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
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
March-2018 Volume 52 Issue 3

Full Size Image

Cover Legend PDF

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
March-2018 Volume 52 Issue 3

Full Size Image

Cover Legend PDF

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

PITX2 DNA-methylation predicts response to anthracycline-based adjuvant chemotherapy in triple-negative breast cancer patients

  • Authors:
    • Magdalena Absmaier
    • Rudolf Napieralski
    • Tibor Schuster
    • Michaela Aubele
    • Axel Walch
    • Viktor Magdolen
    • Julia Dorn
    • Eva Gross
    • Nadia Harbeck
    • Aurelia Noske
    • Marion Kiechle
    • Manfred Schmitt
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Technische Universität München, Munich, Germany, Institute of Medical Statistics and Epidemiology, Technische Universität München, Munich, Germany, Institute of Pathology, Helmholtz Zentrum Muenchen, Neuherberg, Germany, Breast Center, Klinikum der Ludwig Maximilians Universität München, Munich, Germany, Department of Pathology and Pathological Anatomy, Technische Universität München, Munich, Germany
    Copyright: © Absmaier et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 755-767
    |
    Published online on: January 8, 2018
       https://doi.org/10.3892/ijo.2018.4241
  • 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

Triple-negative breast cancer (TNBC) constitutes a heterogeneous breast cancer subgroup with poor prognosis; survival rates are likely to be lower with TNBC compared to other breast cancer subgroups. For this disease, systemic adjuvant chemotherapy regimens often yield suboptimal clinical results. To improve treatment regimens in TNBC, identification of molecular biomarkers may help to select patients for individualized adjuvant therapy. Evidence has accumulated that determination of the methylation status of the PITX2 gene provides a predictive value in various breast cancer subgroups, either treated with endocrine-based therapy or anthracycline-containing chemotherapy. To further explore the validity of this novel predictive candidate biomarker, in the present exploratory retrospective study, determination of the PITX2 DNA-methylation status was assessed for non-metastatic TNBC patients treated with adjuvant anthracycline-based chemotherapy by molecular analysis of breast cancer tissues. The PITX2 DNA-methylation status was determined in fresh-frozen tumor tissue specimens (n=56) by methylation-specific qRT-PCR (qMSP) and the data related to disease-free and overall survival, applying an optimized DNA-methylation score of 6.35%. For non-metastatic TNBC patients treated with adjuvant systemic anthracycline-based chemotherapy, a low PITX2 DNA-methylation status (<6.35) defines TNBC patients with poor disease-free and overall survival. Univariate and multivariate analyses demonstrate the statistically independent predictive value of PITX2 DNA-methylation. For non-metastatic TNBC patients, selective determination of the PITX2 DNA-methylation status may serve as a cancer biomarker for predicting response to anthracycline-based adjuvant chemotherapy. The assay based on methylation of the PIXT2 gene can be applied to frozen and routinely available formalin-fixed, paraffin-embedded (FFPE) breast cancer tumor tissues that will not only define those TNBC patients who may benefit from anthracycline-based chemotherapy but also those who should be spared the necessity of such potentially toxic treatment. Such patients should be allocated to alternative treatment options.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, et al American Society of Clinical Oncology; College of American Pathologists: Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 31:3997–4013. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Bauer KR, Brown M, Cress RD, Parise CA and Caggiano V: Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: A population-based study from the California Cancer Registry. Cancer. 109:1721–1728. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Harbeck N and Gnant M: Breast cancer. Lancet. 389:1134–1150. 2017. View Article : Google Scholar

4 

Jiang T, Shi W, Wali VB, Pongor LS, Li C, Lau R, Győrffy B, Lifton RP, Symmans WF, Pusztai L, et al: Predictors of chemo-sensitivity in triple negative breast cancer: An integrated genomic analysis. PLoS Med. 13:e10021932016. View Article : Google Scholar

5 

Liedtke C and Kiesel L: Breast cancer molecular subtypes--modern therapeutic concepts for targeted therapy of a heterogeneous entity. Maturitas. 73:288–294. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Irshad S, Ellis P and Tutt A: Molecular heterogeneity of triple-negative breast cancer and its clinical implications. Curr Opin Oncol. 23:566–577. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Karn T, Pusztai L, Holtrich U, Iwamoto T, Shiang CY, Schmidt M, Müller V, Solbach C, Gaetje R, Hanker L, et al: Homogeneous datasets of triple negative breast cancers enable the identification of novel prognostic and predictive signatures. PLoS One. 6:e284032011. View Article : Google Scholar

