Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
June-2014 Volume 7 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2014 Volume 7 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

O6‑methylguanine‑DNA methyltransferase as a prognostic and predictive marker for basal‑like breast cancer treated with cyclophosphamide‑based chemotherapy

  • Authors:
    • Sayuri Isono
    • Makoto Fujishima
    • Tatsuya Azumi
    • Yukihiko Hashimoto
    • Yoshifumi Komoike
    • Masao Yukawa
    • Masahiro Watatani
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Faculty of Medicine, Kinki University, Osaka‑Sayama, Osaka 589‑8511, Japan, Department of Gastroenterological and Breast Surgery, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino, Osaka 583‑8588, Japan, Department of Breast and Endocrine Surgery, Faculty of Medicine Nara Hospital, Kinki University, Ikoma, Nara 630‑0293, Japan
  • Pages: 1778-1784
    |
    Published online on: March 20, 2014
       https://doi.org/10.3892/ol.2014.1985
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The O6‑methylguanine‑DNA methyltransferase (MGMT) protein protects cells from alkylating agents by removing alkyl groups from the O6‑position of guanine. However, its effect on DNA damage induced by cyclophosphamide (CPM) is unclear. The present study investigated whether MGMT expression was correlated with prognosis in patients with breast cancer that was managed according to a common therapeutic protocol or treated with CPM‑based chemotherapy. The intrinsic subtypes and MGMT protein expression levels were assessed in 635 consecutive patients with breast cancer using immunohistochemistry. In total, 425 (67%) luminal A, 95 (15%) luminal B, 47 (7%) human epidermal growth factor receptor‑2+/estrogen receptor- (HER2+/ER‑) and 48 (8%) basal‑like subtypes were identified. Of these, MGMT positivity was identified in 398 (63%) of 635 breast cancers; 68% of luminal A, 67% of luminal B, 30% of HER2+/ER‑ and 46% of basal‑like subtypes were positive. The overall survival (OS) and disease‑free survival (DFS) rates did not significantly differ according to the MGMT status among patients with luminal A, luminal B or HER2+/ER‑ subtypes, and patients with MGMT‑negative basal‑like cancers tended to have a longer DFS, but not a significantly longer OS time. CPM‑containing chemotherapy was administered to 26%, 40%, 47% and 31% of patients with luminal A, luminal B, HER2+/ER‑ and basal‑like tumors, respectively. Although the MGMT status and clinical outcomes of patients with the luminal A, luminal B or HER2+/ER‑ subtypes treated with CPM were not significantly correlated, the patients with MGMT‑negative basal‑like tumors who received CPM exhibited significantly improved DFS and OS compared with the CPM‑treated patients with MGMT‑positive tumors. MGMT may be a useful prognostic and predictive marker for CPM‑containing chemotherapy in basal‑like breast cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Pegg A: Multifaceted roles of alkyltransferase and related proteins in DNA repair, DNA damage, resistance to chemotherapy, and research tools. Chem Res Toxicol. 24:618–639. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Colvin M and Hilton J: Pharmacology of cyclophosphamide and metabolites. Cancer Treat Rep. 65(Suppl 3): 89–95. 1981.

3 

Mattern J, Eichhorn U, Kaina B and Volm M: O6-methylguanine-DNA methyltransferase activity and sensitivity to cyclophosphamide and cisplatin in human lung tumor xenografts. Int J Cancer. 77:919–922. 1998. View Article : Google Scholar : PubMed/NCBI

4 

D’Incalci M, Bonfanti M, Pifferi A, et al: The antitumour activity of alkylating agents is not correlated with the levels of glutathione, glutathione transferase and O6-alkylguanine-DNA-alkyltransferase of human tumour xenografts. EORTC SPG and PAMM Groups. Eur J Cancer. 34:1749–1755. 1998.

