Premenopausal breast cancer patients treated with a gonadotropin-releasing hormone analog alone or in combination with an aromatase inhibitor: A comparative endocrine study

Luigi Celio, Antonia Martinetti, Leonardo Ferrari, Roberto Buzzoni, Luigi Mariani, Rosalba Miceli, Ettore Seregni, Giuseppe Procopio, Antonio Cassata, Emilio Bombardieri, Emilio Bajetta

Research output: Contribution to journalArticle

Abstract

Background: The combination of a GnRH analogue and an aromatase inhibitor can induce a complete estrogen blockade in premenopausal breast cancer patients. Material and Methods: Twenty-one premenopausal women with advanced breast cancer were randomised to receive the GnRH analog triptorelin (3.75 mg im monthly; n = 10) alone or in combination with the aromatase inhibitor formestane (4-OHA, 500 mg im fortnightly; n = 11) to compare the effect of both treatments on the patients' estrogenic milieu. Therefore, serum estrogen, gonadotropin and sex hormone-binding globulin (SHBG) levels were investigated before the start of treatment and subsequently over a three-month period. Results: There was a significant between-group difference in estrogen suppression during therapy. In comparison with baseline values, after four weeks of treatment the estradiol levels decreased by an average of 86.9% (95% CI, 70.5-94.2%) in the group treated with triptorelin alone and by 97.3% (95% CI, 94.1-98.8%; P = 0.0422) in the combination group; the respective figures for estrone were 48.5% (95% CI, 27.5-63.5%) and 70.4% (95% CI, 52.3-81.6%; P = 0.0007) and for estrone sulfate 56.7% (95% CI, 40-68.8%) and 80.5% (95% CI, 69.4-87.6%; P = 0.0055). No difference was observed between the groups in terms of gonadotropin suppression; both treatment modalities led to a slight but delayed decrease in SHBG levels. Three of the patients treated with triptorelin alone experienced tumor regression compared with four patients in the combination group. No appreciable side effects of the combination therapy were observed. Conclusion: The treatment of premenopausal patients with triptorelin plus 4-OHA is feasible and leads to a much greater inhibition of main circulating estrogens than treatment with the analog alone. Since the combination of a GnRH analog and an aromatase inhibitor might potentially enhance the anti-tumor efficacy of the analog alone owing to more favorable endocrine effects, such a therapeutic approach deserves more extensive evaluation in the clinical setting.

Original languageEnglish
Pages (from-to)2261-2268
Number of pages8
JournalAnticancer Research
Volume19
Issue number3 B
Publication statusPublished - 1999

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Aromatase Inhibitors
Gonadotropin-Releasing Hormone
Breast Neoplasms
Triptorelin Pamoate
Estrogens
Sex Hormone-Binding Globulin
Therapeutics
Gonadotropins
Estrone
Estradiol
Neoplasms

Keywords

  • Aromatase inhibition
  • Formestane
  • GnRH analog
  • Premenopausal breast cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{dfbdd80659de4eb8812f0a1a68fa54a4,
title = "Premenopausal breast cancer patients treated with a gonadotropin-releasing hormone analog alone or in combination with an aromatase inhibitor: A comparative endocrine study",
abstract = "Background: The combination of a GnRH analogue and an aromatase inhibitor can induce a complete estrogen blockade in premenopausal breast cancer patients. Material and Methods: Twenty-one premenopausal women with advanced breast cancer were randomised to receive the GnRH analog triptorelin (3.75 mg im monthly; n = 10) alone or in combination with the aromatase inhibitor formestane (4-OHA, 500 mg im fortnightly; n = 11) to compare the effect of both treatments on the patients' estrogenic milieu. Therefore, serum estrogen, gonadotropin and sex hormone-binding globulin (SHBG) levels were investigated before the start of treatment and subsequently over a three-month period. Results: There was a significant between-group difference in estrogen suppression during therapy. In comparison with baseline values, after four weeks of treatment the estradiol levels decreased by an average of 86.9{\%} (95{\%} CI, 70.5-94.2{\%}) in the group treated with triptorelin alone and by 97.3{\%} (95{\%} CI, 94.1-98.8{\%}; P = 0.0422) in the combination group; the respective figures for estrone were 48.5{\%} (95{\%} CI, 27.5-63.5{\%}) and 70.4{\%} (95{\%} CI, 52.3-81.6{\%}; P = 0.0007) and for estrone sulfate 56.7{\%} (95{\%} CI, 40-68.8{\%}) and 80.5{\%} (95{\%} CI, 69.4-87.6{\%}; P = 0.0055). No difference was observed between the groups in terms of gonadotropin suppression; both treatment modalities led to a slight but delayed decrease in SHBG levels. Three of the patients treated with triptorelin alone experienced tumor regression compared with four patients in the combination group. No appreciable side effects of the combination therapy were observed. Conclusion: The treatment of premenopausal patients with triptorelin plus 4-OHA is feasible and leads to a much greater inhibition of main circulating estrogens than treatment with the analog alone. Since the combination of a GnRH analog and an aromatase inhibitor might potentially enhance the anti-tumor efficacy of the analog alone owing to more favorable endocrine effects, such a therapeutic approach deserves more extensive evaluation in the clinical setting.",
keywords = "Aromatase inhibition, Formestane, GnRH analog, Premenopausal breast cancer",
author = "Luigi Celio and Antonia Martinetti and Leonardo Ferrari and Roberto Buzzoni and Luigi Mariani and Rosalba Miceli and Ettore Seregni and Giuseppe Procopio and Antonio Cassata and Emilio Bombardieri and Emilio Bajetta",
year = "1999",
language = "English",
volume = "19",
pages = "2261--2268",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "3 B",

