGF BASIC were found to be necessary to increase the relative risk of achieving a complete pathological response (pCR), with a relative risk of 0.9779 (95% CI 0.9573-0.9989; p=0.0392). This suggests a potential inverse relationship between FGF BASIC and treatment efficacy. Furthermore, decreased levels of FGF BASIC, PDGF BB, SDF-1, IL-12 P40, and IL-8 were all associated with an increased likelihood of favorable clinical responses to treatment. Multivariable analyses, designed to account for confounding factors, confirmed that only FGF-BASIC, PDGF-BB, and IL-12 P40 remained independently and significantly associated with improved clinical response.
Lower circulating FGF BASIC increased the relative risk of achieving pCR (RR = 0.9779; 95% CI 0.9573-0.9989; p=0.0392).
Key Findings
- Differences in
MIP-1β,IL-9,GRO-α, andTNF-βconcentrations were observed between breast cancer molecular subtypes. - Lower circulating
FGF BASIClevels increased the relative risk of achieving pCR (RR = 0.9779; p=0.0392). - Decreased
FGF BASIC,PDGF BB,SDF-1,IL-12 P40, andIL-8levels were associated with increased clinical responses. - Multivariable analysis confirmed
FGF-BASIC,PDGF-BB, andIL-12 P40as independently associated with clinical response.
Why It Matters
This research provides critical insights into the tumor microenvironment and systemic immune responses in breast cancer patients, specifically within a Peruvian cohort. Identifying plasma cytokine profiles linked to treatment response, particularly FGF-BASIC, PDGF-BB, and IL-12 P40, opens new avenues for prognostic biomarker development. Clinicians could potentially use these cytokine profiles to stratify patients before treatment, guiding personalized therapeutic decisions and optimizing treatment selection. While this is an observational study, these findings lay the groundwork for future interventional studies exploring whether modulating these cytokine pathways could enhance treatment efficacy. This moves us closer to understanding how systemic inflammation impacts cancer outcomes and how to leverage this knowledge for better patient care.
breast-cancer
cytokines
biomarkers
prognosis
treatment-response
inflammation