Abstract
BackgroundSerum levels of the extracellular domain of HER2/neu (HER2 ECD) have been demonstrated to be associated with clinical outcomes. A disintegrin and metalloproteinase-10, a sheddase of HER2/neu, can drive cancer progression and its activity is inhibited by tissue inhibitor of metalloproteinase-1 (TIMP-1). However, elevated TIMP-1 expression has been associated with a poor prognosis of breast cancer. Therefore, this study was performed to explore the relationships between serum HER2 ECD, TIMP-1 and clinical outcomes.MethodsOne hundred and eighty-five female breast cancer patients, who received curative mastectomy without neo-adjuvant chemotherapy at Chang-Gung Memorial Hospital, were recruited with informed consent for this study. Pre-operative serum levels of HER2 ECD and TIMP-1 were measured using an enzyme-linked immunosorbent assay.ResultsTwenty-three cases (12.4%) were classified HER2 ECD positive. HER2 ECD positivity was significantly associated with age, lymph node involvement, histological grade, estrogen receptor status, progesterone receptor status, tissue HER2/neu overexpression, and disease-free survival (DFS). In an age, stage, ER and HER2/neu status matched subgroup (N = 41), the serum level of TIMP-1 was significantly associated with HER2 ECD positivity and DFS.ConclusionsA high serum TIMP-1 was significantly associated with HER2 ECD positivity and a poorer DFS among Taiwanese primary breast cancer patients with HER2 overexpression.
Highlights
Serum levels of the extracellular domain of HER2/neu (HER2 ECD) have been demonstrated to be associated with clinical outcomes
Analysis of Serum HER2 ECD, matrix metalloproteinases (MMPs)-2, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and tissue inhibitors of metalloproteinases (TIMPs)-2 Serum was collected from the control individuals during their physical examination and from the breast cancer patients before surgery; the samples were stored at -70°C until they were assayed
High serum concentrations of HER2 ECD have been associated with HER2 overexpression [34], increased tumor burden [35], poorer survival [36] and resistance to endocrine therapy and chemotherapy [12,37,38], We found that HER2 ECD positivity was significantly associated with most clinicopathological parameters including tumor size, lymph node involvement, tumor stage, histological grade, chromosome ploidy, estrogen receptor status (ER), progesterone receptor status (PR), and HER2/neu membrane protein overexpression
Summary
Serum levels of the extracellular domain of HER2/neu (HER2 ECD) have been demonstrated to be associated with clinical outcomes. Amplification or overexpression of HER2/neu, a 185 kDa transmembrane tyrosine kinase receptor, has been reported in 20-30% of invasive breast cancers (IBCs) [1]. It predicts a more aggressive clinical course such as a transition from in situ growth to invasion [2], aggressive disease progression and poor treatment response [3,4,5]. Certain clinical studies have not supported baseline serum HER2 ECD as a reliable predictor of tumor progression, treatment response, duration of response, or time to progression in advanced/metastatic breast cancer [11,12]. In agreement with the 2007 and 2009 American Society of Clinical Oncology guidelines on the use of biomarkers in breast cancer [11,13], there is currently insufficient evidence to support the use of serum HER-2 ECD in the routine management of individual patients with breast cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
