GPER-1 expression is associated with a decreased response rate to primary tamoxifen therapy of breast cancer patients.
Breast cancer
GPER-1
GPR30
Tamoxifen resistance
Journal
Archives of gynecology and obstetrics
ISSN: 1432-0711
Titre abrégé: Arch Gynecol Obstet
Pays: Germany
ID NLM: 8710213
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
09
09
2019
accepted:
07
11
2019
pubmed:
5
1
2020
medline:
4
8
2020
entrez:
5
1
2020
Statut:
ppublish
Résumé
Endocrine therapies using tamoxifen and/or aromatase inhibitors are important therapeutic options for the targeted treatment of hormone-responsive breast cancer. In addition to nuclear estrogen receptors ERα and β, G-protein-coupled estrogen receptor GPER-1 is a third receptor-mediating estrogen effects in breast cancer cells. The aim of this study was to examine to what extent GPER-1 expression might affect the efficacy of primary endocrine treatment of breast cancer. GPER-1 expression was determined in tissue samples from patients with early breast cancer by means of immunohistochemistry and a GPER-1 score of ≥ 3 was considered to be positive. In a total of 165 patients, the response to a primary therapy with tamoxifen (TAM) or aromatase inhibitors (AI) was assessed by ultrasound imaging for up to 6 months. The primary endpoint of this study was the response to treatment evaluated by RECIST 1.1 criteria. GPER-1 expression was observed in 127 (77.0%) out of 165 cases. Based on GPER-1 expression and the type of endocrine treatment, the patients were divided into 4 groups: GPER-1 negative/TAM (12.1%), GPER-1 negative/AI (10.9%), GPER-1 positive/TAM (44.8%), and GPER-1 positive/AI (32.1%). The groups were well balanced regarding different clinical and pathological factors. After 4 and 6 months of treatment, a high level of stable disease or progressive disease was observed in the GPER-1 positive/TAM group only (p < 0.0001), whereas in the other three groups of patients, the most common objective response was classified as partial response. We observed a continuous reduction of mean tumor size in patients treated with aromatase inhibitors irrespective of the GPER-1 status and in GPER-1 negative patients treated with TAM. In contrast, in GPER-1 positive patients treated with TAM, a reduction of mean tumor size was observed only in the first 2 months after beginning of treatment. Four and six months after start of treatment, no reduction, but even a slight increase of tumor size was observed in this patients group. GPER-1 expression is significantly associated with a reduced effect of primary treatment with tamoxifen in breast cancer patients.
Identifiants
pubmed: 31900584
doi: 10.1007/s00404-019-05384-6
pii: 10.1007/s00404-019-05384-6
doi:
Substances chimiques
GPER1 protein, human
0
Receptors, Estrogen
0
Receptors, G-Protein-Coupled
0
Tamoxifen
094ZI81Y45
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
565-571Références
Ariazi EA, Brailoiu E, Yerrum S et al (2010) The G protein-coupled receptor GPR30 inhibits proliferation of estrogen receptor-positive breast cancer cells. Cancer Res 70:1184–1194
doi: 10.1158/0008-5472.CAN-09-3068
Broselid S, Cheng B, Sjostrom M et al (2013) G protein-coupled estrogen receptor is apoptotic and correlates with increased distant disease-free survival of estrogen receptor-positive breast cancer patients. Clin Cancer Res 19:1681–1692
doi: 10.1158/1078-0432.CCR-12-2376
Chan QK, Lam HM, Ng CF et al (2010) Activation of GPR30 inhibits the growth of prostate cancer cells through sustained activation of Erk1/2, c-jun/c-fos-dependent upregulation of p21, and induction of G(2) cell-cycle arrest. Cell Death Differ 17:1511–1523
