title: Intratumoral concentration of estrogens and clinicopathological changes in ductal carcinoma in situ following aromatase inhibitor letrozole treatment.
abstract: BACKGROUND
  Estrogens have important roles in ductal carcinoma in situ (DCIS) of the breast. However, the significance of presurgical aromatase inhibitor treatment remains unclear. Therefore, we examined intratumoral concentration of estrogens and changes of clinicopathological factors in DCIS after letrozole treatment.
  
  
  METHODS
  Ten cases of postmenopausal oestrogen receptor (ER)-positive DCIS were examined. They received oral letrozole before the surgery, and the tumour size was evaluated by ultrasonography. Surgical specimens and corresponding biopsy samples were used for immunohistochemistry. Snap-frozen specimens were also available in a subset of cases, and used for hormone assays and microarray analysis.
  
  
  RESULTS
  Intratumoral oestrogen levels were significantly lower in DCIS treated with letrozole compared with that in those without the therapy. A great majority of oestrogen-induced genes showed low expression levels in DCIS treated with letrozole by microarray analysis. Moreover, letrozole treatment reduced the greatest dimension of DCIS, and significantly decreased Ki-67 and progesterone receptor immunoreactivity in DCIS tissues.
  
  
  CONCLUSIONS
  These results suggest that estrogens are mainly produced by aromatase in DCIS tissues, and aromatase inhibitors potently inhibit oestrogen actions in postmenopausal ER-positive DCIS through rapid deprivation of intratumoral estrogens.
authors.affiliation: Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, 980-8575 Sendai, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takagi
authors.forename: T
authors.initials: T
authors.lastname: Ishida
authors.forename: Y
authors.initials: Y
authors.lastname: Miki
authors.forename: H
authors.initials: H
authors.lastname: Hirakawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kakugawa
authors.forename: G
authors.initials: G
authors.lastname: Amano
authors.forename: A
authors.initials: A
authors.lastname: Ebata
authors.forename: N
authors.initials: N
authors.lastname: Mori
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Amari
authors.forename: N
authors.initials: N
authors.lastname: Ohuchi
authors.forename: H
authors.initials: H
authors.lastname: Sasano
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000368:Aged; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D047072:Aromatase Inhibitors; D004967:Estrogens; D019394:Ki-67 Antigen; D009570:Nitriles; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles; D000077289:Letrozole; D001141:Aromatase