Monitoring Serum HER2 Levels in Breast Cancer Patients

Overview

Journal Springerplus

Date 2015 Jun 13

PMID 26069876

Citations 11

Authors

Julia Tchou

Lian Lam

Yun Rose Li

Claire Edwards

Bonnie Ky

Hongtao Zhang

Affiliations

Soon will be listed here.

Abstract

Background: We have developed a new approach to reduce the serum interference for ELISA. The purpose of this study is to investigate if we can use the optimized ELISA (MBB-ELISA) to detect serum soluble HER2/neu (sHER2) in early stage primary breast cancer and monitor its change during treatments.

Findings: We collected sera preoperatively from 118 primary breast cancer patients. Serum samples were also collected sequentially from a subset of patients during and after adjuvant treatment. sHER2 in these samples was measured by the MBB-ELISA. Only 16.7 % of tissue HER2 (tHER2) positive patients had significantly elevated sHER2 levels in serum. Interestingly, sera of some patients with tHER2 negative tumors, including those that were 2+ by IHC but negative by FISH, demonstrated slightly elevated sHER2 levels. Multivariate analysis demonstrated that patients with elevated sHER2 (> = 7 ng/ml) had significantly worse disease free survival. During treatments, sHER2 levels consistently fell in response to adjuvant therapies. Nevertheless, in all 4 patients who developed metastases, a steady rise in sHER2 levels was noted before metastatic disease became clinically evident.

Conclusions: For early stage breast cancers, sHER2 is a poor biomarker to predict tHER2 status, but may have value to supplement tissue tests to identify patients with HER2 tumors. Our results also suggest that sHER2 is worth further study as a biomarker to monitor breast cancer patients during treatments.

Citing Articles

Review of the AlGaN/GaN High-Electron-Mobility Transistor-Based Biosensors: Structure, Mechanisms, and Applications.

Li C, Chen X, Wang Z Micromachines (Basel). 2024; 15(3).

PMID: 38542577 PMC: 10972248. DOI: 10.3390/mi15030330.

Prognostic Value of the Serum HER2 Extracellular Domain Level in Breast Cancer: A Systematic Review and Meta-Analysis.

Wu Y, Li L, Zhang D, Ma F Cancers (Basel). 2022; 14(19).

PMID: 36230471 PMC: 9559205. DOI: 10.3390/cancers14194551.

Circulating proteins as predictive and prognostic biomarkers in breast cancer.

Veyssiere H, Bidet Y, Penault-Llorca F, Radosevic-Robin N, Durando X Clin Proteomics. 2022; 19(1):25.

PMID: 35818030 PMC: 9275040. DOI: 10.1186/s12014-022-09362-0.

On Demand Biosensors for Early Diagnosis of Cancer and Immune Checkpoints Blockade Therapy Monitoring from Liquid Biopsy.

Mummareddy S, Pradhan S, Narasimhan A, Natarajan A Biosensors (Basel). 2021; 11(12).

PMID: 34940257 PMC: 8699359. DOI: 10.3390/bios11120500.

Serum HER2 levels predict treatment efficacy and prognosis in patients with HER2-positive breast cancer undergoing neoadjuvant treatment.

Zuo W, He M, Zheng H, Liu Y, Liu X, Jiang Y Gland Surg. 2021; 10(4):1300-1314.

PMID: 33968682 PMC: 8102211. DOI: 10.21037/gs-20-802.

References

Zhang H, Kacharmina J, Miyashiro K, Greene M, Eberwine J . Protein quantification from complex protein mixtures using a proteomics methodology with single-cell resolution. Proc Natl Acad Sci U S A. 2001; 98(10):5497-502. PMC: 33241. DOI: 10.1073/pnas.101124598. View

Lam L, Czerniecki B, Fitzpatrick E, Xu S, Schuchter L, Xu X . Interference-Free HER2 ECD as a Serum Biomarker in Breast Cancer. J Mol Biomark Diagn. 2014; 4(3):151. PMC: 4114390. DOI: 10.4172/2155-9929.1000151. View

Barok M, Tanner M, Koninki K, Isola J . Trastuzumab-DM1 causes tumour growth inhibition by mitotic catastrophe in trastuzumab-resistant breast cancer cells in vivo. Breast Cancer Res. 2011; 13(2):R46. PMC: 3219209. DOI: 10.1186/bcr2868. View

Esteva F, Cheli C, Fritsche H, Fornier M, Slamon D, Thiel R . Clinical utility of serum HER2/neu in monitoring and prediction of progression-free survival in metastatic breast cancer patients treated with trastuzumab-based therapies. Breast Cancer Res. 2005; 7(4):R436-43. PMC: 1175054. DOI: 10.1186/bcr1020. View