8 

Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P and Narod SA: Triple-negative breast cancer: Clinical features and patterns of recurrence. Clin Cancer Res. 13:4429–4434. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, et al: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 98:10869–10874. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Lord CJ and Ashworth A: BRCAness revisited. Nat Rev Cancer. 16:110–120. 2016. View Article : Google Scholar : PubMed/NCBI

11 

Spugnesi L, Gabriele M, Scarpitta R, Tancredi M, Maresca L, Gambino G, Collavoli A, Aretini P, Bertolini I, Salvadori B, et al: Germline mutations in DNA repair genes may predict neoadjuvant therapy response in triple negative breast patients. Genes Chromosomes Cancer. 55:915–924. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Mori H, Kubo M, Nishimura R, Osako T, Arima N, Okumura Y, Okido M, Yamada M, Kai M, Kishimoto J, et al: BRCAness as a biomarker for predicting prognosis and response to anthracycline-based adjuvant chemotherapy for patients with triple-negative breast cancer. PLoS One. 11:e01670162016. View Article : Google Scholar : PubMed/NCBI

13 

Sharma P: Sharma. Oncologist. 21:1050–1062. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Lips EH, Mulder L, Oonk A, van der Kolk LE, Hogervorst FB, Imholz AL, Wesseling J, Rodenhuis S and Nederlof PM: Triple-negative breast cancer: BRCAness and concordance of clinical features with BRCA1-mutation carriers. Br J Cancer. 108:2172–2177. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Cardoso F, Harbeck N, Barrios CH, Bergh J, Cortés J, El Saghir N, Francis PA, Hudis CA, Ohno S, Partridge AH, et al: Research needs in breast cancer. Ann Oncol Nov. 28:208–217. 2017.

16 

Fleisher B, Clarke C and Ait-Oudhia S: Current advances in biomarkers for targeted therapy in triple-negative breast cancer. Breast Cancer (Dove Med Press). 8:183–197. 2016.

17 

Telli M: Optimizing chemotherapy in triple-negative breast cancer: The role of platinum. Am Soc Clin Oncol Educ Book. 33:e37–e42. 2014. View Article : Google Scholar

18 

Guan X, Ma F, Fan Y, Zhu W, Hong R and Xu B: Platinum-based chemotherapy in triple-negative breast cancer: A systematic review and meta-analysis of randomized-controlled trials. Anticancer Drugs. 26:894–901. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Anders CK, Abramson V, Tan T and Dent R: The evolution of triple-negative breast cancer: From biology to novel therapeutics. Am Soc Clin Oncol Educ Book. 35:34–42. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Gerratana L, Fanotto V, Pelizzari G, Agostinetto E and Puglisi F: Do platinum salts fit all triple negative breast cancers. Cancer Treat Rev. 48:34–41. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Kern P, Kalisch A, Kolberg HC, Kimmig R, Otterbach F, von Minckwitz G, Sikov WM, Pott D and Kurbacher C: Neoadjuvant, anthracycline-free chemotherapy with carboplatin and docetaxel in triple-negative, early-stage breast cancer: A multicentric analysis of feasibility and rates of pathologic complete response. Chemotherapy. 59:387–394. 2013. View Article : Google Scholar

22 

Zheng R, Han S, Duan C, Chen K, You Z, Jia J, Lin S, Liang L, Liu A, Long H, et al: Role of taxane and anthracycline combination regimens in the management of advanced breast cancer: a meta-analysis of randomized trials. Medicine. 94:e8032015. View Article : Google Scholar : PubMed/NCBI

23 

Adium R and Liedtke C: Neoadjuvant therapy for patients with triple negative breast cancer (TNBC). Rev Recent Clin Trials. 12:73–80. 2017. View Article : Google Scholar

24 

von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, Blohmer JU, Jackisch C, Paepke S, Gerber B, et al: Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): A randomised phase 2 trial. Lancet Oncol. 15:747–756. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Nabholtz JM, Abrial C, Mouret-Reynier MA, Dauplat MM, Weber B, Gligorov J, Forest AM, Tredan O, Vanlemmens L, Petit T, et al: Multicentric neoadjuvant phase II study of panitumumab combined with an anthracycline/taxane-based chemotherapy in operable triple-negative breast cancer: Identification of biologically defined signatures predicting treatment impact. Ann Oncol. 25:1570–1577. 2014. View Article : Google Scholar : PubMed/NCBI

