Estrogen-metabolizing enzymes in breast cancers from women over the age of 80 years

J Clin Endocrinol Metab. 2006 Feb;91(2):607-13. doi: 10.1210/jc.2005-1967. Epub 2005 Nov 22.

Abstract

Context: Aromatase, steroid sulfatase, and 17beta-hydroxysteroid dehydrogenase type 1 (HSD-1) peripherally up-regulate, whereas estrogen sulfotransferase (EST) and HSD-2 down-regulate, the synthesis of active and more potent estrogens. These estrogen-metabolizing enzymes (EMEs) are important in postmenopausal breast cancers, but have never been systematically examined in breast cancers of the elderly.

Objective and design: mRNA levels of EMEs in cancerous and normal breast tissues from 39 elderly patients (age, 80-99 yr) were compared with those from 39 controls (age, 37-70 yr) or compared according to estrogen (ER)/progesterone (PR) receptor status.

Results: Aromatase levels were higher in cancers of the elderly (EldCa) than in normal tissue of the elderly (P = 0.0008) or cancers of controls (P = 0.0033). In contrast, levels of steroid sulfatase and EST were higher in cancers of controls than normal tissue of controls (P = 0.0046 and P < 0.0001, respectively) or EldCa (P = 0.0001 and P < 0.0001, respectively). Levels of HSD-1 and HSD-2 did not differ significantly between any two of the categories. Among EldCa, HSD-1 levels were higher in ER/PR-positive than in ER/PR-negative carcinomas, whereas EST and HSD-2 exhibited opposite results.

Conclusions: The importance of aromatase is relatively increased in EldCa. ER/PR-positive EldCa exhibited a pattern of EMEs more beneficial to the production of estrogen than did ER/PR-negative EldCa. The specific pattern exhibited in EldCa may elucidate the role of EMEs in the absence of ovarian estrogens in the pathogenesis of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Mucinous / enzymology
  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Aromatase / genetics
  • Aromatase / metabolism*
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Carcinoma, Ductal, Breast / enzymology
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Lobular / enzymology
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / metabolism
  • Estrogens / biosynthesis*
  • Female
  • Humans
  • Hydroxysteroid Dehydrogenases / genetics
  • Hydroxysteroid Dehydrogenases / metabolism*
  • Immunohistochemistry
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Steryl-Sulfatase / genetics
  • Steryl-Sulfatase / metabolism*
  • Sulfotransferases / genetics
  • Sulfotransferases / metabolism*

Substances

  • Estrogens
  • RNA, Messenger
  • Hydroxysteroid Dehydrogenases
  • Aromatase
  • Sulfotransferases
  • estrone sulfotransferase
  • Steryl-Sulfatase