Forty-six patients with advanced breast cancer were treated orally with high-dose medroxyprogesterone acetate (MPA), and a 28% (2 CRs, 11 PRs) response rate was obtained. The patient groups that showed a favorable response to MPA were as follows: patients in a postmenopausal state, with soft tissue or bone metastases, with slow-growing tumors, without prior therapy or with good response to prior endocrine therapy, and with positive estrogen (ER)- and/or progesterone (PgR) receptors. Six of 10 patients who had responded to prior endocrine therapy responded to MPA, while only 2 of 23 who had not responded to prior endocrine therapy showed a good response to MPA. There was a significant difference in response to MPA between patients with positive ER or PgR and those with negative ER or PgR tumors. The ER detected in primary or initially relapsed tumors correlated well with the effects of MPA given as a 2nd-line endocrine therapy for advanced breast cancer. The possible roles of MPA in the treatment of advanced breast cancer were discussed.