TY - JOUR
T1 - Thymosin beta 15A (TMSB15A) is a predictor of chemotherapy response in triple-negative breast cancer
AU - Darb-Esfahani, S.
AU - Kronenwett, R.
AU - Von Minckwitz, G.
AU - Denkert, C.
AU - Gehrmann, M.
AU - Rody, A.
AU - Budczies, J.
AU - Brase, J. C.
AU - Mehta, M. K.
AU - Bojar, H.
AU - Ataseven, B.
AU - Karn, T.
AU - Weiss, E.
AU - Zahm, D. M.
AU - Khandan, F.
AU - Dietel, M.
AU - Loibl, S.
PY - 2012/11/20
Y1 - 2012/11/20
N2 - 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 (n86 and n55). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed in formalin-fixed, paraffin-embedded (FFPE) samples from two neoadjuvant phase III trials (GeparTrio, n212, and GeparQuattro, n383).Results:A strong predictive capacity of thymosin beta 15 (TMSB15A) gene expression was evident in both fresh frozen cohorts (P0.0001; P0.0042). In the GeparTrio FFPE training cohort, a significant linear correlation between TMSB15A expression and pCR was apparent in triple-negative breast cancer (TNBC) (n61, P0.040). 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 (P0.017) and the pre-defined cutoff point were validated in 134 TNBC from GeparQuattro (pCR rate 36.8% vs 17.0%, P0.020). No significant predictive capacity was observed in luminal carcinomas from GeparTrio and GeparQuattro.Conclusion:In TNBC, TMSB15A gene expression analysis might help to select patients with a high chance for pCR after NACT.
AB - 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 (n86 and n55). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed in formalin-fixed, paraffin-embedded (FFPE) samples from two neoadjuvant phase III trials (GeparTrio, n212, and GeparQuattro, n383).Results:A strong predictive capacity of thymosin beta 15 (TMSB15A) gene expression was evident in both fresh frozen cohorts (P0.0001; P0.0042). In the GeparTrio FFPE training cohort, a significant linear correlation between TMSB15A expression and pCR was apparent in triple-negative breast cancer (TNBC) (n61, P0.040). 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 (P0.017) and the pre-defined cutoff point were validated in 134 TNBC from GeparQuattro (pCR rate 36.8% vs 17.0%, P0.020). No significant predictive capacity was observed in luminal carcinomas from GeparTrio and GeparQuattro.Conclusion:In TNBC, TMSB15A gene expression analysis might help to select patients with a high chance for pCR after NACT.
UR - http://www.scopus.com/inward/record.url?scp=84870062553&partnerID=8YFLogxK
U2 - 10.1038/bjc.2012.475
DO - 10.1038/bjc.2012.475
M3 - Journal articles
C2 - 23079573
AN - SCOPUS:84870062553
SN - 0007-0920
VL - 107
SP - 1892
EP - 1900
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 11
ER -
