Detection of Circulating Tumor Cells in the Prognostic Significance of Patients With Breast Cancer: A Retrospective Study

Overview

Journal J Clin Lab Anal

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
Pathology

Date 2024 Dec 18

PMID 39692703

Authors

Wanwen Xu

Feng Yuan

Affiliations

Soon will be listed here.

Abstract

Background: Breast cancer (BC) is an aggressive tumor. Circulating tumor cells (CTCs) are a potential biomarker for the prognosis of cancer patients. This study aimed to explore the prognostic significance of CTCs in patients with BC.

Methods: Retrospectively, 108 BC patients were collected between January 2011 and December 2019, while 10 patients with benign nodules were included as controls. CTCs with different phenotypes of patients were isolated using CanPatrol and tricolor RNA in situ hybridization (RNA-ISH) methods. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2) levels were measured by immunohistochemistry (IHC). The progression-free survival (PFS) was calculated using the Kaplan-Meier method. Independent risk factors for BC recurrence were determined by Cox proportional risk regression analysis.

Results: The higher the cancer stage (p = 0.00), the higher the ki-67 expression level (p < 0.01), and the lower the histologic grade (p < 0.01), the higher the number of CTCs. The PFS of patients with high CTCs was shorter than that of patients with low CTCs (p < 0.05). Total CTCs (≥ 6) and positive mesenchymal CTCs (MCTCs) were also associated with recurrence and metastasis.

Conclusions: Total CTCs in BC patients have an independent influence on PFS reduction. Higher total CTCs and MCTCs in peripheral blood are biomarkers for predicting the prognosis of BC patients. HER-2 high expression is also associated with the prognosis of the disease.

References

Ujiie D, Matsumoto T, Endo E, Okayama H, Fujita S, Kanke Y . Circulating tumor cells after neoadjuvant chemotherapy are related with recurrence in esophageal squamous cell carcinoma. Esophagus. 2021; 18(3):566-573. DOI: 10.1007/s10388-021-00829-x. View

Burstein H, Temin S, Anderson H, Buchholz T, Davidson N, Gelmon K . Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: american society of clinical oncology clinical practice guideline focused update. J Clin Oncol. 2014; 32(21):2255-69. PMC: 4876310. DOI: 10.1200/JCO.2013.54.2258. View

Bray F, Laversanne M, Sung H, Ferlay J, Siegel R, Soerjomataram I . Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024; 74(3):229-263. DOI: 10.3322/caac.21834. View

Wang Y, Liu Y, Zhang L, Tong L, Gao Y, Hu F . Vimentin expression in circulating tumor cells (CTCs) associated with liver metastases predicts poor progression-free survival in patients with advanced lung cancer. J Cancer Res Clin Oncol. 2019; 145(12):2911-2920. PMC: 6861204. DOI: 10.1007/s00432-019-03040-9. View

Xiao J, Pohlmann P, Isaacs C, Weinberg B, He A, Schlegel R . Circulating Tumor Cells: Technologies and Their Clinical Potential in Cancer Metastasis. Biomedicines. 2021; 9(9). PMC: 8467892. DOI: 10.3390/biomedicines9091111. View

Masuda T, Hayashi N, Iguchi T, Ito S, Eguchi H, Mimori K . Clinical and biological significance of circulating tumor cells in cancer. Mol Oncol. 2016; 10(3):408-17. PMC: 5528976. DOI: 10.1016/j.molonc.2016.01.010. View

Werner S, Heidrich I, Pantel K . Clinical management and biology of tumor dormancy in breast cancer. Semin Cancer Biol. 2021; 78:49-62. DOI: 10.1016/j.semcancer.2021.02.001. View

Hyun K, Koo G, Han H, Sohn J, Choi W, Kim S . Epithelial-to-mesenchymal transition leads to loss of EpCAM and different physical properties in circulating tumor cells from metastatic breast cancer. Oncotarget. 2016; 7(17):24677-87. PMC: 5029733. DOI: 10.18632/oncotarget.8250. View

Jahanzeb M . Adjuvant trastuzumab therapy for HER2-positive breast cancer. Clin Breast Cancer. 2008; 8(4):324-33. DOI: 10.3816/CBC.2008.n.037. View

10.

Wei T, Zhang X, Zhang Q, Yang J, Chen Q, Wang J . Vimentin-positive circulating tumor cells as a biomarker for diagnosis and treatment monitoring in patients with pancreatic cancer. Cancer Lett. 2019; 452:237-243. DOI: 10.1016/j.canlet.2019.03.009. View

11.

Ramos-Medina R, Lopez-Tarruella S, Del Monte-Millan M, Massarrah T, Martin M . Technical Challenges for CTC Implementation in Breast Cancer. Cancers (Basel). 2021; 13(18). PMC: 8466817. DOI: 10.3390/cancers13184619. View

12.

Sotiriou C, Pusztai L . Gene-expression signatures in breast cancer. N Engl J Med. 2009; 360(8):790-800. DOI: 10.1056/NEJMra0801289. View

13.

Truin W, Voogd A, Vreugdenhil G, van der Heiden-van der Loo M, Siesling S, Roumen R . Effect of adjuvant chemotherapy in postmenopausal patients with invasive ductal versus lobular breast cancer. Ann Oncol. 2012; 23(11):2859-2865. DOI: 10.1093/annonc/mds180. View

14.

Romond E, Perez E, Bryant J, Suman V, Geyer Jr C, Davidson N . Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005; 353(16):1673-84. DOI: 10.1056/NEJMoa052122. View

15.

Moon D, Lindsay D, Hong S, Wang A . Clinical indications for, and the future of, circulating tumor cells. Adv Drug Deliv Rev. 2018; 125:143-150. DOI: 10.1016/j.addr.2018.04.002. View

16.

Di Agostino S, Vahabi M, Turco C, Fontemaggi G . Secreted Non-Coding RNAs: Functional Impact on the Tumor Microenvironment and Clinical Relevance in Triple-Negative Breast Cancer. Noncoding RNA. 2022; 8(1). PMC: 8788502. DOI: 10.3390/ncrna8010005. View

17.

Ning N, Zhan T, Zhang Y, Chen Q, Feng F, Yang Z . Improvement of specific detection of circulating tumor cells using combined CD45 staining and fluorescence in situ hybridization. Clin Chim Acta. 2014; 433:69-75. DOI: 10.1016/j.cca.2014.02.019. View

18.

Arnedos M, Bihan C, Delaloge S, Andre F . Triple-negative breast cancer: are we making headway at least?. Ther Adv Med Oncol. 2012; 4(4):195-210. PMC: 3384094. DOI: 10.1177/1758834012444711. View

19.

Holmes M, Chen W, Li L, Hertzmark E, Spiegelman D, Hankinson S . Aspirin intake and survival after breast cancer. J Clin Oncol. 2010; 28(9):1467-72. PMC: 2849768. DOI: 10.1200/JCO.2009.22.7918. View

20.

Hall C, Karhade M, Bowman Bauldry J, Valad L, Kuerer H, DeSnyder S . Prognostic Value of Circulating Tumor Cells Identified Before Surgical Resection in Nonmetastatic Breast Cancer Patients. J Am Coll Surg. 2016; 223(1):20-9. PMC: 5868486. DOI: 10.1016/j.jamcollsurg.2016.02.021. View