Association of Alkaline Phosphatase, Lactate Dehydrogenase, and IL-1β Expression with Metastatic Bone Disease in Breast Cancer Patients: A Case-Control Study

Abstract

Background: Breast cancer is the most commonly diagnosed malignancy worldwide and frequently metastasises to bone, leading to significant morbidity and reduced survival among affected patients. Early identification of reliable biomarkers for metastatic bone disease remains critical for improving prognosis, guiding therapeutic decisions, and minimising skeletal-related complications. Aims: This study aimed to evaluate the associations of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and interleukin-1β (IL-1β) expression with metastatic bone disease (MBD) in breast cancer patients, and to determine their predictive value as risk markers. Study Design: Case-control study. Place and Duration of Study: The study was conducted at the Department of Orthopaedics and Oncology Outpatient Clinic, Prof. Dr. I.G.N.G Ngoerah General Hospital, Denpasar, Bali, Indonesia, between July and December 2024. Methodology: Forty-six female breast cancer patients aged 40–65 years were enrolled, including 26 patients with MBD (case group) and 20 without MBD (control group). Serum ALP and LDH levels were measured, and IL-1β expression was assessed via immunohistochemistry on primary tumor biopsy specimens. Bivariate analysis was performed using the Chi-square test, and multivariate logistic regression was used to identify independent predictors. The IL-1β cut-off value was determined by ROC curve analysis. Results: Elevated ALP was significantly associated with MBD (OR = 10.50; 95% CI: 2.01–54.77; P = .002). High LDH levels also showed significant association (OR = 7.60; 95% CI: 1.70–33.90; P = .004), as did elevated IL-1β expression (OR = 7.72; 95% CI: 1.80–33.04; P = .003). Multivariate analysis identified ALP (AOR = 11.84; 95% CI: 2.01–69.86; P = .006) and IL-1β expression (AOR = 7.49; 95% CI: 1.49–37.71; P = .015) as independent predictors of MBD. The combined predictive model demonstrated strong diagnostic accuracy (AUC = 0.821; 95% CI: 0.698–0.944), with 80% sensitivity and 75% specificity. Conclusion: Elevated ALP levels and high IL-1β expression are significantly associated with MBD in breast cancer patients and may serve as accessible predictive biomarkers for early identification of high-risk patients. The combination of ALP and IL-1β may support a cost-effective multimarker screening approach to enable timely clinical intervention and potentially reduce skeletal-related events. These associations, observed in a case-control design, do not establish causality, and prospective longitudinal studies are needed to determine whether biomarker elevations precede or result from bone metastasis. These findings should be validated in larger, multicenter cohorts.