Skip to main content
SpringerLink
Log in

Molecular subtypes of triple-negative breast cancer: understanding of subtype categories and clinical implication

  • Review
  • Published:
Genes & Genomics Aims and scope Submit manuscript

Abstract

Background

Triple-negative breast cancer (TNBC) is a heterogeneous entity that encompasses several subtypes with distinct molecular characteristics. The patients with TNBCs show unpredictable response to the chemotherapy, and further there is the lack of effective agents. Thus, many studies have been underway to discover targeted therapy suitable for patients with specific genetic alterations in each molecular subtypes. TNBCs are classified as four major molecular subtypes according to the gene expression patterns. These are luminal androgen receptor (LAR), mesenchymal-like, immunomodulatory (IM), and basal-like types.

Conclusion

Here, we discuss the unique molecular features of each subtype as well as promising targets for anti-cancer therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Ahn SG, Kim SJ, Kim C, Jeong J (2016) Molecular classification of triple-negative breast cancer. J Breast Cancer 19:223–230

    Article  Google Scholar 

  • Anestis A, Zoi I, Papavassiliou AG, Karamouzis MV (2020) Androgen receptor in breast cancer-clinical and preclinical research insights. Molecules 25:358

    Article  CAS  Google Scholar 

  • Bareche Y, Venet D, Ignatiadis M, Aftimos P, Piccart M, Rothe F, Sotiriou C (2018) Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis. Ann Oncol 29:895–902

    Article  CAS  Google Scholar 

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424

    Article  Google Scholar 

  • Burstein MD, Tsimelzon A, Poage GM, Covington KR, Contreras A, Fuqua SA, Savage MI, Osborne CK, Hilsenbeck SG, Chang JC et al (2015) Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res 21:1688–1698

    Article  CAS  Google Scholar 

  • Dias K, Dvorkin-Gheva A, Hallett RM, Wu Y, Hassell J, Pond GR, Levine M, Whelan T, Bane AL (2017) Claudin-low breast cancer; clinical & pathological characteristics. PLoS One 12:e0168669

    Article  Google Scholar 

  • Farmer P, Bonnefoi H, Becette V, Tubiana-Hulin M, Fumoleau P, Larsimont D, Macgrogan G, Bergh J, Cameron D, Goldstein D et al (2005) Identification of molecular apocrine breast tumours by microarray analysis. Oncogene 24:4660–4671

    Article  CAS  Google Scholar 

  • Gluz O, Liedtke C, Gottschalk N, Pusztai L, Nitz U, Harbeck N (2009) Triple-negative breast cancer–current status and future directions. Ann Oncol 20:1913–1927

    Article  CAS  Google Scholar 

  • Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA, Blackwell K, Rugo H, Nabell L, Forero A et al (2013) Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast cancer. Clin Cancer Res 19:5505–5512

    Article  CAS  Google Scholar 

  • Guiu S, Michiels S, Andre F, Cortes J, Denkert C, Di Leo A, Hennessy BT, Sorlie T, Sotiriou C, Turner N et al (2012) Molecular subclasses of breast cancer: how do we define them? The IMPAKT 2012 Working Group Statement. Ann Oncol 23:2997–3006

    Article  CAS  Google Scholar 

  • Hennessy BT, Gonzalez-Angulo AM, Stemke-Hale K, Gilcrease MZ, Krishnamurthy S, Lee JS, Fridlyand J, Sahin A, Agarwal R, Joy C et al (2009) Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Res 69:4116–4124

    Article  CAS  Google Scholar 

  • Herschkowitz JI, Simin K, Weigman VJ, Mikaelian I, Usary J, Hu Z, Rasmussen KE, Jones LP, Assefnia S, Chandrasekharan S et al (2007) Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors. Genome Biol 8:R76

    Article  Google Scholar 

  • Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, Livasy C, Carey LA, Reynolds E, Dressler L et al (2006) The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genom 7:96

    Article  Google Scholar 

  • Jezequel P, Loussouarn D, Guerin-Charbonnel C, Campion L, Vanier A, Gouraud W, Lasla H, Guette C, Valo I, Verriele V et al (2015) Gene-expression molecular subtyping of triple-negative breast cancer tumours: importance of immune response. Breast Cancer Res 17:43

    Article  Google Scholar 

  • Kim S, Moon BI, Lim W, Park S, Cho MS, Sung SH (2018) Feasibility of classification of triple negative breast cancer by immunohistochemical surrogate markers. Clin Breast Cancer 18:e1123–e1132

    Article  CAS  Google Scholar 

  • Kreike B, van Kouwenhove M, Horlings H, Weigelt B, Peterse H, Bartelink H, van de Vijver MJ (2007) Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res 9:R65

    Article  Google Scholar 

  • Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Investig 121:2750–2767

    Article  CAS  Google Scholar 

  • Liu YR, Jiang YZ, Xu XE, Yu KD, Jin X, Hu X, Zuo WJ, Hao S, Wu J, Liu GY et al (2016) Comprehensive transcriptome analysis identifies novel molecular subtypes and subtype-specific RNAs of triple-negative breast cancer. Breast Cancer Res 18:33

