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Anastrozole (‘Arimidex’) blocks oestrogen synthesis both peripherally and within the breast in postmenopausal women with large operable breast cancer
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Anastrozole (‘Arimidex’) blocks oestrogen synthesis both peripherally and within the breast in postmenopausal women with large operable breast cancer
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Journal Article
Anastrozole (‘Arimidex’) blocks oestrogen synthesis both peripherally and within the breast in postmenopausal women with large operable breast cancer
2002
Overview
The effect of anastrozole on peripheral and tumour aromatase activity and oestrogen levels in postmenopausal patients with oestrogen receptor-rich breast tumours was investigated. Twenty-six patients were randomly allocated to treatment with anastrozole 1 mg (
n
=13) or 10 mg (
n
=13), once daily. Before and after 12 weeks' treatment, patients were infused with
3
H-Δ
4
androstenedione (20 MBq) and
14
C-oestrone (E
1
) (1 MBq) for 18 h. Oestrogens were purified from excised tumours and plasma samples taken after each infusion. Peripheral and tumour aromatase activity and tumour E
1
uptake were calculated from levels of
3
H and
14
C in purified E
1
fractions from tumour and plasma. Endogenous tumour oestrogens were measured by radioimmunoassay. Twenty-three patients were available for analysis (1 mg group,
n
=12; 10 mg group,
n
=11). Following treatment, anastrozole (1 and 10 mg) markedly inhibited peripheral aromatase in all patients (the difference between pre- and on-treatment values being highly significant
P
<0.0001).
In situ
aromatase activity was also profoundly decreased by anastrozole treatment in 16 of 19 tumours (the difference with treatment also being highly significant
P
=0.0009). Most tumours were able to concentrate E
1
beyond levels in the circulation; anastrozole treatment had no consistent effect on uptake of E
1
. Endogenous tumour levels of both E
1
and oestradiol (E
2
) were significantly reduced with therapy (
P
=0.028 for E
1
and
P
=0.0019 for E
2
). Anastrozole (1 and 10 mg daily) effectively suppresses aromatase activity, and subsequently oestrogen levels, within the breast tissue of postmenopausal women with large or locally advanced, operable, oestrogen receptor-rich breast cancers.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Androstenedione - administration & dosage
/ Antineoplastic Agents, Hormonal - therapeutic use
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Breast Neoplasms - drug therapy
/ Breast Neoplasms - enzymology
/ Clinical
/ Enzyme Inhibitors - therapeutic use
/ Estrogen Antagonists - therapeutic use
/ Estrone - administration & dosage
/ Female
/ Humans
/ Neoplasms, Hormone-Dependent - drug therapy
/ Neoplasms, Hormone-Dependent - enzymology
/ Oncology
/ Pharmacology. Drug treatments
