Journal Article
. 2016 Apr;5().
doi: 10.1016/j.ebiom.2016.02.022.

An Eighteen-Gene Classifier Predicts Locoregional Recurrence in Post-Mastectomy Breast Cancer Patients

Skye H Cheng 1 Chen-Fang Horng 1 Tzu-Ting Huang 1 Erich S Huang 2 Mei-Hua Tsou 1 Li-Sun Shi 3 Ben-Long Yu 4 Chii-Ming Chen 1 Andrew T Huang 5 
Affiliations
  • PMID: 27077114
  •     39 References
  •     8 citations

Abstract

We previously identified 34 genes of interest (GOI) in 2006 to aid the oncologists to determine whether post-mastectomy radiotherapy (PMRT) is indicated for certain patients with breast cancer. At this time, an independent cohort of 135 patients having DNA microarray study available from the primary tumor tissue samples was chosen. Inclusion criteria were 1) mastectomy as the first treatment, 2) pathology stages I-III, 3) any locoregional recurrence (LRR) and 4) no PMRT. After inter-platform data integration of Affymetrix U95 and U133 Plus 2.0 arrays and quantile normalization, in this paper we used 18 of 34 GOI to divide the mastectomy patients into high and low risk groups. The 5-year rate of freedom from LRR in the high-risk group was 30%. In contrast, in the low-risk group it was 99% (p < 0.0001). Multivariate analysis revealed that the 18-gene classifier independently predicts rates of LRR regardless of nodal status or cancer subtype.

Keywords: Breast cancer; Breast-conserving surgery; Gene-expression profiles; Locoregional recurrence; Mastectomy; Prediction; Radiotherapy.

