Biological subtypes of breast cancer: Prognostic and therapeutic implications

Yersal, Özlem; Barutça, Sabri

doi:10.5306/wjco.v5.i3.412

Cited by 802 publications

(689 citation statements)

References 86 publications

(80 reference statements)

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“…Our findings were in accordance with studies by Halmos et al (12), showing a significant positive correlation between ER expression and GRP-R binding affinity examined on isolated cell membranes from BC samples. Because ER-positive tumors account for 75% of all breast tumors, GRP-R-based imaging could offer new imaging and therapeutic possibilities for most BC patients (2,20). In addition, because current treatments with antihormonal agents, such as tamoxifen and aromatase inhibitors, are ineffective in about 40% of the ER-positive metastatic BC patients (20,21), GRP-R ligands radiolabeled with particle emitters might offer new therapeutic options for these patients.…”

Section: Discussionmentioning

confidence: 99%

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In Vitro and In Vivo Application of Radiolabeled Gastrin-Releasing Peptide Receptor Ligands in Breast Cancer

et al. 2015

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Breast cancer (BC) consists of multiple subtypes defined by various molecular characteristics, for instance, estrogen receptor (ER) expression. Methods for visualizing BC include mammography, MR imaging, ultrasound, and nuclear medicine-based methods such as 99m Tcsestamibi and 18 F-FDG PET, unfortunately all lacking specificity. Peptide receptor scintigraphy and peptide receptor radionuclide therapy are successfully applied for imaging and therapy of somatostatin receptor-expressing neuroendocrine tumors using somatostatin receptor radioligands. On the basis of a similar rationale, radioligands targeting the gastrin-releasing peptide receptor (GRP-R) might offer a specific method for imaging and therapy of BC. The aim of this study was to explore the application of GRP-R radioligands for imaging and therapy of BC by introducing valid preclinical in vitro and in vivo models. Methods: GRP-R expression of 50 clinical BC specimens and the correlation with ER expression was studied by in vitro autoradiography with the GRP-R agonist 111 In-AMBA. GRP-R expression was also analyzed in 9 BC cell lines applying 111 In-AMBA internalization assays and quantitative reverse transcriptase polymerase chain reaction. In vitro cytotoxicity of 177 Lu-AMBA was determined on the GRP-Rexpressing BC cell line T47D. SPECT/CT imaging and biodistribution were studied in mice with subcutaneous and orthotopic ER-positive T47D and MCF7 xenografts after injection of the GRP-R antagonist 111 In-JMV4168. Results: Most of the human BC specimens (96%) and BC cell lines (6/9) were found to express GRP-R. GRP-R tumor expression was positively (P 5 0.026, χ 2 (4) 5 12,911) correlated with ER expression in the human BC specimens. Treatment of T47D cells with 10 −7 M/50 MBq of 177 Lu-AMBA resulted in 80% reduction of cells in vitro. Furthermore, subcutaneous and orthotopic tumors from both BC cell lines were successfully visualized in vivo by SPECT/CT using 111 In-JMV4168; T47D tumors exhibited a higher uptake than MCF7 xenografts. Conclusion: Targeting GRP-R-expressing BC tumors using GRP-R radioligands is promising for nuclear imaging and therapy, especially in ER-positive BC patients.

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Section: Discussionmentioning

confidence: 99%

“…On the basis of molecular characteristics, BC can be divided in 4 subgroups: luminal A and B, human epidermal growth factor receptor 2-like, and triple-negative tumors (2). The treatment and prognosis of BC are highly dependent on this classification.…”

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confidence: 99%

In Vitro and In Vivo Application of Radiolabeled Gastrin-Releasing Peptide Receptor Ligands in Breast Cancer

et al. 2015

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“…Activating mutations on gene loci encoding the tyrosine kinase domain, or the overexpression of HER2 receptors, can lead to the upregulation or dysregulation of downstream signaling pathways (13). HER2 is overexpressed in 15-20% of breast carcinomas (1,14).…”

