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Annals of Surgical Oncology

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01-10-2016 | Breast Oncology

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

Authors: Min Chong Kim, MD, Jung Eun Choi, MD, Soo Jung Lee, MD, PhD, Young Kyung Bae, MD, PhD

Published in: Annals of Surgical Oncology | Issue 11/2016

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.

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRef

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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

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.CrossRefPubMed

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.PubMed

11.

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

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.PubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

17.

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

18.

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

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

Title: Coexistent Loss of the Expressions of BRCA1 and p53 Predicts Poor Prognosis in Triple-Negative Breast Cancer
Authors: Min Chong Kim, MD
Jung Eun Choi, MD
Soo Jung Lee, MD, PhD
Young Kyung Bae, MD, PhD
Publication date: 01-10-2016
Publisher: Springer International Publishing
Published in: Annals of Surgical Oncology / Issue 11/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-016-5307-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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