To explore the different sequence interactions between reversible non-steroidal (anastrozole, ANZ and letrozole, LTZ) and non-reversible steroidal aromatase inhibitors (formestane, FOR and exemestane, EXE), we evaluated the clinical benefit (CB) in postmenopausal breast cancer patients, who had previously received anastrozole and subsequently formestane. In 19 out of 21 patients (90.5%), a clinical benefit response was achieved by anastrozole, with a median duration of 12 months. Out of the 21 women progressing on anastrozole, 12 achieved stable disease (SD)>/=6 months by formestane only. The overall clinical benefit was 66.5%. The median duration of clinical benefit was 11 months with a time to progression of 6.5 months. The median duration of clinical benefit in our series is similar to that reported in two phase II trials with the sequence aminogluthetimide-->formestane and aminogluthetimide-->exemestane as third-line hormonal therapy, suggesting a non-cross-resistance between the two classes of inhibitors.