Correlation between carcinoembryonic antigen, cancer antigen 15-3, and neutrophil–lymphocyte ratio on metastasis and progression-free survival of breast cancer

Muhammad Alim Al Fath  Rianse; Salman Ardi Syamsu; John Pieter Jr; Prihantono  Prihantono; Firdaus	 Hamid; Rina  Masadah; Muhammad  Faruk

doi:10.23750/abm.v95i4.15720

Correlation between carcinoembryonic antigen, cancer antigen 15-3, and neutrophil–lymphocyte ratio on metastasis and progression-free survival of breast cancer

Authors

Muhammad Alim Al Fath Rianse Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
Salman Ardi Syamsu Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
John Pieter Jr Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
Prihantono Prihantono Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia https://orcid.org/0000-0002-8247-0457
Firdaus Hamid Department of Microbiology Clinic, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia https://orcid.org/0000-0003-1788-0836
Rina Masadah Department of Pathology Anatomy, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia https://orcid.org/0000-0002-1380-4759
Muhammad Faruk Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia https://orcid.org/0000-0002-7079-4585

DOI: https://doi.org/10.23750/abm.v95i4.15720

Keywords:

breast cancer, progression-free survival, cancer antigen 15-3, neutrophil–lymphocyte ratio, carcinoembryonic antigen

Abstract

Background and aim: Blood and tumor markers have been studied as predictive and prognostic factors in breast cancer (BC). To assess the relationships of the tumor markers cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) and the neutrophil–lymphocyte ratio (NLR) with the incidence of metastasis and progression-free survival (PFS) in BC. Methods: This observational analytical study used a cohort design. The population was BC patients who had undergone mastectomy or breast-conserving treatment. Patients received CEA and CA 15-3 examinations and were assessed radiologically for metastases, with follow-up of up to 24 months. Differences in patient PFS levels depending on NLR, CEA, and CA 15-3 were assessed using Kaplan–Meier analysis. Results: One male and 159 female patients were included, with a mean age of 48.3 ± 9.18 years. The mean NLR, CEA, and CA 15-3 were 22.51 ± 94.1, 73.05 ± 212.99, and 2.56 ± 3.48, respectively. Based on a mean PFS of 12.16 ± 0.45, 38.4% of patients experienced metastases. A significant relationship with the incidence of metastasis existed for CA 15-3 and CEA levels but not NLR. Likewise, PFS did not show a significant relationship with NLR, CA 15-3, or CEA. Survival analysis showed no significant relationship. Conclusions: CEA and CA 15-3 can be negative prognostic factors for BC metastasis. These results can be compared with other studies, specifically answering the role of predictive and prognostic factors of NLR, CEA, and CA 15-3 in BC patients.

References

Prihantono P, Rusli R, Christeven R, Faruk M. Cancer Incidence and Mortality in a Tertiary Hospital in Indonesia: An 18-Year Data Review. Ethiop J Health Sci. 2023;33(3):515-522. doi:10.4314/ejhs.v33i3.15

Lei S, Zheng R, Zhang S, et al. Global patterns of breast cancer incidence and mortality: A population‐based cancer registry data analysis from 2000 to 2020. Cancer Commun. 2021;41(11):1183-1194. doi:10.1002/cac2.12207

Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660

Prihantono P, Faruk M. Neoadjuvant chemotherapy response, disease-free survival, and overall survival of breast cancer in a single institution. Surg open Sci. 2023;15:19-25. doi:10.1016/j.sopen.2023.07.016

Corbeau I, Jacot W, Guiu S. Neutrophil to Lymphocyte Ratio as Prognostic and Predictive Factor in Breast Cancer Patients: A Systematic Review. Cancers (Basel). 2020;12(4). doi:10.3390/cancers12040958.

Atalay C. Are CA 15-3, CEA and CA 125 Predictors for Lymphatic and Vascular Spread In Breast Cancer? Erciyes Med J. 2008;30(4):218-224.

Co M, Man V, Kwong A. Serum tumor markers and positron emission tomography-computed tomography scan as post-breast cancer treatment surveillance. Ann Breast Surg. 2019;3:1-6. doi:10.21037/abs.2019.10.01.

Shao Y, Sun X, He Y, Liu C, Liu H. Elevated Levels of Serum Tumor Markers CEA and CA15-3 Are Prognostic Parameters for Different Molecular Subtypes of Breast Cancer. PLoS One. 2015;10(7):e0133830. doi:10.1371/journal.pone.0133830.

Handy B. The Clinical Utility of Tumor Markers. Lab Med. 2009;40(2):99-103. doi:10.1309/LMTRKSKYW4GI6SBJ.

Fakhari A, Gharepapagh E, Dabiri S, Gilani N. Correlation of cancer antigen 15-3 (CA15-3) serum level and bony metastases in breast cancer patients. Med J Islam Repub Iran. 2019;33:142. doi:10.34171/mjiri.33.142.

Kumar A, Das SK, Emdad L, Fisher PB. Applications of tissue-specific and cancer-selective gene promoters for cancer diagnosis and therapy. In: Tew KD, Fisher PB, editors. Advances in Cancer Research. London: Academic Press; 2023. pp. 253-315. doi:10.1016/bs.acr.2023.03.005.

