Molecular characteristics and metastasis predictor genes of triple-negative breast cancer: a clinical study of triple-negative breast carcinomas.
BACKGROUND
Triple-negative breast cancer is a subtype of breast cancer with aggressive tumor behavior and distinct disease etiology. Due to the lack of an effective targeted medicine, treatment options for triple-negative breast cancer are few and recurrence rates are high. Although various multi-gene prognostic markers have been proposed for the prediction of breast cancer outcome, most of them were proven clinically useful only for estrogen receptor-positive breast cancers. Reliable identification of triple-negative patients with a favorable prognosis is not yet possible.


RESULTS
Clinicopathological information and microarray data from 157 invasive breast carcinomas were collected at National Taiwan University Hospital from 1995 to 2008. Gene expression data of 51 triple-negative and 106 luminal breast cancers were generated by oligonucleotide microarrays. Hierarchical clustering analysis revealed that the majority (94%) of triple-negative breast cancers were tightly clustered together carrying strong basal-like characteristics. A 45-gene prognostic signature giving 98% predictive accuracy in distant recurrence of our triple-negative patients was determined using the receiver operating characteristic analysis and leave-one-out cross validation. External validation of the prognostic signature in an independent microarray dataset of 59 early-stage triple-negative patients also obtained statistical significance (hazard ratio 2.29, 95% confidence interval (CI) 1.04-5.06, Cox P=0.04), outperforming five other published breast cancer prognostic signatures. The 45-gene signature identified in this study revealed that TGF-β signaling of immune/inflammatory regulation may play an important role in distant metastatic invasion of triple-negative breast cancer.


CONCLUSIONS
Gene expression data and recurrence information of triple-negative breast cancer were collected and analyzed in this study. A novel set of 45-gene signature was found to be statistically predictive in disease recurrence of triple-negative breast cancer. The 45-gene signature, if further validated, may be a clinically useful tool in risk assessment of distant recurrence for early-stage triple-negative patients.
Department of Surgery, College of Medicine, National Taiwan University, Taipei, Taiwan.
Wen-Hung
WH
Kuo
Yao-Yin
YY
Chang
Liang-Chuan
LC
Lai
Mong-Hsun
MH
Tsai
Chuhsing Kate
CK
Hsiao
King-Jen
KJ
Chang
Eric Y
EY
Chuang
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve