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Br J Cancer. 2012 Nov 20;107(11):1892-900. doi: 10.1038/bjc.2012.475. Epub 2012 Oct 18.

Thymosin beta 15A (TMSB15A) is a predictor of chemotherapy response in triple-negative breast cancer.

Author information

1
Institute of Pathology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. silvia.darb-esfahani@charite.de

Abstract

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.

CONCLUSION:

In TNBC, TMSB15A gene expression analysis might help to select patients with a high chance for pCR after NACT.

PMID:
23079573
PMCID:
PMC3504944
DOI:
10.1038/bjc.2012.475
[Indexed for MEDLINE]
Free PMC Article

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