doi: 10.1038/cdd.2010.20
Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247
doi: 10.1016/j.ejca.2008.10.026
Houssami N, Macaskill P, Von Minckwitz G et al (2012) Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy. Eur J Cancer 48:3342–3354
doi: 10.1016/j.ejca.2012.05.023
Ignatov A, Ignatov T, Roessner A et al (2010) Role of GPR30 in the mechanisms of tamoxifen resistance in breast cancer MCF-7 cells. Breast Cancer Res Treat 123:87–96
doi: 10.1007/s10549-009-0624-6
Ignatov A, Ignatov T, Weissenborn C et al (2011) G-protein-coupled estrogen receptor GPR30 and tamoxifen resistance in breast cancer. Breast Cancer Res Treat 128:457–466
doi: 10.1007/s10549-011-1584-1
Ignatov T, Modl S, Thulig M et al (2013) GPER-1 acts as a tumor suppressor in ovarian cancer. J Ovarian Res 6:51
doi: 10.1186/1757-2215-6-51
Ignatov T, Weissenborn C, Poehlmann A et al (2013) GPER-1 expression decreases during breast cancer tumorigenesis. Cancer Investig 31:309–315
doi: 10.3109/07357907.2013.789901
Ignatov T, Claus M, Nass N et al (2019) G-protein-coupled estrogen receptor GPER-1 expression in hormone receptor-positive breast cancer is associated with poor benefit of tamoxifen. Breast Cancer Res Treat 174:121–127
doi: 10.1007/s10549-018-5064-8
Liu Q, Chen Z, Jiang G et al (2017) Epigenetic down regulation of G protein-coupled estrogen receptor (GPER) functions as a tumor suppressor in colorectal cancer. Mol Cancer 16:87
doi: 10.1186/s12943-017-0654-3
Mo Z, Liu M, Yang F et al (2013) GPR30 as an initiator of tamoxifen resistance in hormone-dependent breast cancer. Breast Cancer Res 15:R114
doi: 10.1186/bcr3581
Molina L, Figueroa CD, Bhoola KD et al (2017) GPER-1/GPR30 a novel estrogen receptor sited in the cell membrane: therapeutic coupling to breast cancer. Expert Opin Ther Targets 21:755–766
doi: 10.1080/14728222.2017.1350264
Ribeiro MPC, Santos AE, Custodio JBA (2017) The activation of the G protein-coupled estrogen receptor (GPER) inhibits the proliferation of mouse melanoma K1735-M2 cells. Chem Biol Interact 277:176–184
doi: 10.1016/j.cbi.2017.09.017
Samartzis EP, Noske A, Meisel A et al (2014) The G protein-coupled estrogen receptor (GPER) is expressed in two different subcellular localizations reflecting distinct tumor properties in breast cancer. PLoS ONE 9:e83296
doi: 10.1371/journal.pone.0083296
Sjostrom M, Hartman L, Grabau D et al (2014) Lack of G protein-coupled estrogen receptor (GPER) in the plasma membrane is associated with excellent long-term prognosis in breast cancer. Breast Cancer Res Treat 145:61–71
doi: 10.1007/s10549-014-2936-4
Vivacqua A, Bonofiglio D, Recchia AG et al (2006) The G protein-coupled receptor GPR30 mediates the proliferative effects induced by 17β-estradiol and hydroxytamoxifen in endometrial cancer cells. Mol Endocrinol 20:631–646
doi: 10.1210/me.2005-0280
Von Elm E, Altman DG, Egger M et al (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370:1453–1457
doi: 10.1016/S0140-6736(07)61602-X
Weissenborn C, Ignatov T, Ochel HJ et al (2014) GPER functions as a tumor suppressor in triple-negative breast cancer cells. J Cancer Res Clin Oncol 140:713–723
doi: 10.1007/s00432-014-1620-8
Weissenborn C, Ignatov T, Poehlmann A et al (2014) GPER functions as a tumor suppressor in MCF-7 and SK-BR-3 breast cancer cells. J Cancer Res Clin Oncol 140:663–671
doi: 10.1007/s00432-014-1598-2
Weissenborn C, Ignatov T, Nass N et al (2017) GPER promoter methylation controls GPER expression in breast cancer patients. Cancer Investig 35:100–107
doi: 10.1080/07357907.2016.1271886