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Clin Breast Cancer. 2017 Apr;17(2):e65-e75. doi: 10.1016/j.clbc.2016.08.008. Epub 2016 Sep 8.

Brain Metastasis Prediction by Transcriptomic Profiling in Triple-Negative Breast Cancer.

Author information

1
Department of Oncology, Military Institute of Medicine, Warsaw, Poland. Electronic address: rdtt@wp.pl.
2
3rd Department of Radiotherapy and Chemotherapy, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
3
Laboratory of Molecular Diagnostics and Functional Genomics, Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
4
Department of Oncology, Wroclaw Medical University, Wrocław, Poland.
5
Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland.
6
Department of Oncology, Oncology Center, Opole, Poland.
7
Department of Oncology, West Pomeranian Oncology Center, Szczecin, Poland.
8
Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
9
Department of Oncology, Oncology Center, Białystok, Poland.
10
Department of Oncology, Greater Poland Cancer Center, Poznań, Poland.
11
Department of Oncology, Warmia and Masuria Oncology Center, Olsztyn, Poland.
12
Department of Oncology, Silesian Medical University, Katowice, Poland.
13
Department of Oncology, Regional Oncology Center, Rzeszów, Poland.
14
Department of Oncology, Medical University of Łódź, Łódź, Poland.
15
Department of Oncology, Regional Hospital, Radom, Poland.
16
Department of Oncology, Oncology Center, Bydgoszcz, Poland.
17
Department of Oncology, Regional Oncology Center, Łódź, Poland.
18
Department of Pathology and Laboratory Diagnostic, Oncology Center-Institute, Warsaw, Poland.
19
Department of Pathology, Military Institute of Medicine, Warsaw, Poland.
20
Department of Pathology, Medical University of Gdańsk, Gdańsk, Poland.

Abstract

BACKGROUND:

Triple-negative breast cancer (TNBC) lacks expression of steroid hormone receptors (estrogen receptor α and progesterone) and epidermal growth factor receptor type 2. This phenotype shows high metastatic potential, with particular predilection to lungs and brain. Determination of TNBC transcriptomic profiles associated with high risk of brain metastasis (BM) might identify patients requiring alternative, more aggressive, or specific preventive and therapeutic approaches.

PATIENTS AND METHODS:

Using a cDNA-mediated annealing, selection, extension, and ligation assay, we investigated expression of 29,369 gene transcripts in primary TNBC tumor samples from 119 patients-71 in discovery cohort A and 48 in independent cohort B-that included best discriminating genes. Expression of mRNA was correlated with the occurrence of symptomatic BM.

RESULTS:

In cohort A, the difference at the noncorrected P < .005 was found for 64 transcripts (P = .23 for global test), but none showed significant difference at a preset level of false-discovery rate of < 10%. Of the 30 transcripts with the largest differences between patients with and without BM in cohort A, none was significantly associated with BM in cohort B.

CONCLUSION:

Analysis based on the primary tumor gene transcripts alone is unlikely to predict BM development in advanced TNBC. Despite its negative findings, the study adds to the knowledge on the biology of TNBC and paves the way for future projects using more advanced molecular assays.

KEYWORDS:

Brain metastasis; Selection; Transcriptomic profiling; Triple negative breast cancer; cDNA-mediated annealing, extension, and ligation (DASL) assay

PMID:
27692773
DOI:
10.1016/j.clbc.2016.08.008
[Indexed for MEDLINE]

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