International Journal of Clinical Oncology

, Volume 11, Issue 6, pp 426–433

p53 expression status is a significant molecular marker in predicting the time to endocrine therapy failure in recurrent breast cancer: a cohort study

  • Kazuharu Kai
  • Reiki Nishimura
  • Nobuyuki Arima
  • Haruhiko Miyayama
  • Hirotaka Iwase
ORIGINAL ARTICLE

Abstract

Background

Hormone receptor status has been one of the most important factors in predicting the response to endocrine therapy in breast cancer patients. However, half of those patients with estrogen receptor-positive tumors do not respond to endocrine therapy. There have been no universal factors for predicting resistance to endocrine therapy in this population. Recently, p53 status has been extensively used as a predictive factor for response to systemic therapy, because tumor cells lacking p53 function do not respond to systemic therapy due to a failure in apoptosis. We therefore studied the relationship between the efficacy of endocrine therapy and biological factors, including p53.

Methods

The expression of p53, Ki67, and human epidermal growth factor receptor (HER)2 was examined by immunostaining in the primary tumors of 53 patients who received endocrine therapy for recurrent or advanced breast cancer. The following clinical factors were also analyzed: site treated, disease-free interval, and response to first-line endocrine therapy. To evaluate the significance of these factors, time to endocrine therapy failure (TTEF), or the total duration of sequential endocrine therapies was adopted as representing the clinical outcome.

Results

The median TTEF was 16.1 months (range, 2.5–89.9 months). Multivariate analysis showed significantly reduced TTEF associated with no response to first-line endocrine therapy (P = 0.006 and P = 0.002 in all patients and in recurrent patients, respectively) and associated with positive p53 expression (P = 0.066 and P = 0.004, respectively).

Conclusion

p53 expression status was a significant molecular marker as well as the response to first-line endocrine therapy for predicting TTEF in recurrent breast cancer with hormone-sensitive disease.

Key words

Time to endocrine therapy failure Response to first-line endocrine therapy p53 expression status 

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References

  1. 1.
    Ciocca, DR, Elledge, R 2000Molecular markers for predicting response to tamoxifen in breast cancer patientsEndocrine13110PubMedCrossRefGoogle Scholar
  2. 2.
    Kardinal, CG 2002