A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL.
M P Kamps, C Murre, X H Sun, D Baltimore.
Cell, 1990 Feb 23; 60(4). PMID: 1967983
Highly Cited.
Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial.
Joseph Ragaz, Ivo A Olivotto, +11 authors, Mohamed Manji.
J Natl Cancer Inst, 2005 Jan 20; 97(2). PMID: 15657341
Highly Cited.
Meta-analysis of microarray studies reveals a novel hematopoietic progenitor cell signature and demonstrates feasibility of inter-platform data integration.
Davendra Sohal, Andrew Yeatts, +10 authors, Amit Verma.
PLoS One, 2008 Aug 14; 3(8). PMID: 18698424    Free PMC article.
Development and validation of a gene profile predicting benefit of postmastectomy radiotherapy in patients with high-risk breast cancer: a study of gene expression in the DBCG82bc cohort.
Trine Tramm, Hayat Mohammed, +6 authors, Jens Overgaard.
Clin Cancer Res, 2014 Aug 26; 20(20). PMID: 25149560
Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials.
M Clarke, R Collins, +14 authors, Early Breast Cancer Trialists' Collaborative Group (EBCTCG).
Lancet, 2005 Dec 20; 366(9503). PMID: 16360786
Highly Cited. Review.
Prognostic index score and clinical prediction model of local regional recurrence after mastectomy in breast cancer patients.
Skye Hongiun Cheng, Cheng-Fang Horng, +8 authors, Leonard R Prosnitz.
Int J Radiat Oncol Biol Phys, 2006 Feb 14; 64(5). PMID: 16472935
Comparison of PAM50 risk of recurrence score with oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy.
Mitch Dowsett, Ivana Sestak, +7 authors, Jack Cuzick.
J Clin Oncol, 2013 Jul 03; 31(22). PMID: 23816962
Highly Cited.
Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer.
Philip M Poortmans, Sandra Collette, +22 authors, EORTC Radiation Oncology and Breast Cancer Groups.
N Engl J Med, 2015 Jul 23; 373(4). PMID: 26200978
Highly Cited.
Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte chemotactic peptide receptors.
H Nomura, B W Nielsen, K Matsushima.
Int Immunol, 1993 Oct 01; 5(10). PMID: 7505609
Overexpression of P70 S6 kinase protein is associated with increased risk of locoregional recurrence in node-negative premenopausal early breast cancer patients.
J A van der Hage, L J C M van den Broek, +5 authors, M J van de Vijver.
Br J Cancer, 2004 Apr 15; 90(8). PMID: 15083183    Free PMC article.
The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Initiative: methods of the EGAPP Working Group.
Steven M Teutsch, Linda A Bradley, +7 authors, EGAPP Working Group.
Genet Med, 2008 Sep 25; 11(1). PMID: 18813139    Free PMC article.
Highly Cited.
Gene expression profiling predicts clinical outcome of breast cancer.
Laura J van 't Veer, Hongyue Dai, +13 authors, Stephen H Friend.
Nature, 2002 Feb 02; 415(6871). PMID: 11823860
Highly Cited.
Classification of human breast cancer using gene expression profiling as a component of the survival predictor algorithm.
Gennadi V Glinsky, Takuya Higashiyama, Anna B Glinskii.
Clin Cancer Res, 2004 Apr 10; 10(7). PMID: 15073102
The Bloom's syndrome gene product is homologous to RecQ helicases.
N A Ellis, J Groden, +5 authors, J German.
Cell, 1995 Nov 17; 83(4). PMID: 7585968
Highly Cited.
A human suppressor of c-Jun N-terminal kinase 1 activation by tumor necrosis factor alpha.
D Y Jin, H Teramoto, +3 authors, K T Jeang.
J Biol Chem, 1997 Nov 05; 272(41). PMID: 9325311
Temporal Trends in Postmastectomy Radiation Therapy and Breast Reconstruction Associated With Changes in National Comprehensive Cancer Network Guidelines.
Lane L Frasier, Sara Holden, +5 authors, Heather B Neuman.
JAMA Oncol, 2015 Nov 06; 2(1). PMID: 26539936    Free PMC article.
yes-related protooncogene, syn, belongs to the protein-tyrosine kinase family.
K Semba, M Nishizawa, +6 authors, K Toyoshima.
Proc Natl Acad Sci U S A, 1986 Aug 01; 83(15). PMID: 3526330    Free PMC article.
Highly Cited.
Concordance among gene-expression-based predictors for breast cancer.
Cheng Fan, Daniel S Oh, +5 authors, Charles M Perou.
N Engl J Med, 2006 Aug 11; 355(6). PMID: 16899776
Highly Cited.
Racial and ethnic differences in breast cancer survival: how much is explained by screening, tumor severity, biology, treatment, comorbidities, and demographics?
Elana Curtis, Chris Quale, David Haggstrom, Rebecca Smith-Bindman.
Cancer, 2007 Nov 28; 112(1). PMID: 18040998    Free PMC article.
Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization.
Kuo-Jang Kao, Kai-Ming Chang, Hui-Chi Hsu, Andrew T Huang.
BMC Cancer, 2011 Apr 20; 11. PMID: 21501481    Free PMC article.
Highly Cited.
Regional Nodal Irradiation in Early-Stage Breast Cancer.
Timothy J Whelan, Ivo A Olivotto, +21 authors, MA.20 Study Investigators.
N Engl J Med, 2015 Jul 23; 373(4). PMID: 26200977    Free PMC article.
Highly Cited.
Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.
Soonmyung Paik, Gong Tang, +11 authors, Norman Wolmark.
J Clin Oncol, 2006 May 25; 24(23). PMID: 16720680
Highly Cited.
Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials.
Alphonse Taghian, Jong-Hyeon Jeong, +4 authors, Norman Wolmark.
J Clin Oncol, 2004 Sep 29; 22(21). PMID: 15452182
Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology.
