Role of HER3 expression and PTEN loss in patients with HER2-overexpressing metastatic breast cancer (MBC) who received taxane plus trastuzumab treatment

Yh, Park; Ha, Jung Min; Mk, Choi; Chang, Won Jin; Choi, Yong; Ig, Do; Js, Ahn; Im, Y-H.

doi:10.1038/bjc.2013.757

Cited by 46 publications

(48 citation statements)

References 31 publications

(38 reference statements)

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“…85 Several studies have demonstrated that HER3 is frequently co-expressed with HER2 in breast cancer, and HER3 has a role in HER2-mediated breast carcinogenesis. 86,87 Iorio et al 81 suggested that the reintroduction of miR-205 into SKBr3 cell increases the responsiveness of lapatinib (tyrosine kinase inhibitors) avoiding HER3-mediated resistance and restoring potent proapoptotic activity. Wang et al 88 predicted that miR-205 binds to the 3′ untranslated regions of HER3 mRNA, and the upregulation of miR-205 reduced HER3 protein expression.…”

Section: Mirna In Hormone Receptor-positive/her2-negative Breast Cancermentioning

confidence: 99%

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

et al. 2016

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MicroRNAs (miRNAs) are short non-coding RNAs that regulate the function of target genes at the post-transcriptional phase. miRNAs are considered to have roles in the development, progression and metastasis of cancer. Recent studies have indicated that particular miRNA signatures are correlated with tumor aggressiveness, response to drug therapy and patient outcome in breast cancer. On the other hand, in routine clinical practice, the treatment regimens for breast cancer are determined based on the intrinsic subtype of the primary tumor. Previous studies have shown that miRNA expression profiles of each intrinsic subtypes of breast cancer differ. In hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, miRNA expressions are found to be correlated with endocrine therapy resistance, progesterone receptor expression and heat shock protein activity. Some miRNAs are associated with resistance to HER2-targeted therapy and HER3 expression in HER2-positive breast cancer. In triple-negative breast cancer, miRNA expressions are found to be associated with BRCA mutations, immune system, epithelial-mesenchymal transition, cancer stem cell properties and androgen receptor expression. As it has been clarified that the expression levels and functions of miRNA differ among the various subtypes of breast cancer, and it is necessary to take account of the characteristics of each breast cancer subtype during research into the roles of miRNA in breast cancer. In addition, the discovery of the roles played by miRNAs in breast cancer might provide new opportunities for the development of novel strategies for diagnosing and treating breast cancer.

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Section: Mirna In Hormone Receptor-positive/her2-negative Breast Cancermentioning

confidence: 99%

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

et al. 2016

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“…In HER2-amplified breast cancers, it is the HER2/HER3 heterodimer which is largely responsible for driving tumour growth. Poor response to HER2-targeted therapies (for instance trastuzumab) in these patients is believed, in part, to be associated with increased expression of HER3 [46].…”

Section: Her2-egfp and Her3-mrfp1mentioning

confidence: 99%

A high speed multifocal multiphoton fluorescence lifetime imaging microscope for live-cell FRET imaging

Poland¹,

Krstajić²,

Monypenny³

et al. 2015

Biomed. Opt. Express

106

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Abstract:We demonstrate diffraction limited multiphoton imaging in a massively parallel, fully addressable time-resolved multi-beam multiphoton microscope capable of producing fluorescence lifetime images with sub50ps temporal resolution. This imaging platform offers a significant improvement in acquisition speed over single-beam laser scanning FLIM by a factor of 64 without compromising in either the temporal or spatial resolutions of the system. We demonstrate FLIM acquisition at 500 ms with live cells expressing green fluorescent protein. The applicability of the technique to imaging protein-protein interactions in live cells is exemplified by observation of time-dependent FRET between the epidermal growth factor receptor (EGFR) and the adapter protein Grb2 following stimulation with the receptor ligand. Furthermore, ligand-dependent association of HER2-HER3 receptor tyrosine kinases was observed on a similar timescale and involved the internalisation and accumulation or receptor heterodimers within endosomes. These data demonstrate the broad applicability of this novel FLIM technique to the spatio-temporal dynamics of protein-protein interaction. 73-76 (1990). 9. F. Helmchen and W. Denk, "Deep tissue two-photon microscopy," Nat. Methods 2(12), 932-940 (2005). 10. J. Bewersdorf, R. Pick, and S. W. Hell, "Multifocal multiphoton microscopy," Opt. Lett. 23(9), 655-657 (1998) ©2015 Optical Society of America

