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Relationship between crown-like structures and sex-steroid hormones in breast adipose tissue and serum among postmenopausal breast cancer patients

BACKGROUND: Postmenopausal obesity is associated with increased circulating levels of androgens and estrogens and elevated breast cancer risk. Crown-like structures (CLS; microscopic foci of dying adipocytes surrounded by macrophages) are proposed to represent sites of increased aromatization of and...

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Autores principales: Mullooly, Maeve, Yang, Hannah P., Falk, Roni T., Nyante, Sarah J., Cora, Renata, Pfeiffer, Ruth M., Radisky, Derek C., Visscher, Daniel W., Hartmann, Lynn C., Carter, Jodi M., Degnim, Amy C., Stanczyk, Frank Z., Figueroa, Jonine D., Garcia-Closas, Montserrat, Lissowska, Jolanta, Troester, Melissa A., Hewitt, Stephen M., Brinton, Louise A., Sherman, Mark E., Gierach, Gretchen L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244534/
https://www.ncbi.nlm.nih.gov/pubmed/28103902
http://dx.doi.org/10.1186/s13058-016-0791-4
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author Mullooly, Maeve
Yang, Hannah P.
Falk, Roni T.
Nyante, Sarah J.
Cora, Renata
Pfeiffer, Ruth M.
Radisky, Derek C.
Visscher, Daniel W.
Hartmann, Lynn C.
Carter, Jodi M.
Degnim, Amy C.
Stanczyk, Frank Z.
Figueroa, Jonine D.
Garcia-Closas, Montserrat
Lissowska, Jolanta
Troester, Melissa A.
Hewitt, Stephen M.
Brinton, Louise A.
Sherman, Mark E.
Gierach, Gretchen L.
author_facet Mullooly, Maeve
Yang, Hannah P.
Falk, Roni T.
Nyante, Sarah J.
Cora, Renata
Pfeiffer, Ruth M.
Radisky, Derek C.
Visscher, Daniel W.
Hartmann, Lynn C.
Carter, Jodi M.
Degnim, Amy C.
Stanczyk, Frank Z.
Figueroa, Jonine D.
Garcia-Closas, Montserrat
Lissowska, Jolanta
Troester, Melissa A.
Hewitt, Stephen M.
Brinton, Louise A.
Sherman, Mark E.
Gierach, Gretchen L.
author_sort Mullooly, Maeve
collection PubMed
description BACKGROUND: Postmenopausal obesity is associated with increased circulating levels of androgens and estrogens and elevated breast cancer risk. Crown-like structures (CLS; microscopic foci of dying adipocytes surrounded by macrophages) are proposed to represent sites of increased aromatization of androgens to estrogens. Accordingly, we examined relationships between CLS and sex-steroid hormones in breast adipose tissue and serum from postmenopausal breast cancer patients. METHODS: Formalin-fixed paraffin embedded benign breast tissues collected for research from postmenopausal women (n = 83) diagnosed with invasive breast cancer in the Polish Breast Cancer Study (PBCS) were evaluated. Tissues were immunohistochemically stained for CD68 to determine the presence of CLS per unit area of adipose tissue. Relationships were assessed between CD68 density and CLS and previously reported sex-steroid hormones quantified using radioimmunoassays in serum taken at the time of diagnosis and in fresh frozen adipose tissue taken at the time of surgery. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relationships between hormones (in tertiles) and CLS. RESULTS: CLS were observed in 36% of benign breast tissues, with a higher frequency among obese versus lean women (54% versus 17%, p = 0.03). Detection of CLS was not related to individual hormone levels or breast tumor pathology characteristics. However, detection of CLS was associated with hormone ratios. Compared with women in the highest tertile of estrone:androstenedione ratio in fat, those in the lowest tertile were less likely to have CLS (OR 0.12, 95% CI 0.03–0.59). A similar pattern was observed with estradiol:testosterone ratio in serum and CLS (lowest versus highest tertile, OR 0.18, 95% CI 0.04–0.72). CONCLUSIONS: CLS were more frequently identified in the breast fat of obese women and were associated with increased ratios of select estrogens:androgens in the blood and tissues, but not with individual hormones. Additional studies on CLS, tissue and blood hormone levels, and breast cancer risk are needed to understand and confirm these findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-016-0791-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-52445342017-01-23 Relationship between crown-like structures and sex-steroid hormones in breast adipose tissue and serum among postmenopausal breast cancer patients Mullooly, Maeve Yang, Hannah P. Falk, Roni T. Nyante, Sarah