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Hormone replacement therapy dependent changes in breast cancer-related gene expression in breast tissue of healthy postmenopausal women.
Mol Oncol. 2011 Dec; 5(6):504-16.MO

Abstract

Risk assessment of future breast cancer risk through exposure to sex steroids currently relies on clinical scorings such as mammographic density. Knowledge about the gene expression patterns in existing breast cancer tumors may be used to identify risk factors in the breast tissue of women still free of cancer. The differential effects of estradiol, estradiol together with gestagens, or tibolone on breast cancer-related gene expression in normal breast tissue samples taken from postmenopausal women may be used to identify gene expression profiles associated with a higher breast cancer risk. Breast tissue samples were taken from 33 healthy postmenopausal women both before and after a six month treatment with either 2mg micronized estradiol [E2], 2mg micronized estradiol and 1mg norethisterone acetate [E2+NETA], 2.5mg tibolone [T] or [no HRT]. Except for [E2], which was only given to women after hysterectomy, the allocation to each of the three groups was randomized. The expression of 102 mRNAs and 46 microRNAs putatively involved in breast cancer was prospectively determined in the biopsies of 6 women receiving [no HRT], 5 women receiving [E2], 5 women receiving [E2+NETA], and 6 receiving [T]. Using epithelial and endothelial markers genes, non-representative biopsies from 11 women were eliminated. Treatment of postmenopausal women with [E2+NETA] resulted in the highest number of differentially (p<0.05) regulated genes (16.2%) compared to baseline, followed by [E2] (10.1%) and [T] (4.7%). Among genes that were significantly down-regulated by [E2+NETA] ranked estrogen-receptor-1 (ESR1, p=0.019) and androgen receptor (AR, p=0.019), whereas CYP1B1, a gene encoding an estrogen-metabolizing enzyme, was significantly up-regulated (p=0.016). Mammary cells triggered by [E2+NETA] and [E2] adjust for steroidogenic up-regulation through down-regulation of the estrogen-receptor pathway. In this prospective study, prolonged administration of [E2+NETA] and to a lesser extent of [E2] but not [T] were associated in otherwise healthy breast tissue with a change in the expression of genes putatively involved in breast cancer. Our data suggest that normal mammary cells triggered by [E2+NETA] adjust for steroidogenic up-regulation through down-regulation of the estrogen-receptor pathway. This feasibility study provides the basis for whole genome analyses to identify novel markers involved in increased breast cancer risk.

Authors+Show Affiliations

Department of Medical Oncology, Josephine Nefkens Institute, Cancer Genomics Centre, Erasmus Medical Center, Rotterdam, Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21956102

Citation

Sieuwerts, Anieta M., et al. "Hormone Replacement Therapy Dependent Changes in Breast Cancer-related Gene Expression in Breast Tissue of Healthy Postmenopausal Women." Molecular Oncology, vol. 5, no. 6, 2011, pp. 504-16.
Sieuwerts AM, De Napoli G, van Galen A, et al. Hormone replacement therapy dependent changes in breast cancer-related gene expression in breast tissue of healthy postmenopausal women. Mol Oncol. 2011;5(6):504-16.
Sieuwerts, A. M., De Napoli, G., van Galen, A., Kloosterboer, H. J., de Weerd, V., Zhang, H., Martens, J. W., Foekens, J. A., & De Geyter, C. (2011). Hormone replacement therapy dependent changes in breast cancer-related gene expression in breast tissue of healthy postmenopausal women. Molecular Oncology, 5(6), 504-16. https://doi.org/10.1016/j.molonc.2011.09.003
Sieuwerts AM, et al. Hormone Replacement Therapy Dependent Changes in Breast Cancer-related Gene Expression in Breast Tissue of Healthy Postmenopausal Women. Mol Oncol. 2011;5(6):504-16. PubMed PMID: 21956102.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hormone replacement therapy dependent changes in breast cancer-related gene expression in breast tissue of healthy postmenopausal women. AU - Sieuwerts,Anieta M, AU - De Napoli,Giuseppina, AU - van Galen,Anne, AU - Kloosterboer,Helenius J, AU - de Weerd,Vanja, AU - Zhang,Hong, AU - Martens,John W M, AU - Foekens,John A, AU - De Geyter,Christian, Y1 - 2011/09/16/ PY - 2011/08/09/received PY - 2011/09/10/revised PY - 2011/09/12/accepted PY - 2011/9/30/entrez PY - 2011/10/1/pubmed PY - 2012/3/14/medline SP - 504 EP - 16 JF - Molecular oncology JO - Mol Oncol VL - 5 IS - 6 N2 - Risk assessment of future breast cancer risk through exposure to sex steroids currently relies on clinical scorings such as mammographic density. Knowledge about the gene expression patterns in existing breast cancer tumors may be used to identify risk factors in the breast tissue of women still free of cancer. The differential effects of estradiol, estradiol together with gestagens, or tibolone on breast cancer-related gene expression in normal breast tissue samples taken from postmenopausal women may be used to identify gene expression profiles associated with a higher breast cancer risk. Breast tissue samples were taken from 33 healthy postmenopausal women both before and after a six month treatment with either 2mg micronized estradiol [E2], 2mg micronized estradiol and 1mg norethisterone acetate [E2+NETA], 2.5mg tibolone [T] or [no HRT]. Except for [E2], which was only given to women after hysterectomy, the allocation to each of the three groups was randomized. The expression of 102 mRNAs and 46 microRNAs putatively involved in breast cancer was prospectively determined in the biopsies of 6 women receiving [no HRT], 5 women receiving [E2], 5 women receiving [E2+NETA], and 6 receiving [T]. Using epithelial and endothelial markers genes, non-representative biopsies from 11 women were eliminated. Treatment of postmenopausal women with [E2+NETA] resulted in the highest number of differentially (p<0.05) regulated genes (16.2%) compared to baseline, followed by [E2] (10.1%) and [T] (4.7%). Among genes that were significantly down-regulated by [E2+NETA] ranked estrogen-receptor-1 (ESR1, p=0.019) and androgen receptor (AR, p=0.019), whereas CYP1B1, a gene encoding an estrogen-metabolizing enzyme, was significantly up-regulated (p=0.016). Mammary cells triggered by [E2+NETA] and [E2] adjust for steroidogenic up-regulation through down-regulation of the estrogen-receptor pathway. In this prospective study, prolonged administration of [E2+NETA] and to a lesser extent of [E2] but not [T] were associated in otherwise healthy breast tissue with a change in the expression of genes putatively involved in breast cancer. Our data suggest that normal mammary cells triggered by [E2+NETA] adjust for steroidogenic up-regulation through down-regulation of the estrogen-receptor pathway. This feasibility study provides the basis for whole genome analyses to identify novel markers involved in increased breast cancer risk. SN - 1878-0261 UR - https://www.unboundmedicine.com/medline/citation/21956102/Hormone_replacement_therapy_dependent_changes_in_breast_cancer_related_gene_expression_in_breast_tissue_of_healthy_postmenopausal_women_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1574-7891(11)00113-X DB - PRIME DP - Unbound Medicine ER -