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. Minute amounts of PSA are found in female plasma. It is known from cell culture studies that PSA expression can be up-regulated by androgens and progestins but not estrogens. In this study, the authors examined whether plasma PSA in women with breast carcinoma changes after the therapeutic administration of the progestin megestrol acetate (MA) and whether these changes have any prognostic value.


METHODS
Plasma PSA was measured by a highly sensitive immunofluorometric procedure that can measure within 1 ng/L of PSA. Serial plasma levels from women with metastatic breast carcinoma who received either MA (N = 52) or other treatments (N = 24) were evaluated. PSA changes in plasma were correlated with patient outcomes.


RESULTS
The study found that approximately 50% of the patients receiving MA had a significant increase in their plasma PSA concentration after the treatment and that this increase was rapid (starting within 1 week) and dose-dependent. PSA levels declined when treatment was withdrawn. Further comparisons with similar groups of patients receiving tamoxifen or doxorubicin have shown that the plasma PSA increases are specific to the MA treatment. The plasma PSA increases reflect the stimulation of the tumor by MA to produce PSA and the secretion of PSA into the general circulation. There is a statistically 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 during 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 frequent presence of distant metastasis.


CONCLUSIONS
The measurement of plasma PSA after treatment with MA allows for patient classification into two groups. The group that did not demonstrate any changes in their plasma PSA level after MA treatment (approximately 50% of the patients) had a significantly better prognosis. The group that did demonstrate an increase in their plasma PSA level after MA treatment represented a subset of patients who may benefit more from MA withdrawal and the initiation of alternative regimens. However, these data need further confirmation with a larger pool of patients.
Diamandis
E P
EP
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
Helle
S I
SI
Yu
H
H
Melegos
D N
DN
Lundgren
S
S
Lonning
P E
PE
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D019290:Megestrol Acetate / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D011372:Progestins / Q000627:therapeutic use*; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D011372:Progestins; D013629:Tamoxifen; D017430:Prostate-Specific Antigen; D019290:Megestrol Acetate