J. Cora, Renata Pfeiffer, Ruth M. Radisky, Derek C. Visscher, Daniel W. Hartmann, Lynn C. Carter, Jodi M. Degnim, Amy C. Stanczyk, Frank Z. Figueroa, Jonine D. Garcia-Closas, Montserrat Lissowska, Jolanta Troester, Melissa A. Hewitt, Stephen M. Brinton, Louise A. Sherman, Mark E. Gierach, Gretchen L. Breast Cancer Res Research Article BACKGROUND: Postmenopausal obesity is associated with increased circulating levels of androgens and estrogens and elevated breast cancer risk. Crown-like structures (CLS; microscopic foci of dying adipocytes surrounded by macrophages) are proposed to represent sites of increased aromatization of androgens to estrogens. Accordingly, we examined relationships between CLS and sex-steroid hormones in breast adipose tissue and serum from postmenopausal breast cancer patients. METHODS: Formalin-fixed paraffin embedded benign breast tissues collected for research from postmenopausal women (n = 83) diagnosed with invasive breast cancer in the Polish Breast Cancer Study (PBCS) were evaluated. Tissues were immunohistochemically stained for CD68 to determine the presence of CLS per unit area of adipose tissue. Relationships were assessed between CD68 density and CLS and previously reported sex-steroid hormones quantified using radioimmunoassays in serum taken at the time of diagnosis and in fresh frozen adipose tissue taken at the time of surgery. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relationships between hormones (in tertiles) and CLS. RESULTS: CLS were observed in 36% of benign breast tissues, with a higher frequency among obese versus lean women (54% versus 17%, p = 0.03). Detection of CLS was not related to individual hormone levels or breast tumor pathology characteristics. However, detection of CLS was associated with hormone ratios. Compared with women in the highest tertile of estrone:androstenedione ratio in fat, those in the lowest tertile were less likely to have CLS (OR 0.12, 95% CI 0.03–0.59). A similar pattern was observed with estradiol:testosterone ratio in serum and CLS (lowest versus highest tertile, OR 0.18, 95% CI 0.04–0.72). CONCLUSIONS: CLS were more frequently identified in the breast fat of obese women and were associated with increased ratios of select estrogens:androgens in the blood and tissues, but not with individual hormones. Additional studies on CLS, tissue and blood hormone levels, and breast cancer risk are needed to understand and confirm these findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-016-0791-4) contains supplementary material, which is available to authorized users. BioMed Central 2017-01-19 2017 /pmc/articles/PMC5244534/ /pubmed/28103902 http://dx.doi.org/10.1186/s13058-016-0791-4 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Mullooly, Maeve
Yang, Hannah P.
Falk, Roni T.
Nyante, Sarah J.
Cora, Renata
Pfeiffer, Ruth M.
Radisky, Derek C.
Visscher, Daniel W.
Hartmann, Lynn C.
Carter, Jodi M.
Degnim, Amy C.
Stanczyk, Frank Z.
Figueroa, Jonine D.
Garcia-Closas, Montserrat
Lissowska, Jolanta
Troester, Melissa A.
Hewitt, Stephen M.
Brinton, Louise A.
Sherman, Mark E.
Gierach, Gretchen L.
Relationship between crown-like structures and sex-steroid hormones in breast adipose tissue and serum among postmenopausal breast cancer patients
title Relationship between crown-like structures and sex-steroid hormones in breast adipose tissue and serum among postmenopausal breast cancer patients
title_full Relationship between crown-like structures and sex-steroid hormones in breast adipose tissue and serum among postmenopausal breast cancer patients
title_fullStr Relationship between crown-like structures and sex-steroid hormones in breast adipose tissue and serum among postmenopausal breast cancer patients
title_full_unstemmed Relationship between crown-like structures and sex-steroid hormones in breast adipose tissue and serum among postmenopausal breast cancer patients
title_short Relationship between crown-like structures and sex-steroid hormones in breast adipose tissue and serum among postmenopausal breast cancer patients
title_sort relationship between crown-like structures and sex-steroid hormones in breast adipose tissue and serum among postmenopausal breast cancer patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244534/
https://www.ncbi.nlm.nih.gov/pubmed/28103902
http://dx.doi.org/10.1186/s13058-016-0791-4
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