Article Text

Download PDFPDF
Characteristics, behaviour and role of biomarkers in metastatic triple-negative breast cancer
  1. Yutaro Goto1,2,
  2. Aye Aye Thike2,3,
  3. Clara Chong Hui Ong2,
  4. Johnathan Xiande Lim2,
  5. Nur Diyana Md Nasir2,
  6. Huihua Li4,5,
  7. Valerie Cui Yun Koh2,
  8. Xiao-Yang Chen2,6,
  9. Joe Poh Sheng Yeong2,7,
  10. Hironobu Sasano1,8,
  11. Puay Hoon Tan3,6,9
  1. 1 Anatomic Pathology, Tohoku University School of Medicine, Sendai, Miyagi, Japan
  2. 2 Anatomical Pathology, Singapore General Hospital, Singapore, Singapore
  3. 3 Duke-NUS Medical School, Singapore, Singapore
  4. 4 Health Services Research Unit, Singapore General Hospital, Singapore, Singapore
  5. 5 Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore, Singapore
  6. 6 Anatomy, National University Singapore Yong Loo Lin School of Medicine, Singapore, Singapore
  7. 7 Integrative Biology for Theranostics, Institute of Molecular and Cell Biology, Singapore, Singapore
  8. 8 Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan
  9. 9 Pathology, Singapore General Hospital, Singapore, Singapore
  1. Correspondence to Professor Puay Hoon Tan, Pathology, Singapore General Hospital, Singapore, Singapore; tan.puay.hoon{at}


Aims Characterising the factors responsible for metastatic triple-negative breast cancer (TNBC) is of significant importance, considering its high mortality rate and scant data. In this study, we evaluated the characteristics, clinical behaviour and role of biomarkers (androgen receptor (AR), oestrogen receptor beta (ERβ) and p53) in metastatic TNBC.

Methods Immunohistochemistry was performed for AR, ERβ and p53 on 125 primary TNBCs with known metastasis and correlated with clinicopathological parameters and outcome. AR and p53 mRNA profiling was also carried out on 34 tumours from the same series and correlated with outcomes.

Results In this cohort, grade 3 and pT2 tumours predominated. The most common site for metastasis was the lung and pleura (41, 32.8%), and 15 (12.0%) cases demonstrated metastasis in multiple sites. Among these, 92% of tumours metastasised without preceding local recurrences. Five- and ten-year overall survival (OS) rates were 27% and 7.2%, while 5- and 10- year survival rates after metastasis were 9.6% and 3.2% respectively. AR, ERβ and p53 protein expressions were observed in 16%, 96.8% and 58.1% of tumours, respectively. A combinational phenotype of AR-ERβ+p53+ tumours was associated with poorer OS (HR 1.543, 95%CI 1.030 to 2.310, p=0.035). Higher AR mRNA levels were significantly associated with favourable OS (p=0.015) and survival after metastasis (p=0.027).

Conclusions Metastatic TNBC harboured aggressive behaviour and displayed predominantly visceral metastasis with most metastatic events occurring without intervening local recurrences. A combinational phenotype of AR-ERβ+p53+ was significantly associated with poorer OS.

  • Metastatic triple negative breast cancer
  • protein and mRNA expression
  • outcomes
  • androgen receptor
  • estrogen receptor
  • p53

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Handling editor Cheok Soon Lee.

  • Contributors PHT conceived and designed the study. YG and AAT wrote the manuscript. CCHO, JXL and NDMN performed the TMA construction, cutting and staining of tissue sections. YG and AAT quantified the immunoscoring. AAT, HL and VCYK performed the data analyses. AAT, VCYK, X-YC, JPSY, HS and PHT revised the manuscript critically for content.

  • Funding This study was funded by the National Medical Research Council, Singapore (SMPO201302).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval All procedures performed in this study were in accordance with the ethical standards of the SingHealth Centralised Institutional Review Board (CIRB) (Ref: 2013/664/F). The SingHealth CIRB operates in accordance with the ICH Guideline for Good Clinical Practice and with the applicable regulatory requirements. This article does not contain any studies with animals performed by any of the authors. A waiver for informed consent was approved by the SingHealth CIRB.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.