Breast Cancer

, Volume 25, Issue 4, pp 489–496 | Cite as

Effect of the normal mammary differentiation regulator ELF5 upon clinical outcomes of triple negative breast cancers patients

  • Fumiya Omata
  • Keely May McNamara
  • Koyu Suzuki
  • Eriko Abe
  • Hisashi Hirakawa
  • Takanori Ishida
  • Noriaki Ohuchi
  • Hironobu Sasano
Rapid Communication



Elf5 is a transcription factor previously shown to be involved in regulating cell differentiation in both normal and pathological breast tissues. Pertinently, Elf5 was reported to interact with the FOXA1 transcription factor, a pivotal regulatory factor in a subset of AR overexpressing triple negative cancer (TNBC) cases.


We examined the correlation among AR, FOXA1, and Elf5 expression in a series of TNBC cases. The cases were retrieved from surgical pathological files of Tohoku University Hospital Japan and consisted of 60 cases operated between the year 1999 and 2007. An additional cohort cases of 51 TNBC ductal carcinoma in situ was used to compare invasive and non-invasive TNBC.


In our cohort, 47% of all carcinomas were positive for Elf5, with a significantly higher proportion of Elf5 positive cases occurring in the younger age groups (p = 0.0061). Elf5 immunoreactivity was not associated with any other clinicopathological factors examined in this study. However, Elf5 expression was associated with decreased overall and disease-free survival of the patients (Peto–Peto modification of Gehan–Wilcoxon test, OS p = 0.132, DFS p = 0.1 (LI cutoff 10%); OS p = 0.038, DFS p = 0.021 (LI cutoff 50%)). Of particular interest, its effects on survival were more pronounced in the EGFR−/CK5/6− (non-basal surrogate) than the EGFR+ and/or CK5/6+ (basal-surrogate) subtype of TNBC.


Elf5 is present in TNBC and its status was significantly correlated with overall survival of the patients. Further studies examining possible interactions between Elf5 and other factors in TNBC could contribute to disentangling TNBC biology.


Elf5 Breast cancer TNBC Steroids Basal EGFR Differentiation Androgens Estrogens Survival outcomes 



We would like to thank staff and colleagues at the Department of Anatomical Pathology for their guidance and support during manuscript preparation. We would also like to thank Dr Vladimiros Thoma for his careful proofreading of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors have no relevant conflicts of interest.

Supplementary material

12282_2018_842_MOESM1_ESM.pptx (102 kb)
Supplementary material 1 (PPTX 101 kb)


  1. 1.
    Zhou J, et al. A novel transcription factor, ELF5, belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13–15, a region subject to LOH and rearrangement in human carcinoma cell lines. Oncogene. 1998;17(21):2719–32.CrossRefPubMedGoogle Scholar
  2. 2.
    Choi YS, et al. Elf5 conditional knockout mice reveal its role as a master regulator in mammary alveolar development: failure of Stat5 activation and functional differentiation in the absence of Elf5. Dev Biol. 2009;329(2):227–41.CrossRefPubMedGoogle Scholar
  3. 3.
    Oakes SR, et al. The Ets transcription factor Elf5 specifies mammary alveolar cell fate. Genes Dev. 2008;22(5):581–6.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Lee HJ, et al. Progesterone drives mammary secretory differentiation via RankL-mediated induction of Elf5 in luminal progenitor cells. Development. 2013;140(7):1397–401.CrossRefPubMedGoogle Scholar
  5. 5.
    Chakrabarti R, et al. Elf5 regulates mammary gland stem/progenitor cell fate by influencing notch signaling. Stem Cells. 2012;30(7):1496–508.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Harris J, et al. Socs2 and elf5 mediate prolactin-induced mammary gland development. Mol Endocrinol. 2006;20(5):1177–87.CrossRefPubMedGoogle Scholar
  7. 7.
    Kalyuga M, et al. ELF5 suppresses estrogen sensitivity and underpins the acquisition of antiestrogen resistance in luminal breast cancer. PLoS Biol. 2012;10(12):e1001461.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    McNamara KM, et al. Androgen receptor and enzymes in lymph node metastasis and cancer reoccurrence in triple-negative breast cancer. Int J Biol Markers. 2015;30(2):184–9.CrossRefGoogle Scholar
  9. 9.
    McNamara KM, et al. Androgenic pathways in the progression of triple-negative breast carcinoma: a comparison between aggressive and non-aggressive subtypes. Breast Cancer Res Treat. 2014;145(2):281–93.CrossRefPubMedGoogle Scholar
  10. 10.
    McNamara K, et al. Androgenic pathway in triple negative invasive ductal tumours: its correlation with tumour cell proliferation. Cancer Sci. 2013;104(5):639–46.CrossRefPubMedGoogle Scholar
  11. 11.
    Robinson JL, et al. Androgen receptor driven transcription in molecular apocrine breast cancer is mediated by FoxA1. EMBO J. 2011;30(15):3019–27.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    McNamara KM, et al. The presence and impact of estrogen metabolism on the biology of triple-negative breast cancer. Breast Cancer Res Treat. 2017;161(2):213–27.CrossRefPubMedGoogle Scholar
  13. 13.
    Miyashita M, et al. Histopathological subclassification of triple negative breast cancer using prognostic scoring system: five variables as candidates. Virchows Arch. 2011;458(1):65–72.CrossRefPubMedGoogle Scholar
  14. 14.
    Reyes ME, et al. Poor prognosis of patients with triple-negative breast cancer can be stratified by RANK and RANKL dual expression. Breast Cancer Res Treat. 2017;164(1):57–67.CrossRefPubMedGoogle Scholar
  15. 15.
    Rangel MC, et al. Developmental signaling pathways regulating mammary stem cells and contributing to the etiology of triple-negative breast cancer. Breast Cancer Res Treat. 2016;156(2):211–26.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Kim S, et al. Impact of suppression of tumorigenicity 14 (ST14)/serine protease 14 (Prss14) expression analysis on the prognosis and management of estrogen receptor negative breast cancer. Oncotarget. 2016;7(23):34643–63.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Piggin CL, et al. ELF5 isoform expression is tissue-specific and significantly altered in cancer. Breast Cancer Res. 2016;18(1):4.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Tarulli GA, et al. Bringing androgens up a NOTCH in breast cancer. Endocr Relat Cancer. 2014;21(4):T183–202.CrossRefPubMedGoogle Scholar
  19. 19.
    Lehmann BD, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Investig. 2011;121(7):2750–67.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Farmer P, et al. Identification of molecular apocrine breast tumours by microarray analysis. Oncogene. 2005;24(29):4660–71.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Breast Cancer Society 2018

Authors and Affiliations

  • Fumiya Omata
    • 1
  • Keely May McNamara
    • 1
  • Koyu Suzuki
    • 2
  • Eriko Abe
    • 2
  • Hisashi Hirakawa
    • 3
  • Takanori Ishida
    • 4
  • Noriaki Ohuchi
    • 4
  • Hironobu Sasano
    • 1
  1. 1.Department of Anatomical PathologyTohoku University School of MedicineSendaiJapan
  2. 2.Department of PathologySt Lukes HospitalTokyoJapan
  3. 3.Department of PathologyKosai HospitalSendaiJapan
  4. 4.Department of SurgeryTohoku University School of MedicineSendaiJapan

Personalised recommendations