Concentrations of oestrone and 4-hydroxyandrostenedione in malignant and normal breast tissues

Int J Cancer. 1991 Oct 21;49(4):562-5. doi: 10.1002/ijc.2910490415.


4-Hydroxyandrostenedione (4-OHA) is a specific inhibitor of aromatase activity used for the treatment of breast cancer in post-menopausal women. Treatment with 4-OHA has been shown to inhibit the peripheral conversion of androstenedione to oestrone and reduce plasma oestrogen concentrations, but the effect of treatment on breast-tissue oestrone concentrations is not known. We have therefore examined the effect of treatment with 4-OHA on oestrone concentrations in normal and malignant breast tissues and also measured plasma and tissue 4-OHA concentrations. Changes in tumour oestrone concentrations were related to DNA polymerase alpha activity, a marker of cellular proliferation. Blood and breast-tissue samples were obtained before and 36 hr after treatment with 4-OHA. The mean plasma concentration of 4-OHA was 27.9 +/- 19.3 ng/ml, compared with levels of 33.7 +/- 25.6 ng/g for breast tumour and 13.5 +/- 11.5 ng/g for normal breast tissue. There was a significant correlation between 4-OHA concentrations in plasma and normal breast tissue (r = 0.91, p less than 0.001). Treatment with 4-OHA resulted in a significant (p less than 0.02) decrease in breast-tissue oestrone concentrations. For 3/4 tumour samples, a marked decrease in the concentration of oestrone (78 +/- 4%) was associated with a similar decrease (64 +/- 16%) in DNA polymerase alpha activity. It is concluded that treatment with 4-OHA effectively reduces breast-tissue exposure to oestrogen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Androstenedione / analogs & derivatives*
  • Androstenedione / analysis
  • Androstenedione / blood
  • Androstenedione / therapeutic use
  • Aromatase Inhibitors
  • Breast / chemistry*
  • Breast / pathology
  • Breast Neoplasms / blood
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • DNA Polymerase II / analysis
  • Estrone / analysis*
  • Estrone / blood
  • Female
  • Humans
  • Neoplasm Staging


  • Aromatase Inhibitors
  • Estrone
  • Androstenedione
  • DNA Polymerase II
  • formestane