Review
. 2017 Jun;14(10).
doi: 10.1038/nrclinonc.2017.74.

Clinical utility of gene-expression signatures in early stage breast cancer

Maryann Kwa 1 Andreas Makris 2 Francisco J Esteva 1 
Affiliations
  • PMID: 28561071
  •     103 References
  •     49 citations

Abstract

Breast cancer is a heterogeneous disease, with different subtypes having a distinct biological, molecular, and clinical course. Assessments of standard clinical and pathological features have traditionally been used to determine the use of adjuvant systemic therapy in patients with early stage breast cancer; however, the ability to identify those who will benefit from adjuvant chemotherapy remains a challenge, leading to the overtreatment of some patients. Advances in molecular medicine have substantially improved the accuracy of gene-expression profiling of breast tumours, resulting in improvements in the ability to predict a patient's risk of breast cancer recurrence and likely response to endocrine therapy and/or chemotherapy. These genomic assays, several of which are commercially available, have aided physicians in tailoring treatment decisions for patients at the individual level. Herein, we describe the available data on the clinical validity of the most widely available assays in patients with early stage breast cancer, with a focus on the development, validation, and clinical application of these assays, in addition to the anticipated outcomes of ongoing prospective trials. We also review data from comparative studies of these assays and from cost-effectiveness analyses relating to their clinical use.

