Predicting early brain metastases based on clinicopathological factors and gene expression analysis in advanced HER2-positive breast cancer patients

• Published in: Journal of neuro-oncology 2015-03, Vol.122 (1), p.205-216
• Main Authors: Duchnowska, Renata, Jassem, Jacek, Goswami, Chirayu Pankaj, Dundar, Murat, Gökmen-Polar, Yesim, Li, Lang, Woditschka, Stephan, Biernat, Wojciech, Sosińska-Mielcarek, Katarzyna, Czartoryska-Arłukowicz, Bogumiła, Radecka, Barbara, Tomasevic, Zorica, Stępniak, Piotr, Wojdan, Konrad, Sledge, George W., Steeg, Patricia S., Badve, Sunil
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biomarkers, Tumor - genetics; Brain Neoplasms - genetics; Brain Neoplasms - mortality; Brain Neoplasms - secondary; Brain Neoplasms - therapy; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Carcinoma, Ductal, Breast - genetics; Carcinoma, Ductal, Breast - mortality; Carcinoma, Ductal, Breast - secondary; Carcinoma, Ductal, Breast - therapy; Carcinoma, Lobular - genetics; Carcinoma, Lobular - mortality; Carcinoma, Lobular - secondary; Carcinoma, Lobular - therapy; Clinical Study; Cohort Studies; Combined Modality Therapy; Female; Follow-Up Studies; Gene Expression Profiling; Humans; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Grading; Neoplasm Staging; Neurology; Oligonucleotide Array Sequence Analysis; Oncology; Prognosis; Real-Time Polymerase Chain Reaction; Receptor, ErbB-2 - genetics; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Survival Rate
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-014-1704-y

The overexpression or amplification of the human epidermal growth factor receptor 2 gene ( HER2 / neu ) is associated with high risk of brain metastasis (BM). The identification of patients at highest immediate risk of BM could optimize screening and facilitate interventional trials. We performed gene expression analysis using complementary deoxyribonucleic acid-mediated annealing, selection, extension and ligation and real-time quantitative reverse transcription PCR (qRT-PCR) in primary tumor samples from two independent cohorts of advanced HER2 positive breast cancer patients. Additionally, we analyzed predictive relevance of clinicopathological factors in this series. Study group included discovery Cohort A (84 patients) and validation Cohort B (75 patients). The only independent variables associated with the development of early BM in both cohorts were the visceral location of first distant relapse [Cohort A: hazard ratio (HR) 7.4, 95 % CI 2.4–22.3; p