Pre-Operative Combination of Normal BMI with Elevated YKL-40 and Leptin but Lower Adiponectin Level Is Linked to a Higher Risk of Breast Cancer Relapse: A Report of Four-Year Follow-Up Study

Abstract

Adipokines are powerful agents involved in the development of obesity-dependent cancers. This prospective study aimed to investigate the association between pre-treatment body mass index (BMI) and serum YKL-40, leptin, and adiponectin concentrations as well as the plasma activity of tissue factor (TF) and the future prognosis of early, non-metastatic breast cancer (BrC) subjects. The serum levels of YKL-40, leptin, and adiponectin as well as plasma TF activity, anthropometric parameters, and clinicopathological parameters were analysed in 81 treatment-naïve females with invasive BrC. The predictive value of YKL-40, BMI, leptin, adiponectin, and TF was determined with a 95% confidence interval (CI). Kaplan–Meier plots and log-rank and F Cox tests were used to determine the clinical outcomes of progression-free survival (PFS). The median follow-up duration was 44 months with complete follow-up for the first event. Follow-up revealed a significantly higher incidence of disease relapse in BrC patients with a high baseline concentration of YKL-40 (22.22%) and TF activity (21.43%). Body mass index was an independent predictor of survival, with women who were overweight/obese being less prone to relapse (hazard ratio (HR): 0.75; 95% CI: 0.59 to 0.95). The recurrence rates for normal-weight BrC cases was 21.05% versus 7.14% for their overweight counterparts. The receiver operating characteristic analysis showed the strong ability of the analysed biomarkers to predict disease progression, with an area under the receiver operating characteristics (ROC) curve of 0.84 (95% CI, 0.823 to 0.931). In a prospective cohort of invasive BrC patients, overweight/obesity was associated with improved future outcomes. The combination of a normal BMI with high leptin and low adiponectin levels and high TF activity was associated with an increased risk of recurrence and decreased survival.

The Complex Biology of the Obesity-Induced, Metastasis-Promoting Tumor Microenvironment in Breast Cancer

“…Undoubtedly, adiposity in obesity is the key influencer associated with the adverse progression of breast cancer. However, one clinical report showed increased numbers of cases of breast cancer recurrence concurrent with decreased survival in normal BMI breast cancer patients (BMI < 25 kg/m 2 ) with stage I and II disease, in comparison to obese or overweight BMI (BMI > 25 kg/m 2 ) patients [ 135 ]. Furthermore, another clinical report highlighted all the research studies demonstrating high BMI subjects with markedly improved immune-efficacy responses, following immune checkpoint blockade treatment in comparison to normal BMI subjects, despite the contradictory role of obesity in immunosuppression [ 136 ].…”

“…There is still no standardized alternative measure of body composition that considers age, sex, and the existence of varying ethnicities [ 137 ]. Hence, a well-planned clinical research study design with the proper timing of BMI determination (pre, peri, and post diagnosis as well as treatment), accounting for all the relevant covariables mentioned above, needs to be considered to find the answers for the relationship of obesity in carcinogenesis and cancer progression [ 135 , 137 ].…”

Evaluation of the body mass index in breast cancer prognosis in a cohort of small-stature overweight patients: multi-center study in China

“…Obesity may exacerbate estrogen production, lead to chronic subclinical inflammation, and increase circulating levels of proinflammatory proteins favoring cancer development (36). Bielawski's research showed that BMI is an independent predictor of survival, with overweight/ obese women being less prone to relapse (37). When we analyzed the BMI of patients belonging to different clinicopathological categories, we found a strong correlation between BMI and age.…”

The impact of obesity and adipokines on breast and gynecologic malignancies

“…This may reflect the upregulation of compensatory mechanisms in the setting of decreased adiponectin expression 74 . Increased adiponectin levels may be indicative of improved overall survival and disease‐free survival in breast cancer 73,76 . However, Obi et al.…”