BACKGROUND: Carbohydrate antigens 15-3 (CA 15-3) is a conventional tumor marker in breast cancer, with low sensitivity and specificity. MicroRNA (miRNA)-21 showed its stability in circulation and could serve as powerful biomarker. The aim of this study was to evaluate miRNA-21 as breast cancer biomarker compared to CA 15-3 in Indonesian population.METHODS: Circulating plasma miRNA-21 expression was measured using qRT-PCR in 49 patients at various stages of breast cancer and 16 healthy controls. The relative expression value of miRNA-21 was calculated using 2-ΔΔCt. Meanwhile, CA 15-3 was quantified using electrochemiluminescence immunoassay (ECLIA) methods. The results of miRNA-21 and CA 15-3 plasma circulating expression were compared with controls at each stage and between stages of breast cancer.RESULTS: CA 15-3 median level in breast cancer group was 1.60 times higher compared to control group (p=0.019), 21.00 m/mL and 13.05 m/mL, respectively. Median miRNA-21 expression in breast cancer group was elevated 4.92 folds compared to control group (p=0.001), 4.43 and 0.90, respectively. There was no significant difference of CA 15-3 level between controls and all stages of breast cancer group. CA 15-3 cut-off value was 15.05 m/mL (p=0.016) with 59.2% sensitivity and 62.5% specificity. Meanwhile, there was a significant difference of miRNA-21 expression between controls and most stages of breast cancer group. Circulating miRNA-21 expression cut-off value was 2.07 (p=0.000) with 91.8% sensitivity and 87.5% specificity.CONCLUSION: Circulating miRNA-21 expression and CA 15-3 levels were significantly increased in breast cancer group compared to control group. The miRNA-21 expression increased consistently with breast cancer stage progression. miRNA-21 could serve as superior biomarker compared to CA 15-3.KEYWORDS: biomarker, breast cancer, circulating plasma, liquid biopsy, miRNA-21

Breast cancer is still global burden especially for woman with 2.3 million cases every year dan 15% mortality among cancer diseases. In developing countries, most of the cases are diagnosed at terminal stage when metastasis already found. Bone metastasis is the highest among other metastasis sites such as: lung, liver and brain. Bone metastasis will cause hypercalcemia and bone pain as complications.  Both will gradually decrease patient’s quality of life. Comprehensive and holistic management for these complications will reduce deterioration and hopefully increase patient’s quality of life even they were at terminal stage. We describe a 40-year-old woman who got hypercalcemia crisis. Hypercalcemia usually manifest as a consequence of other diseases. Epidemiologically, majority come from metastasis, but can be other diseases, such as multiple myeloma. Interestingly, during medical investigation through her medical history, and physical examination, and laboratory examinations, we conclude that her hypercalcemia crisis was caused by bone metastasis from breast cancer.

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