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


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.


CONCLUSIONS
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.
Department of Oncology, Military Institute of Medicine, Warsaw, Poland. Electronic address: rdtt@wp.pl.
Renata
R
Duchnowska
3rd Department of Radiotherapy and Chemotherapy, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Michał
M
Jarząb
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.
Jadwiga
J
Żebracka-Gala
Department of Oncology, Wroclaw Medical University, Wrocław, Poland.
Rafał
R
Matkowski
Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland.
Anna
A
Kowalczyk
Department of Oncology, Oncology Center, Opole, Poland.
Barbara
B
Radecka
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.
Małgorzata
M
Kowalska
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.
Aleksandra
A
Pfeifer
Department of Oncology, West Pomeranian Oncology Center, Szczecin, Poland.
Małgorzata
M
Foszczyńska-Kłoda
Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
Antonino
A
Musolino
Department of Oncology, Oncology Center, Białystok, Poland.
Bogumiła
B
Czartoryska-Arłukowicz
Department of Oncology, Greater Poland Cancer Center, Poznań, Poland.
Maria
M
Litwiniuk
Department of Oncology, Warmia and Masuria Oncology Center, Olsztyn, Poland.
Anna
A
Surus-Hyla
Department of Oncology, Silesian Medical University, Katowice, Poland.
Sylwia
S
Szabłowska-Siwik
Department of Oncology, Regional Oncology Center, Rzeszów, Poland.
Bożenna
B
Karczmarek-Borowska
Department of Oncology, Medical University of Łódź, Łódź, Poland.
Sylwia
S
Dębska-Szmich
Department of Oncology, Regional Hospital, Radom, Poland.
Beata
B
Głodek-Sutek
Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland.
Katarzyna
K
Sosińska-Mielcarek
Department of Oncology, Oncology Center, Bydgoszcz, Poland.
Ewa
E
Chmielowska
Department of Oncology, Regional Oncology Center, Łódź, Poland.
Ewa
E
Kalinka-Warzocha
Department of Pathology and Laboratory Diagnostic, Oncology Center-Institute, Warsaw, Poland.
Wojciech P
WP
Olszewski
Department of Pathology, Military Institute of Medicine, Warsaw, Poland.
Janusz
J
Patera
Department of Pathology, Medical University of Gdańsk, Gdańsk, Poland.
Anton
A
Żawrocki
Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland.
Agnieszka
A
Pliszka
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.
Tomasz
T
Tyszkiewicz
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.
Dagmara
D
Rusinek
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.
Małgorzata
M
Oczko-Wojciechowska
Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland.
Jacek
J
Jassem
Department of Pathology, Medical University of Gdańsk, Gdańsk, Poland.
Wojciech
W
Biernat
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000556:secondary; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000473:pathology
D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; C506487:ESR1 protein, human; C508053:ERBB2 protein, human
Brain metastasis; Selection; Transcriptomic profiling; Triple negative breast cancer; cDNA-mediated annealing, extension, and ligation (DASL) assay