The luteinising hormone-releasing hormone analogue triptorelin with or without the aromatase inhibitor formestane in premenopausal breast cancer: Effects on bone metabolism markers

Antonia Martinetti, Leonardo Ferrari, Luigi Celio, Luigi Mariani, Rosalba Miceli, Nicoletta Zilembo, Maria Di Bartolomeo, Luisa Toffolatti, Paola Pozzi, Ettore Seregni, Emilio Bombardieri, Emilio Bajetta

Research output: Contribution to journalArticle

Abstract

Background: the combination of a luteinising hormone-releasing hormone (LH-RH) analogue and an aromatase inhibitor (AI) induces greater oestrogen suppression than the analogue alone in premenopausal breast cancer. However, very few data on the biological effects of such a combination are currently available. Aim of the study: the short-term effects of treatment with the LH-RH analogue triptorelin alone or in association with the AI formestane on bone metabolism were investigated in premenopausal breast cancer. Circulating levels of the bone formation markers carboxy-terminal and amino-terminal propeptides of type I procollagen (PICP and PINP) and the bone resorption marker cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were assessed. In addition, serum levels of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and interleukin 6 (IL-6) were evaluated. Patients and methods: twenty-one patients with advanced breast cancer were randomly given triptorelin monthly alone (n = 10, arm A) or in combination with formestane fortnightly (n = 11, arm B). Blood samples were collected over a 3-month period. Results: serum PICP and PINP levels increased significantly over time (P = 0.0065 and 0.0197 in arm A and B, respectively); no change in ICTP levels was observed. A rise in IGF-I and IGFBP-3 levels was seen in each treatment group, but only the increase in IGF-I was significant (P = 0.0138, always). The on-treatment levels of the bone turnover markers and IGF-system components were inversely correlated with serum oestrogens. Neither treatment modalities significantly affected serum IL-6 levels over time. No difference in the behaviour of any of the assessed biomarkers was observed between patients with or without skeletal metastases. Conclusion: it is worth noting that complete oestrogen depletion, at least in our case series, seems to increase only osteoblastic activity markers. The observed modifications appear to be related to oestrogen depletion per se rather than the degree of oestrogen suppression or the different therapeutic regimen administered.

Original languageEnglish
Pages (from-to)65-73
Number of pages9
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume75
Issue number1
DOIs
Publication statusPublished - Dec 1 2000

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Triptorelin Pamoate
Aromatase Inhibitors
Metabolism
Gonadotropin-Releasing Hormone
Bone
Estrogens
Breast Neoplasms
Bone and Bones
Insulin-Like Growth Factor I
Insulin-Like Growth Factor Binding Protein 3
Collagen Type I
Serum
Interleukin-6
Insulin-Like Growth Factor Binding Protein 6
Estradiol Congeners
Therapeutics
Insulin-Like Growth Factor Binding Proteins
Bone Remodeling
Biomarkers
Somatomedins

Keywords

  • Aromatase inhibitors
  • Bone metabolism markers
  • Breast cancer
  • Cytokines
  • Gonadotrophin releasing-hormone
  • Growth factors
  • Oestrogens

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

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title = "The luteinising hormone-releasing hormone analogue triptorelin with or without the aromatase inhibitor formestane in premenopausal breast cancer: Effects on bone metabolism markers",
abstract = "Background: the combination of a luteinising hormone-releasing hormone (LH-RH) analogue and an aromatase inhibitor (AI) induces greater oestrogen suppression than the analogue alone in premenopausal breast cancer. However, very few data on the biological effects of such a combination are currently available. Aim of the study: the short-term effects of treatment with the LH-RH analogue triptorelin alone or in association with the AI formestane on bone metabolism were investigated in premenopausal breast cancer. Circulating levels of the bone formation markers carboxy-terminal and amino-terminal propeptides of type I procollagen (PICP and PINP) and the bone resorption marker cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were assessed. In addition, serum levels of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and interleukin 6 (IL-6) were evaluated. Patients and methods: twenty-one patients with advanced breast cancer were randomly given triptorelin monthly alone (n = 10, arm A) or in combination with formestane fortnightly (n = 11, arm B). Blood samples were collected over a 3-month period. Results: serum PICP and PINP levels increased significantly over time (P = 0.0065 and 0.0197 in arm A and B, respectively); no change in ICTP levels was observed. A rise in IGF-I and IGFBP-3 levels was seen in each treatment group, but only the increase in IGF-I was significant (P = 0.0138, always). The on-treatment levels of the bone turnover markers and IGF-system components were inversely correlated with serum oestrogens. Neither treatment modalities significantly affected serum IL-6 levels over time. No difference in the behaviour of any of the assessed biomarkers was observed between patients with or without skeletal metastases. Conclusion: it is worth noting that complete oestrogen depletion, at least in our case series, seems to increase only osteoblastic activity markers. The observed modifications appear to be related to oestrogen depletion per se rather than the degree of oestrogen suppression or the different therapeutic regimen administered.",
keywords = "Aromatase inhibitors, Bone metabolism markers, Breast cancer, Cytokines, Gonadotrophin releasing-hormone, Growth factors, Oestrogens",
author = "Antonia Martinetti and Leonardo Ferrari and Luigi Celio and Luigi Mariani and Rosalba Miceli and Nicoletta Zilembo and {Di Bartolomeo}, Maria and Luisa Toffolatti and Paola Pozzi and Ettore Seregni and Emilio Bombardieri and Emilio Bajetta",
year = "2000",
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doi = "10.1016/S0960-0760(00)00138-2",
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TY - JOUR

