Thymosin beta 15A (TMSB15A) is a predictor of chemotherapy response in triple-negative breast cancer.
BACKGROUND
Biomarkers predictive of pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) of breast cancer are urgently needed.


METHODS
Using a training/validation approach for detection of predictive biomarkers in HER2-negative breast cancer, pre-therapeutic core biopsies from four independent cohorts were investigated: Gene array data were analysed in fresh frozen samples of two cohorts (n=86 and n=55). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed in formalin-fixed, paraffin-embedded (FFPE) samples from two neoadjuvant phase III trials (GeparTrio, n=212, and GeparQuattro, n=383).


RESULTS
A strong predictive capacity of thymosin beta 15 (TMSB15A) gene expression was evident in both fresh frozen cohorts (P<0.0001; P<0.0042). In the GeparTrio FFPE training cohort, a significant linear correlation between TMSB15A expression and pCR was apparent in triple-negative breast cancer (TNBC) (n=61, P=0.040). A cutoff point was then defined that divided TNBC into a low and a high expression group (pCR rate 16.0% vs 47.2%). Both linear correlation of TMSB15A mRNA levels (P=0.017) and the pre-defined cutoff point were validated in 134 TNBC from GeparQuattro (pCR rate 36.8% vs 17.0%, P=0.020). No significant predictive capacity was observed in luminal carcinomas from GeparTrio and GeparQuattro.


CONCLUSIONS
In TNBC, TMSB15A gene expression analysis might help to select patients with a high chance for pCR after NACT.
Institute of Pathology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. silvia.darb-esfahani@charite.de
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Darb-Esfahani
R
R
Kronenwett
G
G
von Minckwitz
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C
Denkert
M
M
Gehrmann
A
A
Rody
J
J
Budczies
J C
JC
Brase
M K
MK
Mehta
H
H
Bojar
B
B
Ataseven
T
T
Karn
E
E
Weiss
D M
DM
Zahm
F
F
Khandan
M
M
Dietel
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Loibl
D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D017326:Clinical Trials, Phase III as Topic; D047628:Estrogen Receptor alpha / Q000032:analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016015:Logistic Models; D012333:RNA, Messenger / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013947:Thymosin / Q000235:genetics*
D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; D013947:Thymosin; C506487:ESR1 protein, human; C508053:ERBB2 protein, human