Estrogen sulfates are quantitatively the most important form of circulating
estrogens during the menstrual cycle and in the post-menopausal period. Huge quantities of
estrone sulfate and
estradiol sulfate are found in the breast tissues of patients with mammary
carcinoma. It has been demonstrated that different estrogen-3-sulfates (estrone-3-sulfate, estradiol-3-sulfate, estriol-3-sulfate) can provoke important
biological responses in different
mammary cancer cell lines: there is a significant increase in
progesterone receptor. On the other hand, no significant effect was observed with estrogen-17-sulfates. The reason for the
biological response of estrogen-3-sulfates is that these
sulfates are hydrolyzed, and no
sulfatase activity for C17-sulfates is present in these cell lines. [3H]
Estrone sulfate is converted in a very high percentage to
estradiol (E2) in different
hormone-dependent
mammary cancer cell lines (MCF-7, R-27, T-47D), but very little or no conversion was found in the
hormone-independent
mammary cancer cell lines (MDA-MB-231, MDA-MB-436). Different anti-
estrogens (
tamoxifen and derivatives) and another potent anti-
estrogen: ICI 164,384, decrease the concentration of
estradiol very significantly after incubation of
estrone sulfate with the different
hormone-dependent
mammary cancer cell lines. No significant effect was observed for the uptake and conversion of
estrone sulfate in the
hormone-independent
mammary cancer cell lines.
Progesterone provokes an important decrease in the uptake and in
estradiol levels after incubation of [3H]
estrone sulfate with the MCF-7 cells. It is concluded that in
breast cancer: (1)
Estrogen sulfates can play an important role in the
biological response of
estrogens; (2) Anti-
estrogens and
progesterone significantly decrease the uptake and
estradiol levels in
hormone-dependent
mammary cancer cell lines; (3) The control of the
sulfatase and 17 beta-
hydroxysteroid dehydrogenase activities, which are key steps in the formation of
estradiol in the breast, can open new possibilities in the treatment of
hormone-dependent
mammary cancer.