Christianson T, DOHERTY J, Lin Y, Ramsey E, Holmes R, Keenan E . NH2-terminally truncated HER-2/neu protein: relationship with shedding of the extracellular domain and with prognostic factors in breast cancer. Cancer Res. 1998; 58(22):5123-9. View

Lee S, Lee J, Yu J, Ko B, Kim H, Son B . Preoperative serum HER2 extracellular domain levels in primary invasive breast cancer. BMC Cancer. 2014; 14:929. PMC: 4295268. DOI: 10.1186/1471-2407-14-929. View

Potts S, Krueger J, Landis N, Eberhard D, Young G, Schmechel S . Evaluating tumor heterogeneity in immunohistochemistry-stained breast cancer tissue. Lab Invest. 2012; 92(9):1342-57. DOI: 10.1038/labinvest.2012.91. View

Zhang H, Cheng X, Richter M, Greene M . A sensitive and high-throughput assay to detect low-abundance proteins in serum. Nat Med. 2006; 12(4):473-7. DOI: 10.1038/nm1378. View

Zhang H, Berezov A, Wang Q, Zhang G, Drebin J, Murali R . ErbB receptors: from oncogenes to targeted cancer therapies. J Clin Invest. 2007; 117(8):2051-8. PMC: 1934579. DOI: 10.1172/JCI32278. View

10.

Zhang H, Fu T, McGettigan S, Kumar S, Liu S, Speicher D . IL-8 and cathepsin B as melanoma serum biomarkers. Int J Mol Sci. 2011; 12(3):1505-18. PMC: 3111615. DOI: 10.3390/ijms12031505. View

11.

Colomer R, Montero S, Lluch A, Ojeda B, Barnadas A, Casado A . Circulating HER2 extracellular domain and resistance to chemotherapy in advanced breast cancer. Clin Cancer Res. 2000; 6(6):2356-62. View

12.

Franklin M, Carey K, Vajdos F, Leahy D, de Vos A, Sliwkowski M . Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell. 2004; 5(4):317-28. DOI: 10.1016/s1535-6108(04)00083-2. View

13.

Slamon D, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A . Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001; 344(11):783-92. DOI: 10.1056/NEJM200103153441101. View

14.

Liu P, Liu X, Li Y, Covington M, Wynn R, Huber R . Identification of ADAM10 as a major source of HER2 ectodomain sheddase activity in HER2 overexpressing breast cancer cells. Cancer Biol Ther. 2006; 5(6):657-64. DOI: 10.4161/cbt.5.6.2708. View

15.

Tse C, Gauchez A, Jacot W, Lamy P . HER2 shedding and serum HER2 extracellular domain: biology and clinical utility in breast cancer. Cancer Treat Rev. 2011; 38(2):133-42. DOI: 10.1016/j.ctrv.2011.03.008. View

16.

Moreno-Aspitia A, Hillman D, Dyar S, Tenner K, Gralow J, Kaufman P . Soluble human epidermal growth factor receptor 2 (HER2) levels in patients with HER2-positive breast cancer receiving chemotherapy with or without trastuzumab: results from North Central Cancer Treatment Group adjuvant trial N9831. Cancer. 2013; 119(15):2675-82. PMC: 4126833. DOI: 10.1002/cncr.28130. View

17.

Ludovini V, Gori S, Colozza M, Pistola L, Rulli E, Floriani I . Evaluation of serum HER2 extracellular domain in early breast cancer patients: correlation with clinicopathological parameters and survival. Ann Oncol. 2008; 19(5):883-90. DOI: 10.1093/annonc/mdm585. View

18.

Papoian R . Non-specific immunoglobulin interactions may lead to false-positive results in assays for human anti-mouse monoclonal antibodies (HAMA). J Immunoassay. 1992; 13(2):289-96. DOI: 10.1080/15321819208021232. View

19.

Cai Z, Zhang G, Zhou Z, Bembas K, Drebin J, Greene M . Differential binding patterns of monoclonal antibody 2C4 to the ErbB3-p185her2/neu and the EGFR-p185her2/neu complexes. Oncogene. 2008; 27(27):3870-4. PMC: 2819401. DOI: 10.1038/onc.2008.13. View

20.

Lam L, McAndrew N, Yee M, Fu T, Tchou J, Zhang H . Challenges in the clinical utility of the serum test for HER2 ECD. Biochim Biophys Acta. 2012; 1826(1):199-208. PMC: 3362659. DOI: 10.1016/j.bbcan.2012.03.012. View