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

Background: The combination of a GnRH analogue and an aromatase inhibitor c an induce a complete estrogen blockade in premenopausal breast cancer patie nts. Material and Methods: Twenty-one premenopausal women with advanced bre ast cancer were randomised to receive the GnKH analog triptorelin (3.75 mg im monthly; n=10) alone or in combination with the aromatase inhibitor form estane (4-OHA, 500 mg im fortnightly; n=11) to compare the effect of both t reatments on the patients' estrogenic milieu. Therefore, serum estrogen, go nadotropin 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 suppr ession 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% C I, 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 sligh t but delayed decrease in SHBG levels. Three of the patients treated with t riptorelin alone experienced tumor regression compared with four patients i n the combination group. No appreciable side effects of the combination the rapy 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 t he combination of a GnRH analog and an aromatase inhibitor might potentiall y enhance the anti-tumor efficacy of the analog alone owing to more favorab le endocrine effects, such a therapeutic approach deserves more extensive e valuation in the clinical setting.