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Aneuploidy, TP53 mutation, and amplification of MYC correlate with increased intratumor heterogeneity and poor prognosis of breast cancer patients.
Johanna Oltmann, Kerstin Heselmeyer-Haddad, +15 authors, Thomas Ried.
Genes Chromosomes Cancer, 2017 Nov 29; 57(4). PMID: 29181861    Free PMC article.
Biomarkers in breast cancer: A consensus statement by the Spanish Society of Medical Oncology and the Spanish Society of Pathology.
R Colomer, I Aranda-López, +7 authors, J Palacios-Calvo.
Clin Transl Oncol, 2017 Dec 24; 20(7). PMID: 29273958    Free PMC article.
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The use of automated Ki67 analysis to predict Oncotype DX risk-of-recurrence categories in early-stage breast cancer.
Satbir Singh Thakur, Haocheng Li, +5 authors, Hua Yang.
PLoS One, 2018 Jan 06; 13(1). PMID: 29304138    Free PMC article.
Elevated miR-301a expression indicates a poor prognosis for breast cancer patients.
Jin-Zhou Zheng, Yan-Ni Huang, +5 authors, Zhi-Min Shao.
Sci Rep, 2018 Feb 06; 8(1). PMID: 29396508    Free PMC article.
Neoadjuvant Chemotherapy Exerts Selection Pressure Towards Luminal Phenotype Breast Cancer.
Giulia Galli, Giacomo Bregni, +13 authors, Serena Di Cosimo.
Breast Care (Basel), 2018 Feb 20; 12(6). PMID: 29456471    Free PMC article.
Prognostic role of elevated mir-24-3p in breast cancer and its association with the metastatic process.
Alireza Khodadadi-Jamayran, Betul Akgol-Oksuz, +10 authors, Francisco J Esteva.
Oncotarget, 2018 Mar 22; 9(16). PMID: 29560116    Free PMC article.
Current Status of Neoadjuvant Endocrine Therapy in Early Stage Breast Cancer.
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Curr Treat Options Oncol, 2018 Apr 18; 19(5). PMID: 29663173
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Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer.
Joseph A Sparano, Robert J Gray, +27 authors, George W Sledge.
N Engl J Med, 2018 Jun 05; 379(2). PMID: 29860917    Free PMC article.
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An NFκB-dependent mechanism of tumor cell plasticity and lateral transmission of aggressive features.
Nancy Adriana Espinoza-Sánchez, Jennifer Enciso, Rosana Pelayo, Ezequiel M Fuentes-Pananá.
Oncotarget, 2018 Jun 22; 9(42). PMID: 29928478    Free PMC article.
Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq.
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An Update on Breast Cancer Multigene Prognostic Tests-Emergent Clinical Biomarkers.
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Front Med (Lausanne), 2018 Sep 21; 5. PMID: 30234119    Free PMC article.
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Distribution and Clinical Utility of the 21-gene Recurrence Score in Pure Mucinous Breast Cancer Patients: a case-control study.
Wei Wang, Xiaosong Chen, +12 authors, Kunwei Shen.
J Cancer, 2018 Oct 03; 9(18). PMID: 30271480    Free PMC article.
Evaluating the Prediction of Breast Cancer Survival Using Lymph Node Ratio.
Man Hung, Julie Xu, +4 authors, Maren Wright Voss.
J Breast Cancer, 2018 Oct 03; 21(3). PMID: 30275860    Free PMC article.
GSIAR: gene-subcategory interaction-based improved deep representation learning for breast cancer subcategorical analysis using gene expression, applicable for precision medicine.
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The ever-changing world of gene fusions in cancer: a secondary gene fusion and progression.
Martin P Powers.
Oncogene, 2019 Oct 17; 38(47). PMID: 31616060
Region-specific glucocorticoid receptor promoter methylation has both positive and negative prognostic value in patients with estrogen receptor-positive breast cancer.
Hilary Snider, Brithica Villavarajan, +3 authors, Christopher R Mueller.
Clin Epigenetics, 2019 Nov 05; 11(1). PMID: 31675993    Free PMC article.
Cluster analysis on high dimensional RNA-seq data with applications to cancer research - An evaluation study.
Linda Vidman, David Källberg, Patrik Rydén.
PLoS One, 2019 Dec 06; 14(12). PMID: 31805048    Free PMC article.
Genetic determinants of the molecular portraits of epithelial cancers.
Youli Xia, Cheng Fan, +2 authors, Charles M Perou.
Nat Commun, 2019 Dec 13; 10(1). PMID: 31827079    Free PMC article.
Metastatic Conditioning of Myeloid Cells at a Subcutaneous Synthetic Niche Reflects Disease Progression and Predicts Therapeutic Outcomes.
Robert S Oakes, Grace G Bushnell, +11 authors, Lonnie D Shea.
Cancer Res, 2019 Oct 31; 80(3). PMID: 31662327    Free PMC article.
Value of Molecular Classification for Prognostic Assessment of Adrenocortical Carcinoma.
Guillaume Assié, Anne Jouinot, +32 authors, Jérôme Bertherat.
JAMA Oncol, 2019 Jul 12;. PMID: 31294750    Free PMC article.
Development of an Immune-Related Prognostic Signature in Breast Cancer.
Peiling Xie, Yuying Ma, +3 authors, Huimin Zhang.
Front Genet, 2020 Feb 13; 10. PMID: 32047513    Free PMC article.
Tumour-Infiltrating Immune Cell-Based Subtyping and Signature Gene Analysis in Breast Cancer Based on Gene Expression Profiles.
Jingxin Jiang, Weiwei Pan, +5 authors, Jian Huang.
J Cancer, 2020 Feb 13; 11(6). PMID: 32047563    Free PMC article.
Imaging Phenotypes of Breast Cancer Heterogeneity in Preoperative Breast Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) Scans Predict 10-Year Recurrence.
Rhea D Chitalia, Jennifer Rowland, +7 authors, Despina Kontos.