26 

McClendon AK, Dean JL, Rivadeneira DB, Yu JE, Reed CA, Gao E, Farber JL, Force T, Koch WJ and Knudsen ES: CDK4/6 inhibition antagonizes the cytotoxic response to anthracycline therapy. Cell Cycle. 11:2747–2755. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Reinisch M, von Minckwitz G, Harbeck N, Janni W, Kümmel S, Kaufmann M, Elling D, Nekljudova V and Loibl S: Side effects of standard adjuvant and neoadjuvant chemotherapy regimens according to age groups in primary breast cancer. Breast Care (Basel). 8:60–66. 2013. View Article : Google Scholar

28 

Baylin SB and Jones PA: Epigenetic determinants of cancer. Cold Spring Harb Perspect Biol. 8:82016. View Article : Google Scholar

29 

Wu Y, Sarkissyan M and Vadgama JV: Epigenetics in breast and prostate cancer. Methods Mol Biol. 1238:425–466. 2015. View Article : Google Scholar :

30 

Atalay C: Atalay. Exp Oncol. 35:246–249. 2013.

31 

Jovanovic J, Rønneberg JA, Tost J and Kristensen V: The epigenetics of breast cancer. Mol Oncol. 4:242–254. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Basse C and Arock M: The increasing roles of epigenetics in breast cancer: Implications for pathogenicity, biomarkers, prevention and treatment. Int J Cancer. 137:2785–2794. 2015. View Article : Google Scholar

33 

Yang X, Lay F, Han H and Jones PA: Targeting DNA methylation for epigenetic therapy. Trends Pharmacol Sci. 31:536–546. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Jones PA: Jones. J Clin Invest. 124:14–16. 2014. View Article : Google Scholar : PubMed/NCBI

35 

Shiratori H, Yashiro K, Shen MM and Hamada H: Conserved regulation and role of Pitx2 in situs-specific morphogenesis of visceral organs. Development. 133:3015–3025. 2006. View Article : Google Scholar : PubMed/NCBI

36 

Wilting J and Hagedorn M: Left-right asymmetry in embryonic development and breast cancer: Common molecular determinants. Curr Med Chem. 18:5519–5527. 2011. View Article : Google Scholar

37 

Jezkova E, Kajo K, Zubor P, Grendar M, Malicherova B, Mendelova A, Dokus K, Lasabova Z, Plank L and Danko J: Methylation in promoter regions of PITX2 and RASSF1A genes in association with clinicopathological features in breast cancer patients. Tumour Biol. 37:15707–15718. 2016. View Article : Google Scholar

38 

Martens JW, Margossian AL, Schmitt M, Foekens J and Harbeck N: DNA methylation as a biomarker in breast cancer. Future Oncol. 5:1245–1256. 2009. View Article : Google Scholar : PubMed/NCBI

39 

Maier S, Nimmrich I, Koenig T, Eppenberger-Castori S, Bohlmann I, Paradiso A, Spyratos F, Thomssen C, Mueller V, Nährig J, et al European Organisation for Research and Treatment of Cancer (EORTC) PathoBiology group: DNA-methylation of the homeodomain transcription factor PITX2 reliably predicts risk of distant disease recurrence in tamoxifen-treated, node-negative breast cancer patients--Technical and clinical validation in a multi-centre setting in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC) PathoBiology group. Eur J Cancer. 43:1679–1686. 2007. View Article : Google Scholar : PubMed/NCBI

40 

Harbeck N, Nimmrich I, Hartmann A, Ross JS, Cufer T, Grützmann R, Kristiansen G, Paradiso A, Hartmann O, Margossian A, et al: Multicenter study using paraffin-embedded tumor tissue testing PITX2 DNA methylation as a marker for outcome prediction in tamoxifen-treated, node-negative breast cancer patients. J Clin Oncol. 26:5036–5042. 2008. View Article : Google Scholar : PubMed/NCBI

