Skip to main content

Advertisement

Log in

Coexistent Loss of the Expressions of BRCA1 and p53 Predicts Poor Prognosis in Triple-Negative Breast Cancer

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

To investigate the prognostic significance of altered breast cancer susceptibility gene 1 (BRCA1) and p53 expression in triple-negative breast cancer (TNBC).

Methods

Immunohistochemical expression of BRCA1 and p53 was examined in the tumor tissues of 465 TNBC cases and relations were sought with clinicopathological features and patient survival.

Results

Loss of BRCA1 expression was found in 29.5% (137/465) of TNBCs. Positive expression of p53 was observed in 49.9% (232/465). Patients with loss of BRCA1 expression had a tendency to have higher rate of lymph node metastasis (p = 0.075). An association between p53 expression and high histological grade was observed (p = 0.039). TNBC patients with loss of BRCA1 expression had a tendency to have poorer overall survival (OS) than those positive for BRCA1 (p = 0.09). TNBC patients with positive p53 expression showed better OS than those with p53 negativity (p = 0.001). In terms of combined expression patterns, significantly poorer overall survival (OS) was observed for BRCA1-negative/p53-negative TNBCs and best OS for BRCA1-positive/p53-positive TNBCs (p = 0.005).

Conclusions

Combined expression patterns of BRCA1 and p53 could serve as useful prognostic markers in TNBC.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13:4429-34.

    Article  PubMed  Google Scholar 

  2. Tischkowitz M, Brunet JS, Begin LR, et al. Use of immunohistochemical markers can refine prognosis in triple negative breast cancer. BMC Cancer. 2007;7:134.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Kim J, Hwang T, Kang S, Lee S, Bae Y. Prognostic Significance of Basal Markers in Triple-negative Breast Cancers. J Breast Cancer. 2009;12:4-13.

    Article  Google Scholar 

  4. Choi JE, Kang SH, Lee SJ, Bae YK. Prognostic significance of Bcl-2 expression in non-basal triple-negative breast cancer patients treated with anthracycline-based chemotherapy. Tumour Biol. 2014;35:12255-63.

    Article  CAS  PubMed  Google Scholar 

  5. Choi JE, Kang SH, Lee SJ, Bae YK. Androgen receptor expression predicts decreased survival in early stage triple-negative breast cancer. Ann Surg Oncol. 2015;22:82-9.

    Article  PubMed  Google Scholar 

  6. Somasundaram K. Breast cancer gene 1 (BRCA1): role in cell cycle regulation and DNA repair–perhaps through transcription. J Cell Biochem. 2003;88:1084-91.

    Article  CAS  PubMed  Google Scholar 

  7. Ouchi T, Monteiro AN, August A, Aaronson SA, Hanafusa H. BRCA1 regulates p53-dependent gene expression. Proc Natl Acad Sci U S A. 1998;95:2302-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zhang H, Somasundaram K, Peng Y, et al. BRCA1 physically associates with p53 and stimulates its transcriptional activity. Oncogene. 1998;16:1713-21.

    Article  CAS  PubMed  Google Scholar 

  9. Miki Y, Swensen J, Shattuck-Eidens D, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994;266:66-71.

    Article  CAS  PubMed  Google Scholar 

  10. Yoshikawa K, Honda K, Inamoto T, et al. Reduction of BRCA1 protein expression in Japanese sporadic breast carcinomas and its frequent loss in BRCA1-associated cases. Clin Cancer Res. 1999;5:1249-61.

    CAS  PubMed  Google Scholar 

  11. Yang Q, Sakurai T, Mori I, et al. Prognostic significance of BRCA1 expression in Japanese sporadic breast carcinomas. Cancer. 2001;92:54-60.

    Article  CAS  PubMed  Google Scholar 

  12. Kurebayashi J, Yamamoto Y, Kurosumi M, Okubo S, Nomura T, Tanaka K, Sonoo H. Loss of BRCA1 expression may predict shorter time-to-progression in metastatic breast cancer patients treated with taxanes. Anticancer Res. 2006;26:695-701.

    CAS  PubMed  Google Scholar 

  13. Rakha EA, El-Sheikh SE, Kandil MA, El-Sayed ME, Green AR, Ellis IO. Expression of BRCA1 protein in breast cancer and its prognostic significance. Hum Pathol. 2008;39:857-65.

    Article  CAS  PubMed  Google Scholar 

  14. Zhu X, Shan L, Wang F, et al. Hypermethylation of BRCA1 gene: implication for prognostic biomarker and therapeutic target in sporadic primary triple-negative breast cancer. Breast Cancer Res Treat. 2015;150:479-86.

    Article  CAS  PubMed  Google Scholar 

  15. Yamashita N, Tokunaga E, Kitao H, et al. Epigenetic Inactivation of BRCA1 Through Promoter Hypermethylation and Its Clinical Importance in Triple-Negative Breast Cancer. Clin Breast Cancer. 2015;15:498-504.

