Correlation analysis of HIF-1α and Ca15-3 in response to neoadjuvant chemotherapy in locally advanced breast cancer: A cohort study in Indonesia

Article type: Research Article

Authors: Manginstar, Christian^{a; b} | Oley, Mendy Hatibie^{c; d;} | Oley, Maximillian Christian^{e; f} | Merung, Marselus^{a; b} | Langi, Fima Lanra Fredrik G.^g | Kepel, Billy Johnson^h | Rusli, Lie Vennyⁱ | Islam, Andi Asadul^j | Faruk, Muhammad^k

Affiliations: [a] Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Sam Ratulangi University, Manado, North Sulawesi, Indonesia | [b] Division of Surgical Oncology, Department of Surgery, R. D. Kandou Hospital, Manado, North Sulawesi, Indonesia | [c] Division of Plastic Reconstructive & Aesthetic Surgery, Department of Surgery, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia | [d] Division of Plastic Reconstructive & Aesthetic Surgery, Department of Surgery, R. D. Kandou Hospital, Manado, North Sulawesi, Indonesia | [e] Division of Neurosurgery, Department of Surgery, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia | [f] Division of Neurosurgery, Department of Surgery, R. D. Kandou Hospital, Manado, North Sulawesi, Indonesia | [g] Department Epidemiology and Biostatistics, Public Health Faculty, Sam Ratulangi University, Manado, Indonesia | [h] Department of Chemistry, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia | [i] Department of Surgery, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia | [j] Department of Neurosurgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia | [k] Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

Correspondence: [*] Corresponding author: Mendy Hatibie Oley, Division of Plastic Reconstructive & Aesthetic Surgery, Department of Surgery, Faculty of Medicine, Sam Ratulangi University, Jalan Raya Tanawangko No.56, Malalayang Satu Barat, Malalayang, Manado, North Sulawesi, 95162, Indonesia. Fax: +62 431 863786; E-mail: [email protected]. ORCIDs: https://orcid.org/0000-0003-2750-5917 (M.H. Oley); https://orcid.org/0000-0001-8317-0790 (M.C. Oley); https://orcid.org/0000-0002-2730-8836 (F.L.F.G. Langi); https://orcid.org/0000-0002-7079-4585 (M. Faruk)

Abstract: BACKGROUND:Breast cancer (BC) is the most common cancer among women worldwide and a leading cause of death in Indonesia. The primary treatment of locally advanced BC is neoadjuvant chemotherapy (NAC). The rapid proliferation of tumor cells in a neoplastic microenvironment is largely due to hypoxia, which also encourages the development of chemoresistant BC. The master regulator of the hypoxia response is hypoxia-inducible factor-1α (HIF-1α). The response evaluation criteria in solid tumors (RECIST) is an objective response metric that demonstrates the efficacy of a NAC based mostly on the size of the tumor. Ca15-3 is the protein product of the MUC1 gene and is the most widely used serum marker in BC. The purpose of this study is to investigate the relationship between HIF-1α and RECIST and between Ca15-3 and RECIST and to assess the relationship among all of them in BC. METHODS:This observational study used the prospective cohort method included 11 patients with histopathologically confirmed BC, specifically invasive ductal carcinoma. We evaluated the changes in HIF-1α and Ca15-3 serum levels using ELISA and measured tumor lesions with RECIST. The procedure was carried out twice. Serum levels were measured at baseline, and after receiving two cycles of NAC (5 weeks). RESULTS:Among the 11 patients included in this study, HIF-1α, Ca15-3, and RECIST decreased significantly after NAC. The changes in RECIST correlated with Ca15-3: each unit decrease in RECIST score was associated with a 0.3-unit decrease in Ca15-3 levels (p = 0.019). CONCLUSIONS:There was a decrease in HIF-1α, followed by a decrease in Ca15-3 and RECIST in response to chemotherapy. There was a statistically significant correlation between Ca15-3 and response to chemotherapy. This study evidences the relationship between factors that shape the local tumor microenvironment.

Keywords: Breast cancer, neoadjuvant chemotherapy, ductal carcinoma, Ca15-3, RECIST, HIF1α

DOI: 10.3233/BD-229004

Journal: Breast Disease, vol. 41, no. 1, pp. 481-487, 2022