41 

Hartmann O, Spyratos F, Harbeck N, Dietrich D, Fassbender A, Schmitt M, Eppenberger-Castori S, Vuaroqueaux V, Lerebours F, Welzel K, et al: DNA methylation markers predict outcome in node-positive, estrogen receptor-positive breast cancer with adjuvant anthracycline-based chemotherapy. Clin Cancer Res. 15:315–323. 2009. View Article : Google Scholar : PubMed/NCBI

42 

Nimmrich I, Sieuwerts AM, Meijer-van Gelder ME, Schwope I, Bolt-de Vries J, Harbeck N, Koenig T, Hartmann O, Kluth A, Dietrich D, et al: DNA hypermethylation of PITX2 is a marker of poor prognosis in untreated lymph node-negative hormone receptor-positive breast cancer patients. Breast Cancer Res Treat. 111:429–437. 2008. View Article : Google Scholar

43 

Kumar P and Aggarwal R: An overview of triple-negative breast cancer. Arch Gynecol Obstet. 293:247–269. 2016. View Article : Google Scholar

44 

Loibl S, Denkert C and von Minckwitz G: Neoadjuvant treatment of breast cancer - Clinical and research perspective. Breast. 24(Suppl 2): S73–S77. 2015. View Article : Google Scholar

45 

Liedtke C and Rody A: New treatment strategies for patients with triple-negative breast cancer. Curr Opin Obstet Gynecol. 27:77–84. 2015. View Article : Google Scholar

46 

Yfanti C, Mengele K, Gkazepis A, Weirich G, Giersig C, Kuo WL, Tang WJ, Rosner M and Schmitt M: Expression of metalloprotease insulin-degrading enzyme insulysin in normal and malignant human tissues. Int J Mol Med. 22:421–431. 2008.PubMed/NCBI

47 

Schmitt M, Mengele K, Schueren E, Sweep FC, Foekens JA, Brünner N, Laabs J, Malik A and Harbeck N; European Organisation for Research and Treatment of Cancer Pathobiology Group: European Organisation for Research and Treatment of Cancer (EORTC) Pathobiology Group standard operating procedure for the preparation of human tumour tissue extracts suited for the quantitative analysis of tissue-associated biomarkers. Eur J Cancer. 43:835–844. 2007. View Article : Google Scholar : PubMed/NCBI

48 

McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M and Clark GM; Statistics Subcommittee of the NCI-EORTC Working Group on Cancer Diagnostics: Reporting recommendations for tumor marker prognostic studies (REMARK). J Natl Cancer Inst. 97:1180–1184. 2005. View Article : Google Scholar : PubMed/NCBI

49 

Altman DG, McShane LM, Sauerbrei W and Taube SE: Reporting recommendations for tumor marker prognostic studies REMARK. Explanation and elaboration. PLoS Med. 9:e10012162012. View Article : Google Scholar

50 

Hothorn T: Maxstat: maximally selected rank statistics. R package version 0.7-14.

51 

Team RD CR: A language and environment for statistical computing. R Foundation for Statistical Computing Vienna Austria: 2012

52 

Blum M, Feistel K, Thumberger T and Schweickert A: The evolution and conservation of left-right patterning mechanisms. Development. 141:1603–1613. 2014. View Article : Google Scholar : PubMed/NCBI

53 

Tabin CJ: Tabin. Cell. 127:27–32. 2006. View Article : Google Scholar : PubMed/NCBI

54 

Levin M: Levin. Mech Dev. 122:3–25. 2005. View Article : Google Scholar

55 

Paska AV and Hudler P: Aberrant methylation patterns in cancer: A clinical view. Biochem Med (Zagreb). 25:161–176. 2015. View Article : Google Scholar

56 

Ahmed D, Danielsen SA, Aagesen TH, Bretthauer M, Thiis-Evensen E, Hoff G, Rognum TO, Nesbakken A, Lothe RA and Lind GE: A tissue-based comparative effectiveness analysis of biomarkers for early detection of colorectal tumors. Clin Transl Gastroenterol. 3:e272012. View Article : Google Scholar

57 

Berghoff AS, Hainfellner JA, Marosi C and Preusser M: Assessing MGMT methylation status and its current impact on treatment in glioblastoma. CNS Oncol. 4:47–52. 2015. View Article : Google Scholar : PubMed/NCBI

58 

Darwiche K, Zarogoulidis P, Baehner K, Welter S, Tetzner R, Wohlschlaeger J, Theegarten D, Nakajima T and Freitag L: Assessment of SHOX2 methylation in EBUS-TBNA specimen improves accuracy in lung cancer staging. Ann Oncol. 24:2866–2870. 2013. View Article : Google Scholar : PubMed/NCBI

59 

Dietrich D, Jung M, Puetzer S, Leisse A, Holmes EE, Meller S, Uhl B, Schatz P, Ivascu C and Kristiansen G: Diagnostic and prognostic value of SHOX2 and SEPT9 DNA methylation and cytology in benign, paramalignant and malignant pleural effusions. PLoS One. 8:e842252013. View Article : Google Scholar

60 

Ilse P, Biesterfeld S, Pomjanski N, Wrobel C and Schramm M: Analysis of SHOX2 methylation as an aid to cytology in lung cancer diagnosis. Cancer Genomics Proteomics. 11:251–258. 2014.PubMed/NCBI

61 

Székely B, Silber AL and Pusztai L: New therapeutic strategies for triple-negative breast cancer. Oncology (Williston Park). 31:130–137. 2017.

62 

Fung FK, Chan DW, Liu VW, Leung TH, Cheung AN and Ngan HY: Increased expression of PITX2 transcription factor contributes to ovarian cancer progression. PLoS One. 7:e370762012. View Article : Google Scholar : PubMed/NCBI

63 

Kapoor S: Kapoor. APMIS. 121:10112013. View Article : Google Scholar

64 

Liu Y, Huang Y and Zhu GZ: Cyclin A1 is a transcriptional target of PITX2 and overexpressed in papillary thyroid carcinoma. Mol Cell Biochem. 384:221–227. 2013. View Article : Google Scholar : PubMed/NCBI

65 

Toyota M, Kopecky KJ, Toyota MO, Jair KW, Willman CL and Issa JP: Methylation profiling in acute myeloid leukemia. Blood. 97:2823–2829. 2001. View Article : Google Scholar : PubMed/NCBI

66 

Uhl B, Gevensleben H, Tolkach Y, Sailer V, Majores M, Jung M, Meller S, Stein J, Ellinger J, Dietrich D, et al: PITX2 DNA Methylation as biomarker for individualized risk assessment of prostate cancer in core biopsies. J Mol Diagn. 19:107–114. 2017. View Article : Google Scholar

67 

Wang Q, Li J, Wu W, Shen R, Jiang H, Qian Y, Tang Y, Bai T, Wu S, Wei L, et al: Smad4-dependent suppressor pituitary homeobox 2 promotes PPP2R2A-mediated inhibition of Akt pathway in pancreatic cancer. Oncotarget. 7:11208–11222. 2016.PubMed/NCBI

68 

Zhang JX, Chen ZH, Xu Y, Chen JW, Weng HW, Yun M, Zheng ZS, Chen C, Wu BL, Li EM, et al: Downregulation of microRNA-644a promotes esophageal squamous cell carcinoma aggressiveness and stem cell-like phenotype via dysregulation of PITX2. Clin Cancer Res. 23:298–310. 2017. View Article : Google Scholar

69 

Zhang JX, Tong ZT, Yang L, Wang F, Chai HP, Zhang F, Xie MR, Zhang AL, Wu LM, Hong H, et al: PITX2: A promising predictive biomarker of patients' prognosis and chemoradioresistance in esophageal squamous cell carcinoma. Int J Cancer. 132:2567–2577. 2013. View Article : Google Scholar

70 

Sailer V, Gevensleben H, Dietrich J, Goltz D, Kristiansen G, Bootz F and Dietrich D: Clinical performance validation of PITX2 DNA methylation as prognostic biomarker in patients with head and neck squamous cell carcinoma. PLoS One. 12:e01794122017. View Article : Google Scholar : PubMed/NCBI

71 

López JI, Angulo JC, Martín A, Sánchez-Chapado M, González-Corpas A, Colás B and Ropero S: A DNA hypermethylation profile reveals new potential biomarkers for the evaluation of prognosis in urothelial bladder cancer. APMIS. 125:787–796. 2017. View Article : Google Scholar : PubMed/NCBI

72 

Harris LN, Ismaila N, McShane LM, Andre F, Collyar DE, Gonzalez-Angulo AM, Hammond EH, Kuderer NM, Liu MC, Mennel RG, et al: American Society of Clinical Oncology: Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 34:1134–1150. 2016. View Article : Google Scholar : PubMed/NCBI

73 

Wan Abdul, Rahman WF, Fauzi MH and Jaafar H: Expression of DNA methylation marker of paired-like homeodomain transcription factor 2 and growth receptors in invasive ductal carcinoma of the breast. Asian Pac J Cancer Prev. 15:8441–8445. 2014. View Article : Google Scholar

74 

Bologna-Molina R, Mikami T, Pereira-Prado V, Pires FR, Carlos-Bregni R and Mosqueda-Taylor A: Primordial odonto-genic tumor: An immunohistochemical profile. Med Oral Patol Oral Cir Bucal. 22:e314-e3232017.

