Influence of plasma estrogen levels on the length of the disease-free interval in postmenopausal women with breast cancer

Summary The influence of plasma estrogen levels on disease-free interval (time from primary treatment to first relapse, DFI) in breast cancer patients is not known. Any relation between plasma estrogens and the outcome in breast cancer patients may have implications considering use of hormone replacement therapy (HRT) in patients treated for breast cancer. We measured plasma estradiol (E₂), estrone (E₁), and estrone sulfate (E₁S) in 92 postmenopausal women with breast cancer relapse and correlated plasma estrogen levels to the length of their disease-free interval (DFI₁) and the length of the DFI in the subgroup of patients in whom this extended a time period of more than 2 years (DFI₂). The length of DFI₂ correlated negatively to plasma level of E₁S (p < 0.025) and E₂ (p < 0.05) and to the E₂/E₁ and E₁S/E₁ ratios (p < 0.05), while the length of DFI₁ correlated negatively to plasma level of E₁S (p < 0.025) and the E₁S/E₁ ratio (p < 0.005). We also analyzed for possible correlations between DFIs and plasma estrogen levels in subgroups based on tumor stage at diagnosis and previous therapy. In general, these subgroup analyses revealed negative correlations of statistical significance or borderline significance between the DFI₁ and DFI₂ and E₂ and the E₂/E₁ ratio and non-significant negative correlations between plasma levels of E₁S and DFI₁ and DFI₂. In particular, strong negative correlations between plasma estrogen levels and the length of DFI₁ and DFI₂ were found among patients responding to first line endocrine treatment for relapse and among patients with primar stage III tumors. Our findings suggest plasma E₂ and E₁S to stimulate the growth of micrometastases in patients treated for breast cancer.