A Recht, S B Edge, +14 authors, American Society of Clinical Oncology.
J Clin Oncol, 2001 Mar 07; 19(5). PMID: 11230499
Highly Cited.
A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.
Soonmyung Paik, Steven Shak, +12 authors, Norman Wolmark.
N Engl J Med, 2004 Dec 14; 351(27). PMID: 15591335
Highly Cited.
A decision impact, decision conflict and economic assessment of routine Oncotype DX testing of 146 women with node-negative or pNImi, ER-positive breast cancer in the U.K.
S Holt, G Bertelli, +12 authors, C J Phillips.
Br J Cancer, 2013 May 23; 108(11). PMID: 23695023    Free PMC article.
Genetic tests and genomic biomarkers: regulation, qualification and validation.
Giuseppe Novelli, Cinzia Ciccacci, +2 authors, Eric Abadie.
Clin Cases Miner Bone Metab, 2008 May 01; 5(2). PMID: 22460999    Free PMC article.
A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast.
Lawrence J Solin, Robert Gray, +13 authors, Sunil Badve.
J Natl Cancer Inst, 2013 May 04; 105(10). PMID: 23641039    Free PMC article.
Highly Cited.
Isolation of a human cyclin cDNA: evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2.
J Pines, T Hunter.
Cell, 1989 Sep 08; 58(5). PMID: 2570636
Highly Cited.
[Cost-effectiveness of a chemotherapy predictive test].
Anne-Lise Vataire, Enora Laas, +3 authors, Elisabeth Chéreau.
Bull Cancer, 2012 Oct 09; 99(10). PMID: 23041366
Prognostic value of p53 for local failure in mastectomy-treated breast cancer patients.
R C Zellars, S G Hilsenbeck, +4 authors, R M Elledge.
J Clin Oncol, 2000 Apr 28; 18(9). PMID: 10784631
A gene-expression signature as a predictor of survival in breast cancer.
Marc J van de Vijver, Yudong D He, +18 authors, René Bernards.
N Engl J Med, 2002 Dec 20; 347(25). PMID: 12490681
Highly Cited.
Radiotherapy for early breast cancer.
Early Breast Cancer Trialists' Collaborative Group.
Cochrane Database Syst Rev, 2002 Jun 22; (2). PMID: 12076497
Systematic Review.
Gene expression profiling for prediction of clinical characteristics of breast cancer.
Erich Huang, Mike West, Joseph R Nevins.
Recent Prog Horm Res, 2003 Jun 11; 58. PMID: 12795414
Review.
Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials.
EBCTCG (Early Breast Cancer Trialists' Collaborative Group), P McGale, +11 authors, S Darby.
Lancet, 2014 Mar 25; 383(9935). PMID: 24656685    Free PMC article.
Highly Cited.
Genomic prediction of locoregional recurrence after mastectomy in breast cancer.
Skye H Cheng, Cheng-Fang Horng, +10 authors, Andrew T Huang.
J Clin Oncol, 2006 Sep 30; 24(28). PMID: 17008701
Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications.
T Sørlie, C M Perou, +14 authors, A L Børresen-Dale.
Proc Natl Acad Sci U S A, 2001 Sep 13; 98(19). PMID: 11553815    Free PMC article.
Highly Cited.
The molecular basis for the absence of N-glycolylneuraminic acid in humans.
A Irie, S Koyama, +2 authors, A Suzuki.
J Biol Chem, 1998 Jun 23; 273(25). PMID: 9624188
Highly Cited.
Economic evaluation of the 21-gene signature (Oncotype DX) in lymph node-negative/positive, hormone receptor-positive early-stage breast cancer based on Japanese validation study (JBCRG-TR03).
Masahide Kondo, Shu-Ling Hoshi, +2 authors, Masakazu Toi.
Breast Cancer Res Treat, 2010 Nov 18; 127(3). PMID: 21082239
Validation of the 18-gene classifier as a prognostic biomarker of distant metastasis in breast cancer.
Skye Hung-Chun Cheng, Tzu-Ting Huang, +6 authors, Ben-Long Yu.
PLoS One, 2017 Sep 09; 12(9). PMID: 28886126    Free PMC article.
Gene expression profiling in prognosis of distant recurrence in HR-positive and HER2-negative breast cancer patients.
Tzu-Ting Huang, Nicolas Pennarun, +3 authors, Skye Hung-Chun Cheng.
Oncotarget, 2018 May 26; 9(33). PMID: 29796180    Free PMC article.
A preliminary report of head-to-head comparison of 18-gene-based clinical-genomic model and oncotype DX 21-gene assay for predicting recurrence of early-stage breast cancer.
Po-Sheng Yang, Yi-Hsuan Lee, +9 authors, Chiun-Sheng Huang.
Jpn J Clin Oncol, 2019 Jul 10; 49(11). PMID: 31287883    Free PMC article.
A new clinical-genomic model to predict 10-year recurrence risk in primary operable breast cancer patients.
Tzu-Ting Huang, Lei Lei, +3 authors, Skye Hung-Chun Cheng.
Sci Rep, 2020 Mar 19; 10(1). PMID: 32184406    Free PMC article.
Comparison of long-term results between radiotherapy after breast-conserving surgery and postmastectomy radiotherapy in stage T1-2N1M0 breast cancer.
Xiao-Wen Lan, Ge Wen, +5 authors, Xiao-Bo Huang.
Cancer Manag Res, 2019 Aug 03; 11. PMID: 31372049    Free PMC article.
An Emerging Role for Radiation Oncology in Precision Oncology.
Sharad Goyal, Bruce G Haffty.
EBioMedicine, 2016 Apr 15; 5. PMID: 27077098    Free PMC article.
An 8‑gene signature predicts the prognosis of cervical cancer following radiotherapy.
Fei Xie, Dan Dong, +7 authors, Guixiang Tai.
Mol Med Rep, 2019 Aug 23; 20(4). PMID: 31432147    Free PMC article.
A 23-gene prognostic classifier for prediction of recurrence and survival for Asian breast cancer patients.
Ting-Hao Chen, Jian-Ying Chiu, Kuan-Hui Shih.
Biosci Rep, 2020 Nov 24; 40(12). PMID: 33226082    Free PMC article.