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

• Published in: Anticancer research Vol. 19; no. 3B; p. 2261
• Main Authors: Celio, L, Martinetti, A, Ferrari, L, Buzzoni, R, Mariani, L, Miceli, R, Seregni, E, Procopio, G, Cassata, A, Bombardieri, E, Bajetta, E
• Format: Journal Article
• Language: English
• Published: Greece 01-05-1999
• Subjects: Adult; Androstenedione - administration & dosage; Androstenedione - analogs & derivatives; Androstenedione - therapeutic use; Antineoplastic Agents - antagonists & inhibitors; Antineoplastic Agents - therapeutic use; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Aromatase Inhibitors; Breast Neoplasms - blood; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Breast Neoplasms - physiopathology; Estradiol - blood; Estrone - blood; Female; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Premenopause; Receptors, Estrogen - analysis; Receptors, Progesterone - analysis; Sex Hormone-Binding Globulin - analysis; Triptorelin Pamoate - administration & dosage; Triptorelin Pamoate - therapeutic use
• ISSN: 0250-7005

The combination of a GnRH analogue and an aromatase inhibitor can induce a complete estrogen blockade in premenopausal breast cancer patients.
Twenty-one premenopausal women with advanced breast cancer were randomised to receive the GnRH analog triptorelin (3.75 mg i.m. monthly; n = 10) alone or in combination with the aromatase inhibitor formestane (4-OHA, 500 mg i.m. 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.
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.
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.