}

TY - JOUR

T1 - Premenopausal breast cancer patients treated with a gonadotropin-releasing hormone analog alone or in combination with an aromatase inhibitor

T2 - A comparative endocrine study

AU - Celio, Luigi

AU - Martinetti, Antonia

AU - Ferrari, Leonardo

AU - Buzzoni, Roberto

AU - Mariani, Luigi

AU - Miceli, Rosalba

AU - Seregni, Ettore

AU - Procopio, Giuseppe

AU - Cassata, Antonio

AU - Bombardieri, Emilio

AU - Bajetta, Emilio

PY - 1999

Y1 - 1999

N2 - Background: The combination of a GnRH analogue and an aromatase inhibitor can induce a complete estrogen blockade in premenopausal breast cancer patients. Material and Methods: Twenty-one premenopausal women with advanced breast cancer were randomised to receive the GnRH analog triptorelin (3.75 mg im monthly; n = 10) alone or in combination with the aromatase inhibitor formestane (4-OHA, 500 mg im fortnightly; n = 11) to compare the effect of both treatments on the patients' estrogenic milieu. Therefore, serum estrogen, gonadotropin and sex hormone-binding globulin (SHBG) levels were investigated before the start of treatment and subsequently over a three-month period. Results: There was a significant between-group difference in estrogen suppression during therapy. In comparison with baseline values, after four weeks of treatment the estradiol levels decreased by an average of 86.9% (95% CI, 70.5-94.2%) in the group treated with triptorelin alone and by 97.3% (95% CI, 94.1-98.8%; P = 0.0422) in the combination group; the respective figures for estrone were 48.5% (95% CI, 27.5-63.5%) and 70.4% (95% CI, 52.3-81.6%; P = 0.0007) and for estrone sulfate 56.7% (95% CI, 40-68.8%) and 80.5% (95% CI, 69.4-87.6%; P = 0.0055). No difference was observed between the groups in terms of gonadotropin suppression; both treatment modalities led to a slight but delayed decrease in SHBG levels. Three of the patients treated with triptorelin alone experienced tumor regression compared with four patients in the combination group. No appreciable side effects of the combination therapy were observed. Conclusion: The treatment of premenopausal patients with triptorelin plus 4-OHA is feasible and leads to a much greater inhibition of main circulating estrogens than treatment with the analog alone. Since the combination of a GnRH analog and an aromatase inhibitor might potentially enhance the anti-tumor efficacy of the analog alone owing to more favorable endocrine effects, such a therapeutic approach deserves more extensive evaluation in the clinical setting.

AB - Background: The combination of a GnRH analogue and an aromatase inhibitor can induce a complete estrogen blockade in premenopausal breast cancer patients. Material and Methods: Twenty-one premenopausal women with advanced breast cancer were randomised to receive the GnRH analog triptorelin (3.75 mg im monthly; n = 10) alone or in combination with the aromatase inhibitor formestane (4-OHA, 500 mg im fortnightly; n = 11) to compare the effect of both treatments on the patients' estrogenic milieu. Therefore, serum estrogen, gonadotropin and sex hormone-binding globulin (SHBG) levels were investigated before the start of treatment and subsequently over a three-month period. Results: There was a significant between-group difference in estrogen suppression during therapy. In comparison with baseline values, after four weeks of treatment the estradiol levels decreased by an average of 86.9% (95% CI, 70.5-94.2%) in the group treated with triptorelin alone and by 97.3% (95% CI, 94.1-98.8%; P = 0.0422) in the combination group; the respective figures for estrone were 48.5% (95% CI, 27.5-63.5%) and 70.4% (95% CI, 52.3-81.6%; P = 0.0007) and for estrone sulfate 56.7% (95% CI, 40-68.8%) and 80.5% (95% CI, 69.4-87.6%; P = 0.0055). No difference was observed between the groups in terms of gonadotropin suppression; both treatment modalities led to a slight but delayed decrease in SHBG levels. Three of the patients treated with triptorelin alone experienced tumor regression compared with four patients in the combination group. No appreciable side effects of the combination therapy were observed. Conclusion: The treatment of premenopausal patients with triptorelin plus 4-OHA is feasible and leads to a much greater inhibition of main circulating estrogens than treatment with the analog alone. Since the combination of a GnRH analog and an aromatase inhibitor might potentially enhance the anti-tumor efficacy of the analog alone owing to more favorable endocrine effects, such a therapeutic approach deserves more extensive evaluation in the clinical setting.

KW - Aromatase inhibition

KW - Formestane

KW - GnRH analog

KW - Premenopausal breast cancer

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M3 - Article

C2 - 10472341

AN - SCOPUS:0032805333

VL - 19

SP - 2261

EP - 2268

JO - Anticancer Research

JF - Anticancer Research

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ER -