    Hormonal and endocrine therapy of breast cancer

    Donegan, WLSpratt, JS eds. Cancer of the breast, fifth ednElsevier ScienceSt. Louis693737
    Google Scholar
  3. 3.
    Ring, AE, Ellis, PA 2002Predictors of response to systemic therapy in breast cancerForum Genova121932PubMedGoogle Scholar
  4. 4.
    Osborne, CK, Shou, J, Massarweh, S,  et al. 2005Crosstalk between estrogen receptor and growth factor receptor pathways as a cause for endocrine therapy resistance in breast cancerClin Cancer Res11865870Google Scholar
  5. 5.
    Arpino, G, Green, SJ, Allred, DC,  et al. 2004HER2 amplification, HER-1 expression, and tamoxifen response in estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group studyClin Cancer Res1056705676PubMedCrossRefGoogle Scholar
  6. 6.
    Ellis, MJ, Coop, A, Singh, B,  et al. 2001Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trialJ Clin Oncol1938083816PubMedGoogle Scholar
  7. 7.
    Dixon, JM, Jackson, J, Hills, M,  et al. 2004Anastrozole demonstrates clinical and biological effectiveness in oestrogen receptor-positive breast cancers, irrespective of the erbB2 statusEur J Cancer4027422747PubMedCrossRefGoogle Scholar
  8. 8.
    Berns, EM, Foekens, JA, Vossen, R,  et al. 2000Complete sequencing of TP53 predicts poor response to systemic therapy of advanced breast cancerCancer Res6021552162PubMedGoogle Scholar
  9. 9.
    Fitzgibbons, PL, Page, DL, Weaver, D,  et al. 2000Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999Arch Pathol Lab Med124966978PubMedGoogle Scholar
  10. 10.
    Hortobagyi, GN 1998Treatment of breast cancerN Engl J Med339974984PubMedCrossRefGoogle Scholar
  11. 11.
    Hayward, JL, Carbone, PP, Heuson, JC,  et al. 1977Assessment of response to therapy in advanced breast cancer: a project of the Programme on Clinical Oncology of the International Union Against Cancer, Geneva, SwitzerlandCancer3912891294PubMedCrossRefGoogle Scholar
  12. 12.
    de Haes, H, Olschewski, M, Kaufmann, M,  et al. 2003Quality of life in goserelin-treated versus cyclophosphamide + methotrexate + fluorouracil-treated premenopausal and perimenopausal patients with node-positive, early breast cancer: the Zoladex Early Breast Cancer Research Association Trialists GroupJ Clin Oncol2145104516PubMedCrossRefGoogle Scholar
  13. 13.
    Piccart, M, Parker, LM, Pritchard, KI 2003Oestrogen receptor downregulation: an opportunity for extending the window of endocrine therapy in advanced breast cancerAnn Oncol1410171025PubMedCrossRefGoogle Scholar
  14. 14.
    Shimozuma, K, Sonoo, H, Ichihara, K 1995Analysis of the factors influencing the quality of life of patients with advanced or recurrent breast cancerSurg Today25874882PubMedCrossRefGoogle Scholar
  15. 15.
    Kurebayashi, J, Sonoo, H, Inaji, H,  et al. 2000Endocrine therapies for patients with recurrent breast cancer: predictive factors for responses to first- and second-line endocrine therapiesOncology593137PubMedCrossRefGoogle Scholar
  16. 16.
    Archer, SG, Eliopoulos, A, Spandidos, D,  et al. 1995Expression of ras parn21, p53 and c-erbB-2 in advanced breast cancer and response to first line hormonal therapyBr J Cancer7212591266PubMedGoogle Scholar
  17. 17.
    Elledge, RM, Green, S, Howes, L,  et al. 1997bcl-2, p53, and response to tamoxifen in estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group studyJ Clin Oncol1519161922PubMedGoogle Scholar
  18. 18.
    Bergh, J, Norberg, T, Sjogren, S,  et al. 1995Complete sequencing of the p53 gene provides prognostic information in breast cancer patients, particularly in relation to adjuvant systemic therapy and radiotherapyNat Med110291034PubMedCrossRefGoogle Scholar
  19. 19.
    Silvestrini, R, Benini, E, Veneroni, S,  et al. 1996p53 and bcl-2 expression correlates with clinical outcome in a series of node-positive breast cancer patientsJ Clin Oncol1416041610PubMedGoogle Scholar
  20. 20.
    Berns, EM, Klijn, JG, Look, MP,  et al. 2003Combined vascular endothelial growth factor and TP53 status predicts poor response to tamoxifen therapy in estrogen receptor-positive advanced breast cancerClin Cancer Res912531258PubMedGoogle Scholar
  21. 21.
    Berns, EM, Klijn, JG, van Putten, WL,  et al. 1998p53 protein accumulation predicts poor response to tamoxifen therapy of patients with recurrent breast cancerJ Clin Oncol16121127PubMedGoogle Scholar
  22. 22.
    Horne, GM, Anderson, JJ, Tiniakos, DG,  et al. 1996p53 protein as a prognostic indicator in breast carcinoma: a comparison of four antibodies for immunohistochemistryBr J Cancer732935PubMedGoogle Scholar

Copyright information

© The Japan Society of Clinical Oncology 2006

Authors and Affiliations

  • Kazuharu Kai
    • 1
    • 2
  • Reiki Nishimura
    • 2
  • Nobuyuki Arima
    • 3
  • Haruhiko Miyayama
    • 3
  • Hirotaka Iwase
    • 1
  1. 1.Breast and Endocrine Surgery, Faculty of Medical and Pharmaceutical ScienceKumamoto UniversityKumamotoJapan
  2. 2.Breast and Endocrine SurgeryKumamoto City HospitalKumamotoJapan
  3. 3.Clinical PathologyKumamoto City HospitalKumamotoJapan

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