75 

Huang Y, Guigon CJ, Fan J, Cheng SY and Zhu GZ: Pituitary homeobox 2 (PITX2) promotes thyroid carcinogenesis by activation of cyclin D2. Cell Cycle. 9:1333–1341. 2010. View Article : Google Scholar : PubMed/NCBI

76 

Denkert C, Liedtke C, Tutt A and von Minckwitz G: Molecular alterations in triple-negative breast cancer-the road to new treatment strategies. Lancet. 389:2430–2442. 2016. View Article : Google Scholar : PubMed/NCBI

77 

Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y and Pietenpol JA: 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

78 

Ring BZ, Hout DR, Morris SW, Lawrence K, Schweitzer BL, Bailey DB, Lehmann BD, Pietenpol JA and Seitz RS: Generation of an algorithm based on minimal gene sets to clinically subtype triple negative breast cancer patients. BMC Cancer. 16:1432016. View Article : Google Scholar : PubMed/NCBI

79 

Bianchini G, Balko JM, Mayer IA, Sanders ME and Gianni L: Triple-negative breast cancer: Challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. 13:674–690. 2016. View Article : Google Scholar : PubMed/NCBI

80 

Yadav BS, Sharma SC, Chanana P and Jhamb S: Systemic treatment strategies for triple-negative breast cancer. World J Clin Oncol. 5:125–133. 2014. View Article : Google Scholar : PubMed/NCBI

81 

Burstein HJ: Patients with triple negative breast cancer: Is there an optimal adjuvant treatment? Breast. 22(Suppl 2): S147–S148. 2013. View Article : Google Scholar : PubMed/NCBI

82 

Christenson ES, James T, Agrawal V and Park BH: Use of biomarkers for the assessment of chemotherapy-induced cardiac toxicity. Clin Biochem. 48:223–235. 2015. View Article : Google Scholar :

83 

Basso SM, Santeufemia DA, Fadda GM, Tozzoli R, D'Aurizio F and Lumachi F: Advances in the treatment of triple-negative early breast cancer. Med Chem. 12:268–272. 2016. View Article : Google Scholar

84 

Wahba HA and El-Hadaad HA: Current approaches in treatment of triple-negative breast cancer. Cancer Biol Med. 12:106–116. 2015.PubMed/NCBI

85 

Yao H, He G, Yan S, Chen C, Song L, Rosol TJ and Deng X: Triple-negative breast cancer: Is there a treatment on the horizon. Oncotarget. 8:1913–1924. 2017.

86 

Locatelli MA, Curigliano G and Eniu A: Extended adjuvant chemotherapy in triple-negative breast cancer. Breast Care (Basel). 12:152–158. 2017. View Article : Google Scholar

87 

Liedtke C, Thill M, Jackisch C, Thomssen C, Müller V and Janni W: AGO Recommendations for the diagnosis and treatment of patients with early breast cancer: Update. Breast Care (Basel). 12. pp. 172–183. 2017, View Article : Google Scholar

88 

Mori H, Kubo M, Nishimura R, Osako T, Arima N, Okumura Y, Okido M, Yamada M, Kai M, Kishimoto J, et al: BRCAness as a biomarker for predicting prognosis and response to anthracycline-based adjuvant chemotherapy for patients with triple-negative breast cancer. PLoS One. 11:e01670162016. View Article : Google Scholar : PubMed/NCBI

89 

Bouchalova K, Svoboda M, Kharaishvili G, Vrbkova J, Bouchal J, Trojanec R, Koudelakova V, Radova L, Cwiertka K, Hajduch M, et al: BCL2 is an independent predictor of outcome in basal-like triple-negative breast cancers treated with adjuvant anthracycline-based chemotherapy. Tumour Biol. 36:4243–4252. 2015. View Article : Google Scholar : PubMed/NCBI

