Annals of Oncology 13:1059-1066, 2002
© 2002 European Society for Medical Oncology
Original Paper |
Biological activity of anastrozole in postmenopausal patients with advanced breast cancer: effects on estrogens and bone metabolism
1 Medical Oncology Unit B and 2 Nuclear Medicine Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
Received 12 July 2001; revised 17 September 2001; accepted 2 October 2001
Background:
To study the short-term biological effect of anastrozole on serum estrogens, androgens, 17-hydroxyprogesterone (17OH-PGR), gonadotrophins, sex hormone binding globulin (SHBG) and bone metabolism markers.
Materials and methods:
Thirty-four consecutive patients with advanced breast cancer received anastrozole 1 mg/day. Blood samples were taken before commencement of treatment and at 2, 4, 8 and 12 weeks during treatment to measure serum levels of estrogens (E1, E2 and E1-S), androgens [androstenedione (
4), dihydrotestosterone (DHT), testosterone (TST), free TST, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S)], 17OH-PGR, SHBG and gonadotrophins. As an indicator of bone resorption, we measured serum levels of C-terminal telopeptide of type I collagen (ICTP) and the cross-linked N-telopeptide of type I collagen (NTx), and for osteoblastic activity, intact osteocalcin (BGP) and bone alkaline phosphatase (BAP).
Results:
After 2 weeks E1 and E1-S levels decreased on average by 56% (range 23.1–88.8%) and 75.8% (range 52.4–87.2%), respectively; E2 decreased on average by 62% (range 31.4–89.6%). No significant changes were detected in levels of androgens or 17OH-PGR. There was a significant increase in gonadotrophins over time (P = 0.0001 for both luteinizing hormone and follicle-stimulating hormone), and a significant decrease in SHBG (P = 0.0001). A progressive significant increase in bone metabolism serum markers was detected in all patients: BAP, P = 0.039; BGP, P = 0.016; ICTP, P = 0.0021; and NTx, P = 0.0013. In particular, patients with bone metastases had a statistically significant increase of bone resorption markers (ICTP, P = 0.0019; NTx, P = 0.025) and borderline for bone formation markers. In patients without bone disease, BAP, BGP and ICTP remained unchanged, whereas serum NTx significantly increased (P = 0.019).
Conclusions:
Anastrozole is a selective aromatase inhibitor as it does not modify serum levels of androgens and 17OH-PGR. In our experience no relationship was found in the short-term period between serum estrogen suppression and bone metabolism.
Key words: androgens, aromatase inhibitors, bone metabolism markers, breast cancer, estrogens
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