title: p53 protein accumulation predicts resistance to endocrine therapy and decreased post-relapse survival in metastatic breast cancer.
abstract: BACKGROUND
  Endocrine therapy is the most important treatment option for women with hormone receptor-positive breast cancer. The potential mechanisms for endocrine resistance involve estrogen receptor (ER)-coregulatory proteins and cross-talk between ER and other growth factor-signaling networks. However, the factors and pathways responsible for endocrine resistance are still poorly identified.
  
  
  METHODS
  The expression of HER2, p53, and Ki67 was examined by immunohistochemistry in primary breast tumour specimens from 73 metastatic breast cancer patients who received first-line treatment with endocrine therapy on relapse, and analysed to determine whether expression of these molecular markers affected the response to endocrine therapy.
  
  
  RESULTS
  Of the 73 invasive ductal carcinomas, 12.3%, 21.9%, and 35.6% were positive for HER2 overexpression, p53 protein accumulation, and Ki67 expression, respectively. All patients received endocrine therapy as first-line treatment for metastatic breast cancer; 34 patients (46.6%) responded. Patients with primary breast tumours that had p53 protein accumulation and Ki67 expression showed significantly more resistance to endocrine therapy (P = 0.0049 and P = 0.024, respectively). There were also tendencies for HER2 overexpression to correlate with resistance to endocrine therapy, but this did not reach significance. p53 protein accumulation and HER2 overexpression significantly reduced post-relapse survival (P < 0.0001 and P = 0.001, respectively), and these factors were also statistically significant in a multivariate analysis.
  
  
  CONCLUSIONS
  These data suggest that p53 protein accumulation is helpful in selecting patients who may benefit from endocrine therapy and is a prognostic marker in hormone receptor-positive metastatic breast cancer.
authors.affiliation: Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-ku, Nagoya 467-8601, Japan. hirokoy@med.nagoya-cu.ac.jp
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yamashita
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Toyama
authors.forename: Mariko
authors.initials: M
authors.lastname: Nishio
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ando
authors.forename: Maho
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: Zhenhuan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Shunzo
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujii
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Iwase
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000401:mortality / Q000503:physiopathology* / Q000556:secondary / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000401:mortality / Q000503:physiopathology* / Q000556:secondary / Q000628:therapy; D019008:Drug Resistance, Neoplasm; D005260:Female; D018734:Genes, erbB-2 / Q000502:physiology; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53