5 

Ohno T, Hiraga J, Ohashi H, et al: Loss of O6-methylguanine-DNA-methyltransferase protein expression is a favorable prognostic marker in diffuse large B-cell lymphoma. Int J Hematol. 83:341–347. 2006. View Article : Google Scholar

6 

Hansen RJ, Ludeman SM, Paikoff SJ, et al: Role of MGMT in protecting against cyclophosphamide-induced toxicity in cells and animals. DNA repair (Amst). 6:1145–1154. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Cayre A, Penault-Llorca F, De Latour M, et al: O(6)-methyguanine-DNA methyl transferase gene expression and prognosis in breast carcinoma. Int J Oncol. 21:1125–1131. 2002.PubMed/NCBI

8 

Nakai K, Mitomi H, Alkam Y, et al: Predictive value of MGMT, hMLH1, hMSH2 and BRCA1 protein expression for pathological complete response to neoadjuvant chemotherapy in basal-like breast cancer patients. Cancer Chemother Pharmacol. 69:923–930. 2012. View Article : Google Scholar

9 

Esteller M, Hamilton SR, Burger PC, et al: Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res. 59:793–797. 1999.PubMed/NCBI

10 

Wani G and D’Ambrosio SM: Expression of the O6-alkylguanine-DNA alkyltransferase gene is elevated in human breast tumor cells. Anticancer Res. 17:4311–4315. 1997.PubMed/NCBI

11 

Citron M, Schoenhaus M, Rothenberg H, et al: O6-methylguanine-DNA methyltransferase in normal and malignant tissue of the breast. Cancer Invest. 12:605–610. 1994. View Article : Google Scholar : PubMed/NCBI

12 

Osanai T, Takagi Y, Toriya Y, et al: Inverse correlation between the expression of O6-methylguanine-DNA methyl transferase (MGMT) and p53 in breast cancer. Jpn J Clin Oncol. 35:121–125. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Matsukura S, Miyazaki K, Yakushiji H, et al: Expression and prognostic significance of O6-methylguanine-DNA methyltransferase in hepatocellular, gastric, and breast cancers. Ann Surg Oncol. 8:807–816. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Neto JC, Ikoma MM, Carvalho KC, et al: MGMT and PTEN as potential prognostic markers in breast cancer. Exp Mol Pathol. 92:20–26. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Clemons MJ, Bibby MC, El Teraifi H, et al: Heterogeneity of O6-alkylguanine-DNA-alkyltransferase expression in human breast tumours. Br J Cancer. 86:1797–1802. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Perou CM, Sørlie T, Eisen MB, et al: Molecular portraits of human breast tumours. Nature. 406:747–752. 2000. View Article : Google Scholar : PubMed/NCBI

17 

Sørlie T, Perou CM, Tibshirani R, et al: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 98:10869–10874. 2001.PubMed/NCBI

18 

Prat A, Ellis MJ and Perou CM: Practical implications of gene-expression-based assays for breast oncologists. Nat Rev Clin Oncol. 9:48–57. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Fumagalli C, Pruneri G, Possanzini P, et al: Methylation of O6-methylguanine-DNA methyltransferase (MGMT) promoter gene in triple-negative breast cancer patients. Breast Cancer Res Treat. 134:131–137. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Wolff AC, Hammond ME, Schwartz JN, et al: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 25:118–1145. 2007. View Article : Google Scholar

21 

Livasy CA, Karaca G, Nanda R, et al: Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Modern Pathol. 19:264–271. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Kim MJ, Ro JY, Ahn SH, et al: Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes. Hum Pathol. 37:1217–1226. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Nakasu S, Fukami T, Baba K and Matsuda M: Immunohistochemical study for O6-methylguanine-DNA methyltransferase in the non-neoplastic and neoplastic components of glioma. J Neurooncol. 70:333–340. 2004. View Article : Google Scholar : PubMed/NCBI

24 

Carey LA, Perou CM, Livasy CA, et al: Race, Breast Cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 295:2492–2502. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Munot K, Bell SM, Lane S, et al: Pattern of expression of genes linked to epigenetic silencing in human breast cancer. Hum Pathol. 37:989–999. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Sharma G, Mirza S, Parshad R, et al: Clinical significance of promoter hypermethylation of DNA repair genes in tumor and serum DNA in invasive ductal breast carcinoma patients. Life Sci. 87:83–91. 2010. View Article : Google Scholar : PubMed/NCBI

27 

O’Malley FP, Chia S, Tu D, et al: Topoisomerase II alpha and responsiveness of breast cancer to adjuvant chemotherapy. J Natl Cancer Inst. 101:644–650. 2009.

