Effects of the aromatase inhibitor letrozole on normal breast epithelial cell proliferation and metabolic indices in postmenopausal women: a pilot study for breast cancer prevention.
Cancer Epidemiol Biomarkers Prev
; 11(7): 614-21, 2002 Jul.
Article
en En
| MEDLINE
| ID: mdl-12101108
ABSTRACT
The aromatase enzyme converts androgens to estrogens and is the therapeutic target for aromatase inhibitors in postmenopausal patients with estrogen receptor-positive metastatic breast cancer. Third-generation inhibitors such as letrozole are being considered as potential prophylactic agents for breast cancer. The rationale for their preventive application would be aided by knowledge of their effects on the normal breast and on other estrogen-dependent processes such as bone and lipid metabolism. Thirty-two women without active breast disease were recruited to 3-month treatment with letrozole (2.5 mg/day). Core-cut biopsies from the breast and blood samples were collected before and at the end of treatment. Plasma estradiol levels were markedly suppressed in all but two patients, who were excluded from the efficacy assessment. There was no significant change in the proliferation marker Ki67 (mean change, -23%; 95% confidence interval, -50% to +23%) or estrogen receptor in breast epithelial cells with treatment. Similarly, there were no significant changes in plasma levels of insulin-like growth factor I or lipid profiles. However, there was a significant increase (25%) in the levels of the bone resorption marker C-telopeptide crosslinks (CTx). We conclude that any prophylactic effect of letrozole is not likely to be dependent on antiproliferative effects on normal breast. Studies in healthy patients will need to recognize the potential for enhanced bone resorption.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Triazoles
/
Enfermedades de la Mama
/
Receptores de Estrógenos
/
Antígeno Ki-67
/
Inhibidores Enzimáticos
/
Células Epiteliales
/
Nitrilos
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
Límite:
Aged
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Cancer Epidemiol Biomarkers Prev
Asunto de la revista:
BIOQUIMICA
/
EPIDEMIOLOGIA
/
NEOPLASIAS
Año:
2002
Tipo del documento:
Article
País de afiliación:
Reino Unido