    Article  CAS  PubMed  Google Scholar 

  16. Okada S, Tokunaga E, Kitao H, et al. Loss of heterozygosity at BRCA1 locus is significantly associated with aggressiveness and poor prognosis in breast cancer. Ann Surg Oncol. 2012;19:1499-507.

    Article  PubMed  Google Scholar 

  17. Lacroix M, Toillon RA, Leclercq G. P53 and Breast Cancer, an Update. Endocr Relat Cancer. 2006;13:293-325.

    Article  CAS  PubMed  Google Scholar 

  18. Borresen-Dale AL. TP53 and breast cancer. Hum Mutat. 2003;21:292-300.

    Article  CAS  PubMed  Google Scholar 

  19. Petitjean A, Mathe E, Kato S, Ishioka C, Tavtigian SV, Hainaut P, Olivier M. Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat. 2007;28:622-9.

    Article  CAS  PubMed  Google Scholar 

  20. Dumay A, Feugeas JP, Wittmer E, et al. Distinct tumor protein p53 mutants in breast cancer subgroups. Int J Cancer. 2013;132:1227-31.

    Article  CAS  PubMed  Google Scholar 

  21. Bertheau P, Lehmann-Che J, Varna M, et al. P53 in Breast Cancer Subtypes and New Insights into Response to Chemotherapy. Breast. 2013;22 Suppl 2:S27-9.

    Article  PubMed  Google Scholar 

  22. Pharoah PD, Day NE, Caldas C. Somatic mutations in the p53 gene and prognosis in breast cancer: a meta-analysis. Br J Cancer. 1999;80:1968-73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Biganzoli E, Coradini D, Ambrogi F, et al. P53 Status Identifies Two Subgroups of Triple-Negative Breast Cancers with Distinct Biological Features. Jpn J Clin Oncol. 2011;41:172-9.

    Article  PubMed  Google Scholar 

  24. Coates AS, Millar EK, O’Toole SA, et al. Prognostic interaction between expression of p53 and estrogen receptor in patients with node-negative breast cancer: results from IBCSG Trials VIII and IX. Breast Cancer Res. 2012;14:R143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Maeda T, Nakanishi Y, Hirotani Y, et al. Immunohistochemical co-expression status of cytokeratin 5/6, androgen receptor, and p53 as prognostic factors of adjuvant chemotherapy for triple negative breast cancer. Med Mol Morphol. 2016;49:11-21.

    Article  CAS  PubMed  Google Scholar 

  26. Jin MS, Park IA, Kim JY, et al. New insight on the biological role of p53 protein as a tumor suppressor: re-evaluation of its clinical significance in triple-negative breast cancer. Tumour Biol. 2016. doi:10.1007/s13277-016-4990-5.

  27. Thike AA, Cheok PY, Jara-Lazaro AR, Tan B, Tan P, Tan PH. Triple-negative breast cancer: clinicopathological characteristics and relationship with basal-like breast cancer. Mod Pathol. 2010;23:123-33.

    Article  CAS  PubMed  Google Scholar 

  28. Thangaraju M, Kaufmann SH, Couch FJ. BRCA1 facilitates stress-induced apoptosis in breast and ovarian cancer cell lines. J Biol Chem. 2000;275:33487-96.

    Article  CAS  PubMed  Google Scholar 

  29. Miyamoto K, Fukutomi T, Asada K, et al. Promoter hypermethylation and post-transcriptional mechanisms for reduced BRCA1 immunoreactivity in sporadic human breast cancers. Jpn J Clin Oncol. 2002;32:79-84.

    Article  PubMed  Google Scholar 

  30. Petitjean A, Achatz MI, Borresen-Dale AL, Hainaut P, Olivier M. TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene. 2007;26:2157-65.

    Article  CAS  PubMed  Google Scholar 

  31. Kim JY, Park K, Jung HH, et al. Association between mutation and expression of TP53 as a potential prognostic marker of triple-negative breast cancer. Cancer Res Treat. 2016. doi:10.4143/crt.2015.430.

  32. Thike AA, Tan PH, Ikeda M, Iqbal J. Increased ID4 expression, accompanied by mutant p53 accumulation and loss of BRCA1/2 proteins in triple-negative breast cancer, adversely affects survival. Histopathology. 2016;68:702-12.

    Article  PubMed  Google Scholar 

  33. Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO. Prognostic markers in triple-negative breast cancer. Cancer. 2007;109:25-32.

    Article  CAS  PubMed  Google Scholar 

  34. Olivier M, Langerod A, Carrieri P, et al. The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer. Clin Cancer Res. 2006;12:1157-67.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This study was supported by Medical Research Center Program (2015R1A5A2009124) through the National Research Foundation of Korea (NRF), Ministry of Science, ICT and Future Planning.

Conflict of Interest

The authors declared no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Young Kyung Bae MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, M.C., Choi, J.E., Lee, S.J. et al. Coexistent Loss of the Expressions of BRCA1 and p53 Predicts Poor Prognosis in Triple-Negative Breast Cancer. Ann Surg Oncol 23, 3524–3530 (2016). https://doi.org/10.1245/s10434-016-5307-z

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-016-5307-z

Keywords

Navigation