90 

Duffy MJ, Napieralski R, Martens JW, Span PN, Spyratos F, Sweep FC, Brunner N, Foekens JA and Schmitt M; EORTC PathoBiology Group: Methylated genes as new cancer biomarkers. Eur J Cancer. 45:335–346. 2009. View Article : Google Scholar : PubMed/NCBI

91 

Pillai SG, Dasgupta N, Siddappa CM, Watson MA, Fleming T, Trinkaus K and Aft R: Paired-like Homeodomain Transcription factor 2 expression by breast cancer bone marrow disseminated tumor cells is associated with early recurrent disease development. Breast Cancer Res Treat. 153:507–517. 2015. View Article : Google Scholar : PubMed/NCBI

92 

Dietrich D, Hasinger O, Liebenberg V, Field JK, Kristiansen G and Soltermann A: DNA methylation of the homeobox genes PITX2 and SHOX2 predicts outcome in non-small-cell lung cancer patients. Diagn Mol Pathol. 21:93–104. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Absmaier M, Napieralski R, Schuster T, Aubele M, Walch A, Magdolen V, Dorn J, Gross E, Harbeck N, Noske A, Noske A, et al: PITX2 DNA-methylation predicts response to anthracycline-based adjuvant chemotherapy in triple-negative breast cancer patients. Int J Oncol 52: 755-767, 2018.
APA
Absmaier, M., Napieralski, R., Schuster, T., Aubele, M., Walch, A., Magdolen, V. ... Schmitt, M. (2018). PITX2 DNA-methylation predicts response to anthracycline-based adjuvant chemotherapy in triple-negative breast cancer patients. International Journal of Oncology, 52, 755-767. https://doi.org/10.3892/ijo.2018.4241
MLA
Absmaier, M., Napieralski, R., Schuster, T., Aubele, M., Walch, A., Magdolen, V., Dorn, J., Gross, E., Harbeck, N., Noske, A., Kiechle, M., Schmitt, M."PITX2 DNA-methylation predicts response to anthracycline-based adjuvant chemotherapy in triple-negative breast cancer patients". International Journal of Oncology 52.3 (2018): 755-767.
Chicago
Absmaier, M., Napieralski, R., Schuster, T., Aubele, M., Walch, A., Magdolen, V., Dorn, J., Gross, E., Harbeck, N., Noske, A., Kiechle, M., Schmitt, M."PITX2 DNA-methylation predicts response to anthracycline-based adjuvant chemotherapy in triple-negative breast cancer patients". International Journal of Oncology 52, no. 3 (2018): 755-767. https://doi.org/10.3892/ijo.2018.4241
Copy and paste a formatted citation
x
Spandidos Publications style
Absmaier M, Napieralski R, Schuster T, Aubele M, Walch A, Magdolen V, Dorn J, Gross E, Harbeck N, Noske A, Noske A, et al: PITX2 DNA-methylation predicts response to anthracycline-based adjuvant chemotherapy in triple-negative breast cancer patients. Int J Oncol 52: 755-767, 2018.
APA
Absmaier, M., Napieralski, R., Schuster, T., Aubele, M., Walch, A., Magdolen, V. ... Schmitt, M. (2018). PITX2 DNA-methylation predicts response to anthracycline-based adjuvant chemotherapy in triple-negative breast cancer patients. International Journal of Oncology, 52, 755-767. https://doi.org/10.3892/ijo.2018.4241
MLA
Absmaier, M., Napieralski, R., Schuster, T., Aubele, M., Walch, A., Magdolen, V., Dorn, J., Gross, E., Harbeck, N., Noske, A., Kiechle, M., Schmitt, M."PITX2 DNA-methylation predicts response to anthracycline-based adjuvant chemotherapy in triple-negative breast cancer patients". International Journal of Oncology 52.3 (2018): 755-767.
Chicago
Absmaier, M., Napieralski, R., Schuster, T., Aubele, M., Walch, A., Magdolen, V., Dorn, J., Gross, E., Harbeck, N., Noske, A., Kiechle, M., Schmitt, M."PITX2 DNA-methylation predicts response to anthracycline-based adjuvant chemotherapy in triple-negative breast cancer patients". International Journal of Oncology 52, no. 3 (2018): 755-767. https://doi.org/10.3892/ijo.2018.4241
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