32P - Molecular characterization of breast cancer brain metastases and circulating tumor cells

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Breast Cancer, Metastatic
Pathology/Molecular Biology
Translational Research
Presenter Harriet Wikman
Citation Annals of Oncology (2015) 26 (suppl_3): 10-14. 10.1093/annonc/mdv116
Authors H. Wikman1, I. Hohensee2, C. Riebensahm2, I. Witzel3, J. Matschke4, M. Glatzel4, K. Lamszus5, S. Riehtdorf2, V. Müller6, K. Pantel2
  • 1Tumor Biology, UKE Universitätsklinikum Hamburg-Eppendorf KMTZ, 20246 Hamburg - Hamburg/DE
  • 2Tumor Biology, UKE Universitätsklinikum Hamburg-Eppendorf KMTZ, Hamburg/DE
  • 3Department Of Gynecology, UKE Universitätsklinikum Hamburg-Eppendorf KMTZ, Hamburg/DE
  • 4Neuropathology, UKE Universitätsklinikum Hamburg-Eppendorf KMTZ, Hamburg/DE
  • 5Department Of Neurosurgery, UKE Universitätsklinikum Hamburg-Eppendorf KMTZ, 20246 - Hamburg/DE
  • 6Department Of Gynecology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg - Hamburg/DE

Abstract

Body

Background: With the improvement of therapeutic options for the treatment of metastatic breast cancer, the development of brain metastases has become a major limitation of life expectancy for many breast cancer patients. As the tumor may evolve and gain new molecular changes during the metastatic cascade, our aim has been to molecularly characterize both the brain metastases as well as the circulating tumor cells (CTCs) in breast cancer patients.

Methods: We first screened both primary and metastatic breast tumors by way of expressional and copy number profiling in order to identify potential new markers and targets for brain metastasis. The identified main pathway alterations were verified by immunohistochemistry on brain metastases TMAs. Furthermore, the blood from brain metastases patients was screened for CTCs.

Results: We have been able to identify genetic alterations in the primary breast tumors associated with metastatic spread to the brain. Most importantly we found that there are two major pathways (EGFR and HER2) driving brain metastasis. Almost all patients (91%) suffering from brain metastases with a triple-negative (TNBC) tumor have either a gain of EGFR or a loss of PTEN, whereas amplification of HER2 with concurrent EGFR alteration is only found in 5.7% of all brain metastases. Whereas EGFR alterations could be found in only 7% of hormone receptor positive tumors, loss of PTEN was found in 23%. These markers can also be used for identifying and for subclassifying CTCs from patients. The heterogeneity of EGFR and HER2 expression seem to be larger in CTCs.

Conclusions: Our results imply that almost all patients with brain metastases have an abnormal HER2/EFGR signaling pathway caused by partially mutually exclusive alterations. In order to obtain more specific insights into the molecular alterations of brain metastases and to define subgroups of patients, who potentially could benefit from novel targeted therapies, we are currently characterizing CTCs from these patients and perform functional analyses on single genes involved in these processes.

Disclosure: All authors have declared no conflicts of interest.