Clinical, Histopathological, and Biomarker Predictors of Bone Scintigraphy Positivity in Breast Cancer: A Retrospective Study

Abstract

Breast cancer is the most commonly diagnosed malignancy in Indonesia, and bone is the most frequent site of distant metastasis, typically detected by bone scintigraphy. Limited access to nuclear medicine services in many regions may delay the detection of skeletal metastases. Identifying reliable clinical, histopathological, molecular, and serum biomarker predictors is therefore essential to prioritize high-risk patients for earlier imaging. This study evaluated clinical, histopathological, molecular, and serum biomarker predictors of bone scintigraphy positivity in breast cancer patients.

This retrospective study included 225 breast cancer patients who underwent bone scintigraphy at Dr. Hasan Sadikin General Hospital, Indonesia. Data on age, tumor laterality, CA15-3, histological subtype, histological grade, immunohistochemical markers, and molecular subtype were analyzed. Univariate analysis, receiver operating characteristic analysis, and multivariable binary logistic regression were performed.

Bone scintigraphy positivity was not significantly associated with age at scan, age at diagnosis, or tumor laterality. Higher CA15-3 levels were significantly associated with positive bone scan findings (p < 0.001), with moderate discriminatory performance (area under the curve = 0.690). The optimal CA15-3 cutoff was 19.75 U/mL, yielding 49.1% sensitivity and 86.0% specificity. Histological grade, molecular subtype, and Ki-67 were significantly associated with bone scan positivity in univariate analysis. In multivariable analysis, only log-transformed CA15-3 and Ki-67 >20% remained independently associated with positive bone scan findings. Log-transformed CA15-3 increased the odds of bone scan positivity by 4.289-fold (adjusted odds ratio [OR]: 4.289; 95% confidence interval [CI]: 1.836–10.022; p < 0.001), while Ki-67 >20% increased the odds by 5.520-fold (adjusted OR: 5.520; 95% CI: 1.210–25.184; p = 0.027).

CA15-3 level and Ki-67 >20% were independent predictors of bone scintigraphy positivity in breast cancer patients. These markers may help support risk stratification and prioritization for skeletal imaging, particularly in settings with limited nuclear medicine access.