Biological activity of anastrozole in postmenopausal patients with advanced breast cancer

Effects on estrogens and bone metabolism

E. Bombardieri, E. Bajetta, A. Martinetti, N. Zilembo, P. Pozzi, I. La Torre, L. Ferrari, E. Seregni, R. Longarini, G. Salvucci

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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 (E 1, E 2 and E 1-S), androgens [androstenedione (Δ 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 E 1 and E 1-S levels decreased on average by 56% (range 23.1-88.8%) and 75.8% (range 52.4-87.2%), respectively; E 2 decreased on average by 62% (range 31.4-89.6%). No significant changes were detected in levels of androgens of 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.

Original languageEnglish
Pages (from-to)1059-1066
Number of pages8
JournalAnnals of Oncology
Volume13
Issue number7
DOIs
Publication statusPublished - 2002

Fingerprint

Estrogens
Breast Neoplasms
Bone and Bones
Sex Hormone-Binding Globulin
Androgens
Serum
Gonadotropins
Alkaline Phosphatase
Bone Resorption
Testosterone
17-alpha-Hydroxyprogesterone
Dehydroepiandrosterone Sulfate
Aromatase Inhibitors
Dehydroepiandrosterone
Androstenedione
Dihydrotestosterone
Bone Diseases
Osteocalcin
Follicle Stimulating Hormone
Luteinizing Hormone

Keywords

  • Androgens
  • Aromatase inhibitors
  • Bone metabolism markers
  • Breast cancer
  • Estrogens

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Biological activity of anastrozole in postmenopausal patients with advanced breast cancer : Effects on estrogens and bone metabolism. / Bombardieri, E.; Bajetta, E.; Martinetti, A.; Zilembo, N.; Pozzi, P.; La Torre, I.; Ferrari, L.; Seregni, E.; Longarini, R.; Salvucci, G.

In: Annals of Oncology, Vol. 13, No. 7, 2002, p. 1059-1066.

Research output: Contribution to journalArticle

Bombardieri, E. ; Bajetta, E. ; Martinetti, A. ; Zilembo, N. ; Pozzi, P. ; La Torre, I. ; Ferrari, L. ; Seregni, E. ; Longarini, R. ; Salvucci, G. / Biological activity of anastrozole in postmenopausal patients with advanced breast cancer : Effects on estrogens and bone metabolism. In: Annals of Oncology. 2002 ; Vol. 13, No. 7. pp. 1059-1066.
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title = "Biological activity of anastrozole in postmenopausal patients with advanced breast cancer: Effects on estrogens and bone metabolism",
abstract = "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 (E 1, E 2 and E 1-S), androgens [androstenedione (Δ 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 E 1 and E 1-S levels decreased on average by 56{\%} (range 23.1-88.8{\%}) and 75.8{\%} (range 52.4-87.2{\%}), respectively; E 2 decreased on average by 62{\%} (range 31.4-89.6{\%}). No significant changes were detected in levels of androgens of 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.",
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T1 - Biological activity of anastrozole in postmenopausal patients with advanced breast cancer

T2 - Effects on estrogens and bone metabolism

AU - Bombardieri, E.

AU - Bajetta, E.

AU - Martinetti, A.

AU - Zilembo, N.

AU - Pozzi, P.

AU - La Torre, I.

AU - Ferrari, L.

AU - Seregni, E.

AU - Longarini, R.

AU - Salvucci, G.

PY - 2002

Y1 - 2002

N2 - 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 (E 1, E 2 and E 1-S), androgens [androstenedione (Δ 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 E 1 and E 1-S levels decreased on average by 56% (range 23.1-88.8%) and 75.8% (range 52.4-87.2%), respectively; E 2 decreased on average by 62% (range 31.4-89.6%). No significant changes were detected in levels of androgens of 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.

AB - 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 (E 1, E 2 and E 1-S), androgens [androstenedione (Δ 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 E 1 and E 1-S levels decreased on average by 56% (range 23.1-88.8%) and 75.8% (range 52.4-87.2%), respectively; E 2 decreased on average by 62% (range 31.4-89.6%). No significant changes were detected in levels of androgens of 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.

KW - Androgens

KW - Aromatase inhibitors

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KW - Breast cancer

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