Progesterone receptor A predominance is a discriminator of benefit from endocrine therapy in the ATAC trial
- PMID: 25917868
- DOI: 10.1007/s10549-015-3397-0
Progesterone receptor A predominance is a discriminator of benefit from endocrine therapy in the ATAC trial
Abstract
Progesterone receptor (PR) function, while essential in normal human breast, is also implicated in breast cancer risk. The two progesterone receptors, PRA and PRB, are co-expressed at equivalent levels in normal breast, but early in carcinogenesis normal levels of PRA:PRB are frequently disrupted, and predominance of one isoform, usually PRA, results. In model systems, PRA and PRB have different activities, and altering the PRA:PRB ratio in cell lines alters PR signaling. The purpose of this study was to determine whether hormonal or reproductive factors contribute to imbalanced PRA:PRB expression in breast tumors and the impact of PRA:PRB imbalance on disease outcome. The relative expression of PRA and PRB proteins was determined by dual immunofluorescence histochemistry in archival breast tumors and associations with clinical and reproductive history assessed. PRA:PRB expression was not influenced by reproductive factors, whereas exogenous hormone use (menopausal hormone treatment, MHT) favored PRB expression (p < 0.035). The PRA:PRB ratio may be a discriminator of response to endocrine therapy in the TransATAC sample collection, with high PRA:PRB ratio predicting earlier relapse for women on tamoxifen, but not anastrozole (mean lnPRA:PRB ratio; HR (95 % CI) tamoxifen 2.45 (1.20-4.99); p value 0.02; anastrozole 0.80 (0.36-1.78); p value 0.60). The results of this study show that PRA:PRB imbalance in breast cancers is not associated with lifetime endogenous endocrine and reproductive factors, but is associated with MHT use, and that PRA predominance can discriminate those women who will relapse earlier on tamoxifen treatment. These data support a role for imbalanced PRA:PRB expression in breast cancer progression and relative benefit from endocrine treatment.
Similar articles
-
Differential regulation of breast cancer-associated genes by progesterone receptor isoforms PRA and PRB in a new bi-inducible breast cancer cell line.PLoS One. 2012;7(9):e45993. doi: 10.1371/journal.pone.0045993. Epub 2012 Sep 24. PLoS One. 2012. PMID: 23029355 Free PMC article.
-
Progesterone receptor isoform-specific promoter methylation: association of PRA promoter methylation with worse outcome in breast cancer patients.Clin Cancer Res. 2011 Jun 15;17(12):4177-86. doi: 10.1158/1078-0432.CCR-10-2950. Epub 2011 Apr 1. Clin Cancer Res. 2011. PMID: 21459801 Free PMC article.
-
Role of the progesterone receptor (PR) and the PR isoforms in breast cancer.Crit Rev Oncog. 2007 Dec;13(4):283-301. doi: 10.1615/critrevoncog.v13.i4.20. Crit Rev Oncog. 2007. PMID: 18540831 Review.
-
Progesterone receptor isoforms in normal and malignant breast.Ernst Schering Found Symp Proc. 2007;(1):77-107. Ernst Schering Found Symp Proc. 2007. PMID: 18540569 Review.
-
Loss of co-ordinate expression of progesterone receptors A and B is an early event in breast carcinogenesis.Breast Cancer Res Treat. 2002 Mar;72(2):163-72. doi: 10.1023/a:1014820500738. Breast Cancer Res Treat. 2002. PMID: 12038707
Cited by
-
Targeting nuclear hormone receptors for the prevention of breast cancer.Front Med (Lausanne). 2023 Jul 31;10:1200947. doi: 10.3389/fmed.2023.1200947. eCollection 2023. Front Med (Lausanne). 2023. PMID: 37583424 Free PMC article. Review.
-
Biomarkers in Breast Cancer: An Old Story with a New End.Genes (Basel). 2023 Jun 28;14(7):1364. doi: 10.3390/genes14071364. Genes (Basel). 2023. PMID: 37510269 Free PMC article. Review.
-
Unexplored Functions of Sex Hormones in Glioblastoma Cancer Stem Cells.Endocrinology. 2022 Mar 1;163(3):bqac002. doi: 10.1210/endocr/bqac002. Endocrinology. 2022. PMID: 35023543 Free PMC article. Review.
-
Steroid Receptors in Breast Cancer: Understanding of Molecular Function as a Basis for Effective Therapy Development.Cancers (Basel). 2021 Sep 24;13(19):4779. doi: 10.3390/cancers13194779. Cancers (Basel). 2021. PMID: 34638264 Free PMC article. Review.
-
Lost but Not Least-Novel Insights into Progesterone Receptor Loss in Estrogen Receptor-Positive Breast Cancer.Cancers (Basel). 2021 Sep 23;13(19):4755. doi: 10.3390/cancers13194755. Cancers (Basel). 2021. PMID: 34638241 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials