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.

Kornel Bielawski,Marek Bulsa,Barbara Ruszkowska-Ciastek,Piotr Rhone

doi:10.3390/jcm9061742

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.

Highlights

It is well-established that breast cancer (BrC) and obesity are the most widespread diseases in the female population, all over the world
The multivariate Cox hazards analysis, which takes into account the function of time, revealed that the activity of tissue factor (HR, 1.07; 95% confidence interval (CI), 1.01–1.14; p = 0.0240), leptin concentration (HR, 1.21; 95% CI, 1.02–1.44; p = 0.0327), body mass index (BMI) (HR, 0.75; 95% CI, 0.59–0.95; p = 0.0178), and adiponectin level (HR, 0.86; 95% CI, 0.76–0.97; p = 0.0135) were significant predictive factors for disease relapse in BrC subjects
According to the multivariate Cox proportional risk model and the excellent area under the receiver operating characteristics (ROC) curve for the tested model, we have demonstrated the usefulness of applying pre-treatment YKL-40, BMI, leptin, and adiponectin levels and tissue factor (TF) activity together as biomarkers for predicting disease relapse

Summary

Introduction

It is well-established that breast cancer (BrC) and obesity are the most widespread diseases in the female population, all over the world. There is no doubt that obesity is a well-identified risk factor for cervical, ovarian, endometrial, and breast cancer, and it is associated with 88% mortality rates in females [1,2]. One in two breast cancer women are overweight or obese [2]. Obesity leads to increased susceptibility for postmenopausal luminal breast cancers, but premenopausal obese women are more prone to developing a basal-like breast cancer (BLBC). Adiposity is associated with a more aggressive breast cancer phenotype, including larger tumours, more often with nodal metastases and worse prognosis [3,4,5,6]. Adiposity is linked with both cancer predisposition and cancer-dependent death [7]

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