e21000 Background: The human epidermal growth factor receptor (EGFR/HER) gene family encodes four homologous tyrosine kinases that regulate cell growth and proliferation, survival, motility, and adhesion. HER2 gene amplification and receptor overexpression have been observed in < 20% of non-small cell lung cancers (NSCLC). Serum concentrations of soluble HER2 (sHER2), a proteolytic fragment of the receptor’s extracellular domain, have been associated with tumor HER2 overexpression, advanced stage, and high grade. This study evaluated serum sHER2 as a prognostic biomarker of NSCLC. Methods: Patients with primary NSCLC (n=149) were recruited at the University of Kentucky prospectively between 2002 and 2008 by the Markey Cancer Center Biospecimen Core Program and linked to the Kentucky Cancer Registry - a population-based cancer registry of the NCI Surveillance, Epidemiology and End Results (SEER) Program - to obtain clinicopathological data. Serum samples were collected prior to surgery and quantified to determine sHER2 concentrations by sp185HER-2 ELISA (Bender MedSystems Diagnostics GmbH). Non-parametric tests were performed to assess whether sHER2 concentrations differed between NSCLC patients stratified by gender, stage, histology, and grade. Cox regression analyses were performed to assess whether sHER2 concentrations, age, gender, stage, histology, and grade are associated with progression free and overall survival. Results: Mean patient age in this case series is 62 years (SD = 10.84 years) and median overall survival is 30 months. Over 97% of patients are smokers. Although serum concentrations do not differ between males and females (p = 0.12), high sHER2 concentrations portend a 72% lower relative risk of death (H.R. = 0.283, p = 0.009) and longer overall survival among men, but not among women (H.R. = 1.012, p = 0.965) adjusted for stage. Conclusions: The results show that low serum sHER2 concentration is an adverse prognosticator of overall survival in males, but not females, and suggest that low serum sHER2 could be useful for stratifying male NSCLC patients for HER2-targeted therapy. Further investigation is warranted to assess sHER2 as a gender dependent prognostic (and potential theragnostic) biomarker of NSCLC.
Metastatic breast cancer to the leptomeninges is a late event in the disease course and is associated with significant morbidity and a grave prognosis. Treatment typically involves direct intrathecal injection of chemotherapy into the cerebrospinal fluid compartment since systemic chemotherapy penetrates poorly to the central nervous system. Here we report an interesting clinical observation involving a patient presenting with leptomeningeal spread of breast cancer causing extensive spinal cord compression with obliteration of the subarachnoid space, thus precluding the use of direct intrathecal chemotherapy. We administered systemic chemotherapy using weekly docetaxel with complete radiographic resolution of her disease and recovery from clinical spinal cord compression. While this is a single clinical observation, weekly administration of docetaxel in this circumstance may have been associated with improved drug "escape" into the central nervous system and better antitumor effect. Because leptomeningeal disease is typically a late event in metastatic breast cancer, resistance to therapeutic intervention may reflect intrinsically resistant disease in the setting of extensive prior therapy rather than a routine problem with systemic drug delivery to the CNS. Studying patterns of disease relapse in patients who had received adjuvant weekly taxanes may provide insights into this hypothesis.
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