    Article  Google Scholar 

  • Masuda H, Baggerly KA, Wang Y, Zhang Y, Gonzalez-Angulo AM, Meric-Bernstam F, Valero V, Lehmann BD, Pietenpol JA, Hortobagyi GN et al (2013) Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Clin Cancer Res 19:5533–5540

    Article  CAS  Google Scholar 

  • Medina MA, Oza G, Sharma A, Arriaga LG, Hernández Hernández JM, Rotello VM, Ramirez JT (2020) Triple-negative breast cancer: a review of conventional and advanced therapeutic strategies. Int J Environ Res Public Health 17:2078

    Article  CAS  Google Scholar 

  • Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, Davies S, Fauron C, He X, Hu Z et al (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27:1160–1167

    Article  Google Scholar 

  • Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752

    Article  CAS  Google Scholar 

  • Polk A, Svane IM, Andersson M, Nielsen D (2018) Checkpoint inhibitors in breast cancer - current status. Cancer Treat Rev 63:122–134

    Article  CAS  Google Scholar 

  • Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, He X, Perou CM (2010) Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res 12:R68

    Article  Google Scholar 

  • Sabatier R, Finetti P, Guille A, Adelaide J, Chaffanet M, Viens P, Birnbaum D, Bertucci F (2014) Claudin-low breast cancers: clinical, pathological, molecular and prognostic characterization. Mol Cancer 13:228

    Article  Google Scholar 

  • Saha P, Nanda R (2016) Concepts and targets in triple-negative breast cancer: recent results and clinical implications. Ther Adv Med Oncol 8:351–359

    Article  CAS  Google Scholar 

  • Sanga S, Broom BM, Cristini V, Edgerton ME (2009) Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family. BMC Med Genomics 2:59

    Article  Google Scholar 

  • Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874

    Article  Google Scholar 

  • Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100:8418–8423

    Article  CAS  Google Scholar 

  • Sotiriou C, Neo SY, McShane LM, Korn EL, Long PM, Jazaeri A, Martiat P, Fox SB, Harris AL, Liu ET (2003) Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci USA 100:10393–10398

    Article  CAS  Google Scholar 

  • Traina TA, Miller K, Yardley DA, Eakle J, Schwartzberg LS, O’Shaughnessy J, Gradishar W, Schmid P, Winer E, Kelly C et al (2018) Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer. J Clin Oncol 36:884–890

    Article  CAS  Google Scholar 

  • Weigelt B, Mackay A, A’Hern R, Natrajan R, Tan DS, Dowsett M, Ashworth A, Reis-Filho JS (2010) Breast cancer molecular profiling with single sample predictors: a retrospective analysis. Lancet Oncol 11:339–349

    Article  CAS  Google Scholar 

  • Yersal O, Barutca S (2014) Biological subtypes of breast cancer: prognostic and therapeutic implications. World J Clin Oncol 5:412–424

    Article  Google Scholar 

  • Yin L, Duan JJ, Bian XW, Yu SC (2020) Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res 22:61

    Article  Google Scholar 

  • Zhao S, Zuo WJ, Shao ZM, Jiang YZ (2020) Molecular subtypes and precision treatment of triple-negative breast cancer. Ann Transl Med 8:499

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by Basic Science Research Capacity Enhancement Project through Korea Basic Science Institute (National research Facilities and Equipment Center) grant funded by the Ministry of Education (Grant No. 2019R1A6C1010033). The present research was supported by the research fund of Dankook university in 2019 for the University Innovation Support Program.

Author information

Authors and Affiliations

  1. Department of Pathology, School of Medicine, Dankook University, Cheonan, 31116, Republic of Korea

    Yong-Moon Lee & Jai-Hyang Go

  2. Department of Nanobiomedical Science, Dankook University, Cheonan, 31116, Republic of Korea

    Man Hwan Oh

  3. Department of Microbiology, College of Science and Technology, Dankook University, 29 Anseo-dong, Dongnam-gu, Cheonan, 31116, Republic of Korea

    Kyudong Han

  4. Center for Bio-Medical Engineering Core Facility, Dankook University, Cheonan, 31116, Republic of Korea

    Kyudong Han

  5. Department of Pathology, School of Medicine, Chungnam National University, 266 Munwha-Ro, Jung-Gu, Daejeon, 35015, Republic of Korea

    Song-Yi Choi

Authors
  1. Yong-Moon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Man Hwan Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jai-Hyang Go
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kyudong Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Song-Yi Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Kyudong Han or Song-Yi Choi.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, YM., Oh, M.H., Go, JH. et al. Molecular subtypes of triple-negative breast cancer: understanding of subtype categories and clinical implication. Genes Genom 42, 1381–1387 (2020). https://doi.org/10.1007/s13258-020-01014-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13258-020-01014-7

Keywords

Search

Navigation