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

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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