28 

Colleoni M, Cole BF, Viale G, et al: Classical cyclophosphamide, methotrexate, and fluorouracil chemotherapy is more effective in triple-negative, node-negative breast cancer: results from two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Clin Oncol. 28:2966–2973. 2010. View Article : Google Scholar

29 

Falo C, Moreno A, Varela M, et al: HER-2/neu ststus and response to CMF: retrospective study in a series of operable breast cancer treated with primary CMF chemotherapy. J Cancer Res Clin Oncol. 133:423–429. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Munzone E, Curigliano G, Burstein HJ, et al: CMF revisited in the 21st century. Ann Oncol. 23:305–311. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Cai Y, Wu MH, Ludeman SM, et al: Role of O6-alkylguanine-DNA alkyltransferase in protecting against cyclophosphamide-induced toxicity and mutagenicity. Cancer Res. 59:3059–3063. 1999.PubMed/NCBI

32 

Gamcsik MP, Dolan ME, Andersson BS and Murray D: Mechanisms of resistance to the toxicity of cyclophosphamide. Curr Pharm Des. 5:587–605. 1999.PubMed/NCBI

33 

Hilton J: Role of aldehyde dehydrogenase in cyclophosphamide-resistance L1210 leukemia. Cancer Res. 44:5156–5160. 1984.PubMed/NCBI

34 

Kirsch DG and Kastan MB: Tumor-suppressor p53: implication for tumor development and prognosis. J Clin Oncol. 16:3158–3168. 1998.PubMed/NCBI

35 

Lehmann BD, Bauer JA, Chen X, et al: Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 121:2750–2767. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Isono S, Fujishima M, Azumi T, Hashimoto Y, Komoike Y, Yukawa M and Watatani M: O6‑methylguanine‑DNA methyltransferase as a prognostic and predictive marker for basal‑like breast cancer treated with cyclophosphamide‑based chemotherapy. Oncol Lett 7: 1778-1784, 2014.
APA
Isono, S., Fujishima, M., Azumi, T., Hashimoto, Y., Komoike, Y., Yukawa, M., & Watatani, M. (2014). O6‑methylguanine‑DNA methyltransferase as a prognostic and predictive marker for basal‑like breast cancer treated with cyclophosphamide‑based chemotherapy. Oncology Letters, 7, 1778-1784. https://doi.org/10.3892/ol.2014.1985
MLA
Isono, S., Fujishima, M., Azumi, T., Hashimoto, Y., Komoike, Y., Yukawa, M., Watatani, M."O6‑methylguanine‑DNA methyltransferase as a prognostic and predictive marker for basal‑like breast cancer treated with cyclophosphamide‑based chemotherapy". Oncology Letters 7.6 (2014): 1778-1784.
Chicago
Isono, S., Fujishima, M., Azumi, T., Hashimoto, Y., Komoike, Y., Yukawa, M., Watatani, M."O6‑methylguanine‑DNA methyltransferase as a prognostic and predictive marker for basal‑like breast cancer treated with cyclophosphamide‑based chemotherapy". Oncology Letters 7, no. 6 (2014): 1778-1784. https://doi.org/10.3892/ol.2014.1985
Copy and paste a formatted citation
x
Spandidos Publications style
Isono S, Fujishima M, Azumi T, Hashimoto Y, Komoike Y, Yukawa M and Watatani M: O6‑methylguanine‑DNA methyltransferase as a prognostic and predictive marker for basal‑like breast cancer treated with cyclophosphamide‑based chemotherapy. Oncol Lett 7: 1778-1784, 2014.
APA
Isono, S., Fujishima, M., Azumi, T., Hashimoto, Y., Komoike, Y., Yukawa, M., & Watatani, M. (2014). O6‑methylguanine‑DNA methyltransferase as a prognostic and predictive marker for basal‑like breast cancer treated with cyclophosphamide‑based chemotherapy. Oncology Letters, 7, 1778-1784. https://doi.org/10.3892/ol.2014.1985
MLA
Isono, S., Fujishima, M., Azumi, T., Hashimoto, Y., Komoike, Y., Yukawa, M., Watatani, M."O6‑methylguanine‑DNA methyltransferase as a prognostic and predictive marker for basal‑like breast cancer treated with cyclophosphamide‑based chemotherapy". Oncology Letters 7.6 (2014): 1778-1784.
Chicago
Isono, S., Fujishima, M., Azumi, T., Hashimoto, Y., Komoike, Y., Yukawa, M., Watatani, M."O6‑methylguanine‑DNA methyltransferase as a prognostic and predictive marker for basal‑like breast cancer treated with cyclophosphamide‑based chemotherapy". Oncology Letters 7, no. 6 (2014): 1778-1784. https://doi.org/10.3892/ol.2014.1985
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team