Abstract
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.
Funder
National Institutes of Health
Abramson Cancer Center
McCabe Fellow Award
National Cancer Institute
the Linda and Paul Richardson Breast Cancer Research Funds
the Breast Cancer Immunotherapy Funds
2013 Exceptional Project Award from the Breast Cancer Alliance
Publisher
Springer Science and Business Media LLC
Reference20 articles.
1. Barok M, Tanner M, Koninki K, Isola J (2011) Trastuzumab-DM1 causes tumour growth inhibition by mitotic catastrophe in trastuzumab-resistant breast cancer cells in vivo. Breast Cancer Res 13(2):R46. doi:10.1186/bcr2868
2. Cai Z, Zhang G, Zhou Z, Bembas K, Drebin JA, Greene MI, Zhang H (2008) Differential binding patterns of monoclonal antibody 2C4 to the ErbB3-p185her2/neu and the EGFR-p185her2/neu complexes. Oncogene 27(27):3870–3874. doi:10.1038/onc.2008.13
3. Christianson TA, Doherty JK, Lin YJ, Ramsey EE, Holmes R, Keenan EJ, Clinton GM (1998) NH2-terminally truncated HER-2/neu protein: relationship with shedding of the extracellular domain and with prognostic factors in breast cancer. Cancer Res 58(22):5123–5129
4. Colomer R, Montero S, Lluch A, Ojeda B, Barnadas A, Casado A, Massuti B, Cortes-Funes H, Lloveras B (2000) Circulating HER2 extracellular domain and resistance to chemotherapy in advanced breast cancer. Clin Cancer Res 6(6):2356–2362
5. Esteva FJ, Cheli CD, Fritsche H, Fornier M, Slamon D, Thiel RP, Luftner D, Ghani F (2005) 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 7(4):R436–R443
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