Bioavailability of estradiol as a marker for breast cancer risk assessment.

The search for a hormonal marker in breast cancer has centered on estrogens and their metabolites. However, direct measurements of total amounts of these steroids have shown no convincing or consistent differences between normal women and women with breast cancer. The purpose of this study was to measure the percentages of non-protein-bound estradiol (%NPBE) and of estradiol bound to albumin (%ABE) and the levels of sex hormone-binding globulin (SHBG) both in women with breast cancer and in those free of disease. Serum was collected and analyzed within 2 weeks, using an isodialysis method. The mean %NPBE and %ABE were significantly higher in 32 women with breast cancer (1.73 and 64.0%, respectively) than in 32 matched disease-free women (1.43 and 48.6%, respectively) (P less than 0.001). No significant difference was observed in the levels of plasma albumin when the above matched groups were compared. However, plasma levels of SHBG were significantly lower in the women with breast cancer than in either the control population or matched controls. In this finding we differ from previous studies which reported no significant differences in the mean plasma levels of SHBG. In our study, the increased %NPBE and %ABE in some patients with breast cancer may be related to a lower level of plasma SHBG; other factors, too, may affect the distribution of estradiol. Our results support the hypothesis than an increase in %NPBE and %ABE or both may indicate an increased risk of breast cancer.