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“…In this study, patients with a higher H3T level frequently responded to LC therapy, but not significantly. Park et al [11] found that HER3 and PTEN expressions were predictive markers, and that PTEN expression was a predictive and prognostic biomarker for Tmab treatment in HER2-positive metastatic breast cancer. PTEN status and liver metastasis could predict the clinical efficacy of subsequent lapatinib therapy [31].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, p95 immunohistochemical expression using the same antibody did not correlate with the outcomes [10]. Patients who had negative HER3 staining had a better PFS than those who had positive HER3 staining, and patients who had a higher PTEN score showed longer PFS than those with a lower PTEN score [11]. In the neoadjuvant setting, HER2-positive breast carcinomas with a PIK3CA mutation are less likely to achieve pCR after neoadjuvant chemotherapy plus anti-HER2 treatment even if dual anti-HER2 treatment is given.…”

Section: Introductionmentioning

confidence: 99%

Role of HER2-Related Biomarkers (HER2, p95HER2, HER3, PTEN, and PIK3CA) in the Efficacy of Lapatinib plus Capecitabine in HER2-Positive Advanced Breast Cancer Refractory to Trastuzumab

Nishimura¹,

Toh

Tanaka³

et al. 2017

Oncology

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Objective: The aim of this study was to investigate the correlation between human epidermal growth factor receptor 2 (HER2)-related biomarkers and the treatment outcomes using lapatinib plus capecitabine (LC) and to evaluate the influence of the estrogen receptor (ER) status in trastuzumab-refractory HER2-positive advanced breast cancer. Method: Eighty patients were enrolled in this study. Total HER2, p95HER2, and total HER3 expression were quantified using the VeraTag assays. PTEN (phosphatase and tensin homolog) and p95 expression was evaluated using immunohistochemistry and PIK3CA mutation using direct sequencing. Results: The response rate to LC was 30%, clinical benefit rate was 51.3%, and the median progression-free survival (PFS) was 174.5 days. ER negativity significantly correlated with higher HER2 and p95HER2. The lower HER2 and PIK3CA mutations were often observed in the nonresponders. A high p95HER2 expression correlated with longer PFS especially in the high HER2- and ER-positive cases. Patients without the PIK3CA mutation showed longer PFS in the same subset. Overall survival after LC significantly correlated with the number of recurrence organs. Conclusion: LC therapy is effective in trastuzumab-refractory HER2-positive breast cancer. Moreover, the biomarker expression differed depending on ER status, and a high p95HER2 expression and wild-type PIK3CA gene correlated with longer PFS especially in the ER-positive cases.

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Role of HER3 expression and PTEN loss in patients with HER2-overexpressing metastatic breast cancer (MBC) who received taxane plus trastuzumab treatment

Abstract: Background: The aim of this study was to investigate the role of human epidermal growth factor receptor (HER3) and PTEN expression in patients with HER2-overexpressing metastatic breast cancer (MBC).

Cited by 46 publications

References 31 publications

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

A high speed multifocal multiphoton fluorescence lifetime imaging microscope for live-cell FRET imaging

Role of HER2-Related Biomarkers (HER2, p95HER2, HER3, PTEN, and PIK3CA) in the Efficacy of Lapatinib plus Capecitabine in HER2-Positive Advanced Breast Cancer Refractory to Trastuzumab

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