T1 - The luteinising hormone-releasing hormone analogue triptorelin with or without the aromatase inhibitor formestane in premenopausal breast cancer

T2 - Effects on bone metabolism markers

AU - Martinetti, Antonia

AU - Ferrari, Leonardo

AU - Celio, Luigi

AU - Mariani, Luigi

AU - Miceli, Rosalba

AU - Zilembo, Nicoletta

AU - Di Bartolomeo, Maria

AU - Toffolatti, Luisa

AU - Pozzi, Paola

AU - Seregni, Ettore

AU - Bombardieri, Emilio

AU - Bajetta, Emilio

PY - 2000/12/1

Y1 - 2000/12/1

N2 - Background: the combination of a luteinising hormone-releasing hormone (LH-RH) analogue and an aromatase inhibitor (AI) induces greater oestrogen suppression than the analogue alone in premenopausal breast cancer. However, very few data on the biological effects of such a combination are currently available. Aim of the study: the short-term effects of treatment with the LH-RH analogue triptorelin alone or in association with the AI formestane on bone metabolism were investigated in premenopausal breast cancer. Circulating levels of the bone formation markers carboxy-terminal and amino-terminal propeptides of type I procollagen (PICP and PINP) and the bone resorption marker cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were assessed. In addition, serum levels of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and interleukin 6 (IL-6) were evaluated. Patients and methods: twenty-one patients with advanced breast cancer were randomly given triptorelin monthly alone (n = 10, arm A) or in combination with formestane fortnightly (n = 11, arm B). Blood samples were collected over a 3-month period. Results: serum PICP and PINP levels increased significantly over time (P = 0.0065 and 0.0197 in arm A and B, respectively); no change in ICTP levels was observed. A rise in IGF-I and IGFBP-3 levels was seen in each treatment group, but only the increase in IGF-I was significant (P = 0.0138, always). The on-treatment levels of the bone turnover markers and IGF-system components were inversely correlated with serum oestrogens. Neither treatment modalities significantly affected serum IL-6 levels over time. No difference in the behaviour of any of the assessed biomarkers was observed between patients with or without skeletal metastases. Conclusion: it is worth noting that complete oestrogen depletion, at least in our case series, seems to increase only osteoblastic activity markers. The observed modifications appear to be related to oestrogen depletion per se rather than the degree of oestrogen suppression or the different therapeutic regimen administered.

AB - Background: the combination of a luteinising hormone-releasing hormone (LH-RH) analogue and an aromatase inhibitor (AI) induces greater oestrogen suppression than the analogue alone in premenopausal breast cancer. However, very few data on the biological effects of such a combination are currently available. Aim of the study: the short-term effects of treatment with the LH-RH analogue triptorelin alone or in association with the AI formestane on bone metabolism were investigated in premenopausal breast cancer. Circulating levels of the bone formation markers carboxy-terminal and amino-terminal propeptides of type I procollagen (PICP and PINP) and the bone resorption marker cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were assessed. In addition, serum levels of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and interleukin 6 (IL-6) were evaluated. Patients and methods: twenty-one patients with advanced breast cancer were randomly given triptorelin monthly alone (n = 10, arm A) or in combination with formestane fortnightly (n = 11, arm B). Blood samples were collected over a 3-month period. Results: serum PICP and PINP levels increased significantly over time (P = 0.0065 and 0.0197 in arm A and B, respectively); no change in ICTP levels was observed. A rise in IGF-I and IGFBP-3 levels was seen in each treatment group, but only the increase in IGF-I was significant (P = 0.0138, always). The on-treatment levels of the bone turnover markers and IGF-system components were inversely correlated with serum oestrogens. Neither treatment modalities significantly affected serum IL-6 levels over time. No difference in the behaviour of any of the assessed biomarkers was observed between patients with or without skeletal metastases. Conclusion: it is worth noting that complete oestrogen depletion, at least in our case series, seems to increase only osteoblastic activity markers. The observed modifications appear to be related to oestrogen depletion per se rather than the degree of oestrogen suppression or the different therapeutic regimen administered.

KW - Aromatase inhibitors

KW - Bone metabolism markers

KW - Breast cancer

KW - Cytokines

KW - Gonadotrophin releasing-hormone

KW - Growth factors

KW - Oestrogens

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DO - 10.1016/S0960-0760(00)00138-2

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JO - Journal of Steroid Biochemistry and Molecular Biology

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