1548 Bali Medical Journal 2022; 11(3): 1548-1552 | doi: 10.15562/bmj.v11i3.3611 ORIGINAL AERTICLE ABSTRACT Association between serum TNF-α level with the incidence of metastases in women with breast cancer in Dr. Soetomo General Hospital, Indonesia Rachman Efendi 1 , Husnul Ghaib 2 , Iskandar Ali 2* Background: Breast cancer is the most common cancer in women. The occurrence of metastasis in breast cancer should be detected early. Tumor necrosis factor-α (TNF-α) is involved in every step of the carcinogenesis process. A rise in TNF-α level is linked to the advancement of breast cancer. We aimed to determine the association between TNF-α levels and breast cancer metastases. Methods: An analytic cross-sectional study was conducted on women with breast cancer treated at the Oncology Surgery Center between November 2021 and April 2022. The patient’s data were collected from the medical record, including age, menopausal status, tumor size and lymph node involvement, and tumor subtype. The serum TNF-α level was measured using ELISA. The optimal cut-of value was determined using the receiver operating characteristics analysis. The association between serum TNF-α and the incidence of breast cancer metastases was analyzed using SPSS version 26 for Windows. Results: We analyzed a total of 50 patients. The mean age was 48.8 ± 8.3 years. The serum TNF-α level was divided into high- TNF-α and low-TNF-α using a cut-of value of 22.755 pg/mL. There were 27 patients (27/50; 54.0%) with high serum TNF-α levels and 23 patients (23/50; 46.0%) with low TNF-α levels. The sensitivity, specifcity, positive predictive value, negative predictive value, and accuracy were 73.9%, 63.0%, 63,0%, 73,9%, and 68%, respectively. There was a statistically signifcant association between serum TNF-α levels and metastatic breast cancer (p=0.009). Conclusion: There was a signifcant association between TNF-α levels and metastatic breast cancer. Serum TNF-α may be a potential biomarker to detect metastasis in breast cancer patients. Keywords: advanced-stage cancer, breast cancer, metastases, TNF-α. Cite This Article: Efendi, R., Ghaib, H., Ali, I. 2022. Association between serum TNF-α level with the incidence of metastases in women with breast cancer in Dr. Soetomo General Hospital, Indonesia. Bali Medical Journal 11(3): 1548-1552. DOI: 10.15562/ bmj.v11i3.3611 1 Department of Surgery, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Hospital, Surabaya, Indonesia; 2 Oncology Surgery Division, Department of Surgery, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Hospital, Surabaya, Indonesia; *Corresponding author: Iskandar Ali; Oncology Surgery Division, Department of Surgery, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Hospital, Surabaya, Indonesia; iskandarali1983@yahoo.com Received: 2022-08-02 Accepted: 2022-10-06 Published: 2022-11-13 1548 Bali Medical Journal (Bali MedJ) 2022, Volume 11, Number 3: 1548-1552 P-ISSN.2089-1180, E-ISSN: 2302-2914 Open access: www.balimedicaljournal.org INTRODUCTION Te most prevalent disease in women, breast cancer, is a prominent cause of death in both developed and developing nations. According to the International Agency for Research on Cancer (IARC), the number of new cases of breast cancer diagnosed worldwide in 2018 was roughly 2.1 million (11.6%). 1,2 Breast cancer afects 0.5 out of every 1000 women in Indonesia. 3 Approximately 70% of breast cancer patients at Dr. Soetomo General Hospital were in an advanced stage. 4,5 In 2002-2006, Cancer Research UK found that patients who present at an early stage have a 90% chance of survival, whereas those who present at an advanced stage have just a 15% survival rate. 6 Metastatic breast cancer is a primary cause of increased mortality and morbidity. Te most common metastases in breast cancer patients at Dr. Soetomo General Hospital were bone, lung, and liver. More than 30% of breast cancer patients die from metastatic breast cancer. Understanding the mechanism of tumor cell invasion and metastasis is one of the most challenging tasks in cancer research. 7 Te occurrence of metastases in breast cancer must be detected early for the patient to receive the best treatment to increase the survival rate and the quality of life. Chest X-rays, bone scans, ultrasonography (USG), Computed Tomography scans (CT scans), and magnetic resonance imaging (MRI) can all be used to detect metastases. However, most of these examination techniques are expensive, require special skills, and are only available at a limited number of healthcare facilities. 8 One of the cytokines released by active macrophages is Tumor Necrosis Factor- Alpha (TNF-α). TNF-α may promote proliferation, migration, and metastasis in cancer cells. 9 TNF-α is involved in various steps of the carcinogenesis process. TNF-α causes the initiation and promotion of tumors by activating NF-kB, PKCa and AP-1-dependent pathways. TNF-α also activates NF-kB and increases tumor cell proliferation to increase tumor cell survival. In addition, TNF-α promotes tumor angiogenesis by interacting with IL-8 and VEGF. Trough NF-kB, chemokine receptor (CXCR4), monocyte chemoattractant protein-1 (MCP-1), IL- 8, and intercellular adhesion molecule-1,