Serum NSE, MMP‐9 and HER2 extracellular domain are associated with brain metastases in metastatic breast cancer patients: predictive biomarkers for brain metastases?

• Published in: International journal of cancer 2016-11, Vol.139 (10), p.2299-2311
• Main Authors: Darlix, Amélie, Lamy, Pierre‐Jean, Lopez‐Crapez, Evelyne, Braccini, Antoine Laurent, Firmin, Nelly, Romieu, Gilles, Thézenas, Simon, Jacot, William
• Format: Article
• Language: English
• Subjects: Aged; Biomarkers; Biomarkers, Tumor; Biomarkers, Tumor - blood; Brain cancer; brain metastases; Brain Neoplasms; Brain Neoplasms - blood; Brain Neoplasms - enzymology; Brain Neoplasms - secondary; Breast cancer; Breast Neoplasms; Breast Neoplasms - blood; Breast Neoplasms - enzymology; Breast Neoplasms - pathology; Cancer; Case-Control Studies; Central nervous system; Chemotherapy; ErbB-2 protein; Female; Human health and pathology; Humans; Life Sciences; Matrix metalloproteinase; Matrix Metalloproteinase 9; Matrix Metalloproteinase 9 - blood; Medical research; Metalloproteinase; Metastases; Metastasis; Middle Aged; Multivariate analysis; Phosphopyruvate Hydratase; Phosphopyruvate Hydratase - blood; Receptor, ErbB-2; Receptor, ErbB-2 - blood; Retrospective Studies; Risk factors; S100 Calcium Binding Protein beta Subunit; S100 Calcium Binding Protein beta Subunit - blood; Serum levels; Tropism; Tumor markers; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.30290

Breast cancer (BC) is the second most common cause of brain metastases (BM). Predictive factors for BM have been widely studied in metastatic BC; however, there is no known serum tumor marker to accurately predict BM. Elevated serum S100ß protein and neuron‐specific enolase (NSE) could reflect the brain damages induced by BM. Matrix metalloproteinase 9 (MMP‐9) is involved in tumor invasion and metastatic dissemination, including BM. Also, HER2‐amplified BC were shown to have a particular tropism for central nervous system (CNS). This study evaluated the correlation of these biomarkers with the presence of BM in metastatic BC patients. In this case‐control study, 88 consecutive metastatic BC patients with BM (BM group) treated in our institution (2008–2015) were retrospectively selected, based on the availability of frozen serum samples for tumor marker determination. Patients were matched by age, tumor biology and number of previous metastatic chemotherapy lines to 162 metastatic BC patients without CNS involvement (control group). Serum NSE, MMP‐9 and HER2 extracellular domain (ECD) levels were significantly higher in the BM group (p = 0.0051, p = 0.0062 and p = 0.0057, respectively). In multivariate analysis, serum HER2 and MMP‐9 levels accurately discriminated patients with BM: odds ratios 4.4 (p < 0.001; 95%CI: 1.9–9.6) for HER2 ECD and 3.5 (p = 0.005; 95%CI: 1.5–8.4) for MMP‐9. In multivariate analysis, HER2 ECD and NSE serum levels were independent prognostic factors in patients with BM. Serum HER2 ECD and MMP‐9 appear to be associated with BM in metastatic BC patients. Their predictive value for BM still needs to be evaluated in further prospective studies. What's new? Despite extensive research on predictive factors for brain metastases in breast cancer patients, markers capable of accurately detecting brain metastases before symptoms appear are lacking. The authors of the present study set out to address this problem by investigating the value of multiple serum biomarkers in metastatic breast cancer patients with or without brain metastases. They found that levels of three markers—serum neuron‐specific enolase (NSE), matrix metalloproteinase‐9 (MMP‐9) and human epidermal growth factor receptor 2 (HER2) extracellular domain (ECD)—were associated specifically with brain metastases. Elevated NSE and HER2 ECD and low S100ß levels were independent determinants of poor prognosis.