Changing molecular profile of brain metastases compared with matched breast primary cancers and impact on clinical outcomes
Open Access
- 23 February 2016
- journal article
- research article
- Published by Springer Science and Business Media LLC in British Journal of Cancer
- Vol. 114 (7), 793-800
- https://doi.org/10.1038/bjc.2016.34
Abstract
Breast cancer commonly metastasises to the brain, but little is known about changes in the molecular profile of the brain secondaries and impact on clinical outcomes. Patients with samples from brain metastases and matched breast cancers were included. Immunohistochemical analysis for oestrogen receptor, progesterone receptor, p27kip1, cyclin D1, epidermal growth factor receptor, insulin like growth factor 1, insulin like growth factor 1 receptor, vascular endothelial growth factor A, transforming growth factor-β and HER2 receptor was performed. Borderline HER2 results were analysed by fluorescent in situ hybridisation. Levels of expression were compared, with review of effect on clinical outcomes. A total of 41 patients were included. Of the patients, 20% had a change in oestrogen receptor or HER2 in their brain metastasis that could affect therapeutic decisions. There were statistically significant rises in brain metastases for p27kip1 (P=0.023) and cyclin D1 (P=0.030) and a fall in vascular endothelial growth factor A (P=0.012). Overall survival from the time of metastasis increased significantly with oestrogen receptor-positive (P=0.005) and progesterone receptor-positive (P=0.013) brain lesions and with a longer duration from diagnosis of the breast primary (P<0.001). In this cohort there were phenotypic differences in metastatic brain tumours compared with matched primary breast tumours. These could be relevant for aetiology, and have an impact on prognostication, current and future therapies.Keywords
This publication has 73 references indexed in Scilit:
- The expression and significance of insulin-like growth factor-1 receptor and its pathway on breast cancer stem/progenitorsBreast Cancer Research, 2013
- Biomarker results from the AVADO phase 3 trial of first-line bevacizumab plus docetaxel for HER2-negative metastatic breast cancerBritish Journal of Cancer, 2013
- Combined targeting of HER2 and VEGFR2 for effective treatment ofHER2-amplified breast cancer brain metastasesProceedings of the National Academy of Sciences of the United States of America, 2012
- Increased signalling of EGFR and IGF1R, and deregulation of PTEN/PI3K/Akt pathway are related with trastuzumab resistance in HER2 breast carcinomasBritish Journal of Cancer, 2012
- Changes in the ER, PgR, HER2, p53 and Ki-67 biological markers between primary and recurrent breast cancer: discordance rates and prognosisWorld Journal of Surgical Oncology, 2011
- Central Nervous System Metastases in Patients with HER2-Positive Metastatic Breast Cancer: Incidence, Treatment, and Survival in Patients from registHERClinical Cancer Research, 2011
- High levels of vascular endothelial growth factor and its receptors (VEGFR-1, VEGFR-2, neuropilin-1) are associated with worse outcome in breast cancerHuman Pathology, 2008
- Genetic Screening Reveals an Essential Role of p27kip1 in Restriction of Breast Cancer ProgressionCancer Research, 2007
- Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesisBritish Journal of Cancer, 2007
- A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast CancerThe New England Journal of Medicine, 2004