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Adjuvant chemotherapy could not bring survival benefit to HR-positive, HER2-negative, pT1b-c/N0-1/M0 invasive lobular carcinoma of the breast: a propensity score matching study based on SEER database.
Guangfu Hu, Guangxia Hu, +8 authors, Cheng Xu.
BMC Cancer, 2020 Feb 23; 20(1). PMID: 32085753    Free PMC article.
Cross comparison and prognostic assessment of breast cancer multigene signatures in a large population-based contemporary clinical series.
Johan Vallon-Christersson, Jari Häkkinen, +12 authors, Johan Staaf.
Sci Rep, 2019 Aug 23; 9(1). PMID: 31434940    Free PMC article.
Proteomics and phosphoproteomics in precision medicine: applications and challenges.
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Neoadjuvant Management of Early Breast Cancer: A Clinical and Investigational Position Statement.
Ramon Colomer, Cristina Saura, +7 authors, Ana Lluch.
Oncologist, 2019 Feb 03; 24(5). PMID: 30710068    Free PMC article.
Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments.
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Aim for Clinical Utility, Not Just Predictive Accuracy.
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Epidemiology, 2020 Feb 25; 31(3). PMID: 32091429    Free PMC article.
Programmed death-ligand 1 gene expression is a prognostic marker in early breast cancer and provides additional prognostic value to 21-gene and 70-gene signatures in estrogen receptor-positive disease.
Ioannis Zerdes, Emmanouil G Sifakis, +6 authors, Theodoros Foukakis.
Mol Oncol, 2020 Mar 03; 14(5). PMID: 32115850    Free PMC article.
RNA-seq analysis identified hormone-related genes associated with prognosis of triple negative breast cancer.
Fei Chen, Yuancheng Li, +10 authors, Hongbing Shen.
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Cancer genomics predicts disease relapse and therapeutic response to neoadjuvant chemotherapy of hormone sensitive breast cancers.
Jieqiang Zhu, Levan Muskhelishvili, +2 authors, Minjun Chen.
Sci Rep, 2020 May 20; 10(1). PMID: 32424219    Free PMC article.
Do 21-Gene Recurrence Score Influence Chemotherapy Decisions in T1bN0 Breast Cancer Patients?
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Front Oncol, 2020 Jun 02; 10. PMID: 32477946    Free PMC article.
Analysis of Immune Checkpoint Drug Targets and Tumor Proteotypes in Non-Small Cell Lung Cancer.
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Sci Rep, 2020 Jun 20; 10(1). PMID: 32555523    Free PMC article.
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Oncol Lett, 2020 Jul 30; 20(2). PMID: 32724396    Free PMC article.
Expression Patterns of Immune Genes Reveal Heterogeneous Subtypes of High-Risk Neuroblastoma.
Zhenqiu Liu, Christa N Grant, +3 authors, Hong-Gang Wang.
Cancers (Basel), 2020 Jul 08; 12(7). PMID: 32629858    Free PMC article.
The 21-Gene Recurrence Score Assay and Prediction of Chemotherapy Benefit: A Propensity Score-Matched Analysis of the SEER Database.
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Cancers (Basel), 2020 Jul 12; 12(7). PMID: 32650374    Free PMC article.
Precision medicine for locally advanced breast cancer: frontiers and challenges in Latin America.
Joseph A Pinto, César H Saravia, +10 authors, Henry L Gómez.
Ecancermedicalscience, 2019 Feb 23; 13. PMID: 30792813    Free PMC article.
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The evolving role of molecular profiling in prostate cancer: basal and luminal subtyping transcends tissue of origin.
Omar Y Mian, Rahul D Tendulkar, Mohamed E Abazeed.
Transl Cancer Res, 2017 Dec 01; 6(Suppl 9). PMID: 30873354    Free PMC article.
A Pathology-Based Combined Model to Identify PAM50 Non-luminal Intrinsic Disease in Hormone Receptor-Positive HER2-Negative Breast Cancer.
Tomás Pascual, Miguel Martin, +21 authors, Aleix Prat.
Front Oncol, 2019 May 21; 9. PMID: 31106144    Free PMC article.
Tumor derived EDIL3 modulates the expansion and osteoclastogenesis of myeloid derived suppressor cells in murine breast cancer model.
Zhang Kun, Gao Xin, +5 authors, Xiao Jianru.
J Bone Oncol, 2019 May 22; 16. PMID: 31110935    Free PMC article.
Prognostic impact of interleukin-6 and C-reactive protein on patients with breast cancer.
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Should a Multigene Signature be Used in all Luminal Early Breast Cancers.
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Front Oncol, 2019 Jun 20; 9. PMID: 31214499    Free PMC article.
LncRNA LINC00668 promotes the progression of breast cancer by inhibiting apoptosis and accelerating cell cycle.
Xia Qiu, Jiangnan Dong, +2 authors, Xiaoyan Cai.
Onco Targets Ther, 2019 Aug 03; 12. PMID: 31371999    Free PMC article.
Genomic Signatures in Luminal Breast Cancer.
Julian Puppe, Tabea Seifert, +3 authors, Wolfram Malter.
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MKL1 Mediates TGF-β Induced RhoJ Transcription to Promote Breast Cancer Cell Migration and Invasion.
Baoyu Chen, Yibiao Yuan, +4 authors, Yong Xu.
Front Cell Dev Biol, 2020 Sep 29; 8. PMID: 32984327    Free PMC article.
Radiogenomic signatures reveal multiscale intratumour heterogeneity associated with biological functions and survival in breast cancer.
Ming Fan, Pingping Xia, +2 authors, Lihua Li.
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Racial and ethnic disparities in 21-gene recurrence scores, chemotherapy, and survival among women with hormone receptor-positive, node-negative breast cancer.
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EXCLI J, 2020 Nov 17; 19. PMID: 33192212    Free PMC article.