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pmid:28886126

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

Skye Hung-Chun Cheng · Tzu-Ting Huang · Yu-Hao Cheng · Tee Benita Kiat Tan · Chen-Fang Horng · Yong Alison Wang · Nicholas Shannon Brian · Li-Sun Shih · Ben-Long Yu

PloS one · 2017 doi:10.1371/journal.pone.0184372

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pmid:28886126
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title
Validation of the 18-gene classifier as a prognostic biomarker of distant metastasis in breast cancer.
doi
10.1371/journal.pone.0184372
pmid
28886126
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[0]
Skye Hung-Chun Cheng
[1]
Tzu-Ting Huang
[2]
Yu-Hao Cheng
[3]
Tee Benita Kiat Tan
[4]
Chen-Fang Horng
[5]
Yong Alison Wang
[6]
Nicholas Shannon Brian
[7]
Li-Sun Shih
[8]
Ben-Long Yu
journal
PloS one
year
2017
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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Cox proportional hazards regression models were used to assess the prognostic significance of age at diagnosis, primary tumor size, the number of axillary lymph nodes involved, tumor grade, lymphovascular invasion (LVI), ER/PR status, HER2 overexpression, breast cancer subtypes, and the 18-gene score (stratified by either a categorical factor or a continuous variable).
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sections[4] "Statistical methods" paragraph 2
quote
Cox proportional hazards regression models were used to assess the prognostic significance of age at diagnosis, primary tumor size, the number of axillary lymph nodes involved, tumor grade, lymphovascular invasion (LVI), ER/PR status, HER2 overexpression, breast cancer subtypes, and the 18-gene score (stratified by either a categorical factor or a continuous variable).
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We also used a dataset from GEO (GSE20685, ID: 200020685) from patients treated between 1991–2004
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Univariate and multivariate analyses of factors associated with distant metastasis based on Cox proportional hazards models (n = 683).
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esh tissues (tumor tissue, at least 50%) and microarray analysis have been reported previously [16,
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Cox proportional hazards regression models were used to assess the prognostic significance of age at diagnosis, primary tumor size, the number of axillary lymph nodes involved, tumor grade, lymphovascular invasion (LVI), ER/PR status, HER2 overexpression, breast cancer subtypes, and the 18-gene score (stratified by either a categorical factor or a continuous variable).
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:28886126", "kind": "science-record", "revision": 7, "content_hash": "sha256:9d8b65283cc04bfd03bffc2c3ce85ae1833948d9df4810dcc468f3fae52b3fdc", "created_at": "2026-11-01T15:40:28Z", "updated_at": "2026-11-01T21:21:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Validation of the 18-gene classifier as a prognostic biomarker of distant metastasis in breast cancer.", "doi": "10.1371/journal.pone.0184372", "pmid": "28886126", "authors": ["Skye Hung-Chun Cheng", "Tzu-Ting Huang", "Yu-Hao Cheng", "Tee Benita Kiat Tan", "Chen-Fang Horng", "Yong Alison Wang", "Nicholas Shannon Brian", "Li-Sun Shih", "Ben-Long Yu"], "journal": "PloS one", "year": 2017, "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. 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