Prostate-specific antigen (PSA) is a serine protease expressed at high leve
ls in prostate epithelium, and elevated PSA in serum is a well-established
marker of prostate cancer. Recently, the relative proportions of free PSA a
nd PSA complexed to the serine protease inhibitor alpha(1)-antichymotrypsin
have become important variables in distinguishing between prostate cancer
and benign prostatic hyperplasia, Numerous studies have demonstrated the pr
oduction of PSA in female tissues such as the breast, and low levels of PSA
are present in female sera. The objective of this study was to measure and
compare the relative proportions of free PSA and PSA complexed to the seri
ne protease inhibitor cw,antichymotrypsin in the serum of women with breast
cancer or benign breast disease or women with no known malignancies. PSA w
as measured,vith an established immunoassay for total PSA and a novel immun
oassay for free PSA, both of which had a detection limit of 0.001 mu g/lite
r (1 ng/liter), The percentage of breast cancer patients,vith free PSA as t
he predominant molecular form (>50% of total PSA) in serum was five times h
igher than that of healthy women or women with benign breast disease, and P
SA decreased in the serum of breast cancer patients after surgery. The diag
nostic use of free PSA for breast cancer is limited at this point, due to t
he low diagnostic sensitivity (similar to 20%); however, free PSA as the pr
edominant molecular form shows a high diagnostic specificity (similar to 96
%) in comparison to women free of breast cancer or with benign breast disea
se. These results suggest that the clinical applicability of free PSA for b
reast cancer diagnosis and the biological mechanism behind its increase sho
uld be further investigated.