title: p53 expression status is a significant molecular marker in predicting the time to endocrine therapy failure in recurrent breast cancer: a cohort study.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Breast and Endocrine Surgery, Faculty of Medical and Pharmaceutical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan. 20105995@fc.kuh.kumamoto-u.ac.jp
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Kai
authors.forename: Reiki
authors.initials: R
authors.lastname: Nishimura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Arima
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Miyayama
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Iwase
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012983:Soft Tissue Neoplasms / Q000378:metabolism / Q000556:secondary; D015996:Survival Rate; D013997:Time Factors; D017211:Treatment Failure; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D020847:Estrogen Receptor Modulators; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53