title: Efficacy of high-dose toremifene therapy in postmenopausal patients with metastatic breast cancer resistant to aromatase inhibitors:a retrospective, single-institution study.
abstract: BACKGROUND
  Aromatase inhibitors(AI)have established efficacy as first-line therapy in postmenopausal patients with hormone-sensitive metastatic breast cancer(MBC). However,the use of endocrine therapy has not yet been established for second-line and later therapy. Our study examined the efficacy of high-dose toremifene therapy(HD-TOR)in patients with MBC resistant to AIs.
  
  
  METHODS
  A retrospective analysis was carried out to determine outcomes in 85 postmenopausal patients with MBC resistant to AIs who began HD-TOR between May 2001 and October 2011. The patients received toremifene 120 mg once daily on consecutive days.
  
  
  RESULTS
  The objective response rate(ORR)was 21.2%,the clinical benefit rate(CBR)was 41.2%,and the median time to treatment failure(TTF)was 7.3 months. The CBR was high in patients with ER-positive status(p=0.045),no visceral metastasis(p=0.037),HD -TOR as first- or second-line therapy(p=0.007),no history of tamoxifen(TAM)therapy(p=0.019),and no history of chemotherapy(p=0.017). Multivariate analysis showed that ER-positive status(p=0.005, odds ratio: 0.064)and no visceral metastasis(p=0.034, odds ratio: 0.323)were independent predictors of efficacy. The TTF was significantly longer in patients with ER-positive status(p=0.019)and no history of TAM therapy(p=0.015). Multivariate analysis showed that ER-positive status(p=0.025, hazard ratio: 0.377)and no history of TAM therapy(p=0.002, hazard ratio: 0.422)were independent predictors of efficacy. No patient discontinued HDTOR therapy due to adverse events.
  
  
  CONCLUSIONS
  HD-TOR is an effective endocrine therapy for patients with MBC who have failed AIs.
authors.affiliation: Breast Center, Dokkyo Medical University Koshigaya Hospital.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ishizuna
authors.forename: Jun
authors.initials: J
authors.lastname: Ninomiya
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Ogawa
authors.forename: Eiichi
authors.initials: E
authors.lastname: Tsuji
authors.forename: Makoto
authors.initials: M
authors.lastname: Kojima
authors.forename: Miho
authors.initials: M
authors.lastname: Kawashima
authors.forename: Miwako
authors.initials: M
authors.lastname: Nozaki
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Yamagishi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ueda
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Oya
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017698:Postmenopause; D012189:Retrospective Studies; D017312:Toremifene / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D017312:Toremifene