Tumor response and estrogen suppression in breast cancer patients treated with aromatase inhibitors

Background: The rationale for the hormonal treatment of breast cancer (BC) is based on depriving tumor cells of estrogenic stimulation. Aromatase inhi bitors (AIs) block the conversion of peripheral tissue androgens to estroge ns with different levels of potency. In an attempt to investigate the relat ionship between tumor response and estrogen suppression, we reviewed the ho rmonal and clinical data of two previous studies with formestane (250 and 5 00 mg i.m. fortnightly) in advanced BC patients. Patients and methods: Two hundred four BC patients were selected on the bas is of the availability of records concerning their plasma estrone (E1) and estradiol (E2) levels assessed at scheduled times. The degree of estrogen s uppression and the best clinical response of each patient during the trials were considered. Results: There was a positive and significant (P < 0.05) correlation betwee n baseline and post-formestane E1 and E2 levels, with a decrease in the lev els of both hormones irrespective of any antitumor response. In particular, the degree of plasma estrogen suppression was similar in the patients who experienced a complete remission and those with progressive disease (PD). Conclusions: The plasma estrogen suppression induced by aromatase inhibitio n is not the only mechanism accounting for its clinical activity. Many clin ical trials have demonstrated that all AIs induce a similar antitumor respo nse regardless of their potency, and further investigations are warranted i n order to improve our understanding as to why the patients with PD also sh ow a significant plasma estrogen suppression. It is possible that intratumo ral aromatase activity may be a marker for selecting the BC patients most l ikely to respond to AI treatment.