Gago-Dominguez M, Matabuena M, Redondo CM, et al. Neutrophil to lymphocyte ratio and breast cancer risk: analysis by subtype and potential interactions. Sci Rep. 2020;10(1):13203. doi:10.1038/s41598-020-70077-z.

Woodford RG, Zhou DD ‐X, Kok PS, et al. The validity of progression‐free survival 2 as a surrogate trial end point for overall survival. Cancer. 2022;128(7):1449-1457. doi:10.1002/cncr.34085.

Beauchemin C, Cooper D, Yelle L, Lachaine J, Lapierre M-E. Progression-free survival as a potential surrogate for overall survival in metastatic breast cancer. Onco Targets Ther. Published online June 2014:1101. doi:10.2147/OTT.S63302.

Orditura M, Galizia G, Diana A, et al. Neutrophil to lymphocyte ratio (NLR) for prediction of distant metastasis-free survival (DMFS) in early breast cancer: a propensity score-matched analysis. ESMO open. 2016;1(2):e000038. doi:10.1136/esmoopen-2016-000038.

Inoue Y, Fujishima M, Ono M, et al. Clinical significance of the neutrophil-to-lymphocyte ratio in oligometastatic breast cancer. Breast Cancer Res Treat. 2022;196(2):341-348. doi:10.1007/s10549-022-06726-w.

Ivars Rubio A, Yufera JC, de la Morena P, et al. Neutrophil-lymphocyte ratio in metastatic breast cancer is not an independent predictor of survival, but depends on other variables. Sci Rep. 2019;9(1):16979. doi:10.1038/s41598-019-53606-3.

Lou C, Jin F, Zhao Q, Qi H. Correlation of serum NLR, PLR and HALP with efficacy of neoadjuvant chemotherapy and prognosis of triple-negative breast cancer. Am J Transl Res. 2022;14(5):3240-3246. PMID: 35702128.

Khushk M, Khan A, Rehman A, et al. The Role of Tumor Markers: Carcinoembryonic Antigen and Cancer Antigen 15-3 in Patients With Breast Cancer. Cureus. 2021;13(7):e16298. doi:10.7759/cureus.16298.

Kabel AM. Tumor markers of breast cancer: New prospectives. J Oncol Sci. 2017;3(1):5-11. doi:10.1016/j.jons.2017.01.001.

He Z-Y, Li X, Chen Q-S, et al. Elevated serum carcinoembryonic antigen and CA15-3 levels and the risk of site-specific metastases in metastatic breast cancer. Transl Cancer Res. 2016;5(5):529-537. doi:10.21037/tcr.2016.08.39.

Laessig D, Nagel D, Heinemann V, et al. Importance of CEA and CA 15-3 during disease progression in metastatic breast cancer patients. Anticancer Res. 2007;27(4A):1963-1968. PMID: 17649806.

Jiang N, Tian T, Chen X, et al. A Diagnostic Analysis Workflow to Optimal Multiple Tumor Markers to Predict the Nonmetastatic Breast Cancer from Breast Lumps. Zhao D, ed. J Oncol. 2021;2021:1-10. doi:10.1155/2021/5579373.

Geng B, Liang M-M, Ye X-B, Zhao W-Y. Association of CA 15-3 and CEA with clinicopathological parameters in patients with metastatic breast cancer. Mol Clin Oncol. 2015;3(1):232-236. doi:10.3892/mco.2014.419.

Yang Y, Zhang H, Zhang M, Meng Q, Cai L, Zhang Q. Elevation of serum CEA and CA15-3 levels during antitumor therapy predicts poor therapeutic response in advanced breast cancer patients. Oncol Lett. 2017;14(6):7549-7556. doi:10.3892/ol.2017.7164.

Nam SE, Lim W, Jeong J, et al. The prognostic significance of preoperative tumor marker (CEA, CA15-3) elevation in breast cancer patients: data from the Korean Breast Cancer Society Registry. Breast Cancer Res Treat. 2019;177(3):669-678. doi:10.1007/s10549-019-05357-y.

M FR, Rikarni R, Harminarti N. Hubungan Kadar Cancer Antigen 15-3 Serum dengan Metastasis Kanker Payudara. J Ilmu Kesehat Indones. 2021;1(3):371-378. doi:10.25077/jikesi.v1i3.110.

Hasan D. Diagnostic impact of CEA and CA 15-3 on chemotherapy monitoring of breast cancer patients. J Circ biomarkers. 2022;11:57-63. doi:10.33393/jcb.2022.2446.

Wang W, Xu X, Tian B, et al. The diagnostic value of serum tumor markers CEA, CA19-9, CA125, CA15-3, and TPS in metastatic breast cancer. Clin Chim Acta. 2017;470:51-55. doi: 10.1016/j.cca.2017.04.023.

Uehara M, Kinoshita T, Hojo T, Akashi-Tanaka S, Iwamoto E, Fukutomi T. Long-term prognostic study of carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA 15-3) in breast cancer. Int J Clin Oncol. 2008;13(5):447. doi:10.1007/s10147-008-0773-3.

Lee JS, Park S, Park JM, Cho JH, Kim S Il, Park B-W. Elevated levels of serum tumor markers CA 15-3 and CEA are prognostic factors for diagnosis of metastatic breast cancers. Breast Cancer Res Treat. 2013;141(3):477-484. doi:10.1007/s10549-013-2695-7.