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Validation of the 18-gene classifier as a prognostic biomarker of distant metastasis in breast cancer.

Validation of the 18-gene classifier as a prognostic biomarker of distant metastasis in breast cancer.
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Cheng SH, Huang TT, Cheng YH, Tan TBK, Horng CF, Wang YA, Brian NS, Shih LS, Yu BL,


Cheng SH, Huang TT, Cheng YH, Tan TBK, Horng CF, Wang YA, Brian NS, Shih LS, Yu BL, (click to view)

Cheng SH, Huang TT, Cheng YH, Tan TBK, Horng CF, Wang YA, Brian NS, Shih LS, Yu BL,

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PloS one 2017 09 0812(9) e0184372 doi 10.1371/journal.pone.0184372
Abstract

We validated an 18-gene classifier (GC) initially developed to predict local/regional recurrence after mastectomy in estimating distant metastasis risk. The 18-gene scoring algorithm defines scores as: <21, low risk; ≥21, high risk. Six hundred eighty-three patients with primary operable breast cancer and fresh frozen tumor tissues available were included. The primary outcome was the 5-year probability of freedom from distant metastasis (DMFP). Two external datasets were used to test the predictive accuracy of 18-GC. The 5-year rates of DMFP for patients classified as low-risk (n = 146, 21.7%) and high-risk (n = 537, 78.6%) were 96.2% (95% CI, 91.1%-98.8%) and 80.9% (74.6%-81.9%), respectively (median follow-up interval, 71.8 months). The 5-year rates of DMFP of the low-risk group in stage I (n = 62, 35.6%), stage II (n = 66, 20.1%), and stage III (n = 18, 10.3%) were 100%, 94.2% (78.5%-98.5%), and 90.9% (50.8%-98.7%), respectively. Multivariate analysis revealed that 18-GC is an independent prognostic factor of distant metastasis (adjusted hazard ratio, 5.1; 95% CI, 1.8-14.1; p = 0.0017) for scores of ≥21. External validation showed that the 5-year rate of DMFP in the low- and high-risk patients was 94.1% (82.9%-100%) and 80.3% (70.7%-89.9%, p = 0.06) in a Singapore dataset, and 89.5% (81.9%-94.1%) and 73.6% (67.2%-79.0%, p = 0.0039) in the GEO-GSE20685 dataset, respectively. In conclusion, 18-GC is a viable prognostic biomarker for breast cancer to estimate distant metastasis risk.

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