Prognostic value of plasma prostate specific antigen after megestrol acetate treatment in patients with metastatic breast carcinoma

BACKGROUND. Prostate specific antigen (PSA) is an established tumor marker of prostate adenocarcinoma that recently also was found in breast tumors. M inute amounts of PSA are found in female plasma. It is known from cell cult ure studies that PSA expression can be up-regulated by androgens and proges tins but not estrogens. In this study, the authors examined whether plasma PSA in women with breast carcinoma changes after the therapeutic administra tion of the progestin megestrol acetate (MA) and whether these changes have any prognostic value. METHODS. Plasma PSA was measured by a highly sensitive immunofluorometric p rocedure that can measure within 1 ng/L of PSA. Serial plasma levels from w omen with metastatic breast carcinoma who received either MA (N = 52) or ot her treatments (N = 24] were evaluated. PSA changes in plasma were correlat ed with patient outcomes. RESULTS. The study found that approximately 50% of the patients receiving M A had a significant increase in their plasma PSA concentration after the tr eatment and that this increase was,rapid (starting within I week) and dose- dependent. PSA levels declined when treatment was withdrawn. Further compar isons with similar groups of patients receiving tamoxifen or doxorubicin ha ve shown that the plasma PSA increases are specific to the MA treatment. Th e plasma PSA increases reflect the stimulation of the tumor by MA to produc e PSA and the secretion of PSA into the general circulation. There is a sta tistically significant association between the plasma PSA changes after MA treatment and overall patient survival; patients with increased plasma PSA have an approximate threefold increase in their relative risk of death duri ng the follow-up period. Multivariate analysis has shown that the increased risk of death in this group is associated, at least in part, with the freq uent presence of distant metastasis. CONCLUSIONS. The measurement of plasma PSA after treatment with MA allows f or patient classification into two groups. The group that did not demonstra te any changes in their plasma PSA level after MA treatment (approximately 50% of the patients) had a significantly better prognosis. The group that d id demonstrate an increase in their plasma PSA level after MA treatment rep resented a subset of patients who may benefit more from MA withdrawal and t he initiation of alternative regimens. However, these data need further con firmation with a larger pool of patients. (C) 1999 American Cancer Society.