The tetrad BMI, leptin, leptin/adiponectin (L/A) ratio and CA 15-3 are reliable biomarkers of breast cancer

Abstract

Background: Several studies have reported that leptin levels, the leptin/adiponectin (L/A) ratio and carbohydrate antigen (CA) 15-3 are especially elevated in breast cancer patients with high body mass index (BMI). The purpose of this study was to evaluate BMI, leptin, L/A ratio and CA 15-3 all together as reliable biomarkers for breast cancer.

Methods: Serum levels of leptin, adiponectin and CA 15-3, as well as anthropometric and biochemical parameters were analysed in 88 female patients who participated in a mammography study. Predictive values of BMI, leptin, L/A ratio and CA 15-3 were determined with a 95% confidence interval.

Results: Women were diagnosed with either breast cancer (n = 40) or benign breast lesions (n = 48). Among anthropometric parameters, age (P ≤ 0.001), weight (P ≤ 0.05) and waist circumference (P ≤ 0.02) were higher in patients with breast cancer than in patients without this pathology. The 75th percentile values for BMI, leptin, L/A ratio and CA 15-3 were 29.24 kg/m(2), 26.65 ng/ml, 2.37 and 18.45 IU, respectively. The suggested odds ratio for breast cancer patients with the values that were above the 75th percentile of the tetrad was 6.7 (0.7505-60.0665 confidence interval).

Conclusion: When the four variables were analysed together, a sensitivity of 83.3%, specificity of 80%, positive predictive value of 83.3% and negative predictive value of 80% were obtained. Results indicate that using the 75th percentile set points for BMI, leptin, L/A ratio and CA 15-3 together could offer a reliable approach to determine which women are at high risk for developing breast cancer.

Trial registration: ClinicalTrials.gov NCT01643148.

© 2012 Wiley Periodicals, Inc.

Figures

Figure 1

Relationship between sensitivity and specificity and the predictive power of biomarkers in breast cancer. (A) BMI > 29.24 kg/m2, (B) leptin > 26.65 ng/ml, (C) L/A ratio > 2.37, (D) CA 15‐3 > 18.45 IU, (E) BMI > 29.24 kg/m2 and leptin > 26.65 ng/ml, (F) BMI > 29.24 kg/m2 and CA 15‐3 > 18.45 IU, (G) BMI > 29.24 kg/m2, leptin > 26.65 ng/ml, L/A ratio > 2.37 and CA 15‐3 > 18.45 IU. BMI, body mass index; CA 15‐3, carbohydrate antigen 15‐3; L/A, leptin/adiponectin ratio.

Figure 2

Differences in tetrad biomarkers between breast cancer patients (cases; n = 40) and patients with benign breast disease (controls; n = 48). (A) BMI, (B) leptin, (C) L/A ratio and (D) CA 15‐3. BMI, body mass index; CA 15‐3, carbohydrate antigen 15‐3; L/A, leptin/adiponectin ratio.

Figure 3

ROC analysis in cases and controls of (A) leptin (AUC, 0.57 (95% CI, 0.64–0.71)) and waist circumference (AUC, 0.67 (95% CI, 0.6–0.82)); (B) BMI (AUC, 0.68 (95% CI, 0.56–0.79)), leptin (AUC, 0.59 (95% CI, 0.46–0.71)), L/A ratio (AUC, 0.53 (95% CI, 0.41–0.65)) and CA 15‐3 (AUC, 0.71 (95% CI, 0.6–0.82)); (C) BMI (AUC, 0.67 (0.55–0.78)), leptin (AUC, 0.57 (95% CI, 0.45–0.7)), L/A ratio (AUC, 0.52 (95% CI, 0.4–0.65)), CA 15‐3 (AUC, 0.69 (95% CI, 0.58–0.81)), waist circumference (AUC, 0.67 (95% CI, 0.56–0.79)), age (AUC, 0.74 (95% CI (0.64–0.85)) and weight (AUC, 0.62 (95% CI (0.5–0.74)). AUC, area under the curve; BMI, body mass index; CA 15‐3, carbohydrate antigen 15‐3; L/A, leptin/adiponectin ratio; ROC, receiver operator characteristic.