We investigated the aminogluthetimide therapy effect on 30 postmenopausal women with advanced breast cancer previously treated with tamoxifen as a first-line hormonal treatment. Aminogluthetimide exhibits anticancer effect by inhibition of aromatase enzyme which plays a key role in the conversion of androgen to estrogen in peripheral adipose tissue. This pathway presents the main source of estrogen in postmenopausal women. Mean duration of the treatment was 14.3 months. Complete remission has been achieved in 10% of all patients, and partial remission in 16.6%. Mean duration of free intervals was 16.1 months in the group with ER+/PgR+ hormonal status, which is significantly longer compared to the ER+/PgR- and ER-/PgR+ groups where it was 11.8 months (p < 0.01). Aminogluthetimide treatment led to significant decrease in estradiol (E2) and dehydroepiandrosterone-sulphate (DHAS) levels in plasma. Thus, the effect of aminogluthetimide therapy as a second-line hormonal therapy has a benefit in the treatment of metastatic hormon-dependent breast cancer patients.