Section: Introductionmentioning

confidence: 99%

Trastuzumab as a preoperative monotherapy does not inhibit HER2 downstream signaling in HER2-positive breast cancer

Lion¹,

Harlé²,

Salleron³

et al. 2016

Oncology Letters

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Abstract. Human epidermal growth factor 2 (HER2) is overexpressed in 15-20% of breast carcinomas. The overexpression of HER2 was previously associated with a poor prognosis until the development of the first anti-HER2 therapy, trastuzumab, which drastically improves the prognosis of HER2-overexpressing breast cancers. However, its mechanism of action remains not fully understood. Several studies have proposed that the behavior and mechanism of action of trastuzumab may be drastically altered in vitro and in vivo. The present study assesses the ability of trastuzumab to inhibit the phosphorylation of the key-proteins of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin and Ras/Raf/mitogen-activated protein kinase (MAPK) signaling pathways in vitro, in breast cancer cell lines and in tumor biopsies obtained from patients treated with trastuzumab preoperative monotherapy as part of the Unicancer GEP04 RADHER phase II clinical trial. HER2-positive SKBR3 and HER2-negative MCF-7 cell lines were exposed to trastuzumab for 72 h. In total, 41 patients received trastuzumab alone for 6 weeks of preoperative treatment. Biopsies were collected at the baseline and at surgery. A total of 19 pairs of associated baseline and surgery tumor specimens were eligible for protein extraction and comparative phosphoprotein expression analysis, prior to and subsequent to treatment. The expression of phosphoproteins was quantitatively assessed using a multiplex immunoassay. In the SKBR3 cell line, a statistically significant decrease of the expression level of phosphorylated (p-)AKT, p-ribosomal protein S6 kinase B1, p-extracellular signal regulated kinase 1/2 and p-mitogen-activated protein kinase kinase 1 was observed after exposure to trastuzumab. In contrast, no statistically significant variations for levels expression of these phosphoproteins were observed in patients following treatment. The lack of downregulation of PI3K and MAPK pathways could probably be explained by the implementation of a predominant immunological mechanism of action for trastuzumab, a type of antibody-dependent cell-mediated toxicity, which has previously been reported in preoperative monotherapy settings. The present study confirms that trastuzumab involves various modes of action when assayed in vitro and used clinically.

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“…Ele possui diversos subtipos e por isso está associado a diferentes prognósticos e a diferentes respostas terapêuticas. Dentre eles, o subtipo triplo-negativo representa de 10 a 20% dos casos e apresenta pior prognóstico e maior taxa de recorrência (YERSAL, et al 2014;LEHMANN, et al 2011;CIRQUEIRA, et al 2011) Estudos vêm mostrando que o ácido eicosapentaenoico (EPA) e o ácido docosahexaenóico (DHA), ambos representantes da família ômega-3, possuem efeito antitumoral através da diminuição da proliferação celular e do aumento da morte por apoptose em células de câncer de mama CAO, et al 2012;XIONG, et al 2012).…”

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Efeitos do ácido docosahexaenoico (DHA) e do ácido araquidônico (AA) sobre a morte celular da linhagem celular de câncer de mama MDA-MB-231

Luzete¹

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Biological subtypes of breast cancer: Prognostic and therapeutic implications

Abstract: Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. Yersal O, Barutca S. Biological subtypes of breast cancer:

Cited by 802 publications

References 86 publications

In Vitro and In Vivo Application of Radiolabeled Gastrin-Releasing Peptide Receptor Ligands in Breast Cancer

In Vitro and In Vivo Application of Radiolabeled Gastrin-Releasing Peptide Receptor Ligands in Breast Cancer

Trastuzumab as a preoperative monotherapy does not inhibit HER2 downstream signaling in HER2-positive breast cancer

Efeitos do ácido docosahexaenoico (DHA) e do ácido araquidônico (AA) sobre a morte celular da linhagem celular de câncer de mama MDA-MB-231

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