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- W4361943763 abstract "<div>Abstract<p><b>Purpose:</b> The concentration of estradiol (E<sub>2</sub>) in breast tumors is significantly higher than that in plasma, particularly in postmenopausal women. The contribution of local E<sub>2</sub> synthesis versus uptake of E<sub>2</sub> from the circulation is controversial. Our aim was to identify possible determinants of intratumoral E<sub>2</sub> levels in breast cancer patients.</p><p><b>Experimental Design:</b> The expression of genes involved in estrogen synthesis, metabolism, and signaling was measured in 34 matched samples of breast tumor and normal breast tissue, and their correlation with estrogen concentrations assessed.</p><p><b>Results:</b> <i>ESR1</i> (9.1-fold; <i>P</i> < 0.001) and <i>HSD17B7</i> (3.5-fold; <i>P</i> < 0.001) were upregulated in ER<sup>+</sup> tumors compared with normal tissues, whereas <i>STS</i> (0.34-fold; <i>P</i> < 0.001) and <i>HSD17B5</i> (0.23-fold; <i>P</i> < 0.001) were downregulated. Intratumoral E<sub>2</sub> levels showed a strong positive correlation with <i>ESR1</i> expression in all patients (Spearman <i>r</i> = 0.55, <i>P</i> < 0.001) and among the subgroups of postmenopausal (<i>r</i> = 0.76, <i>P</i> < 0.001; <i>n</i> = 23) and postmenopausal ER<sup>+</sup> patients (<i>r</i> = 0.59, <i>P</i> = 0.013; <i>n</i> = 17). <i>HSD17B7</i> expression showed a significant positive correlation (<i>r</i> = 0.59, <i>P</i> < 0.001) whereas <i>HSD17B2</i> (<i>r</i> = −0.46, <i>P</i> = 0.0057) and <i>HSD17B12</i> (<i>r</i> = −0.45, <i>P</i> = 0.0076) showed significant negative correlations with intratumoral E<sub>2</sub> in all patients. Intratumoral E<sub>2</sub> revealed no correlation to <i>CYP19, STS</i>, and <i>HSD17B1</i> expression. Multivariate models comprising <i>ESR1</i> and plasma E<sub>2</sub> predicted between 50% and 70% of intratumoral E<sub>2</sub> variability.</p><p><b>Conclusion:</b> Uptake due to binding to the ER, rather than intratumoral estrogen synthesis by aromatase or sulfatase, is the single most important correlate and a probable determinant of intratumoral E<sub>2</sub>. An increased expression of <i>HSD17B7</i> may explain the increased ratio of E<sub>2</sub> to estrone (E<sub>1</sub>) in breast tumors compared with normal tissue. Clin Cancer Res; 16(6); 1790–801</p></div>" @default.
- W4361943763 created "2023-04-05" @default.
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- W4361943763 date "2023-03-31" @default.
- W4361943763 modified "2023-10-18" @default.
- W4361943763 title "Data from Intratumoral Estrogen Disposition in Breast Cancer" @default.
- W4361943763 doi "https://doi.org/10.1158/1078-0432.c.6519440" @default.
- W4361943763 hasPublicationYear "2023" @default.
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