Estrogen Receptor-Positive Breast Cancer: Exploiting Signaling Pathways Implicated in Endocrine Resistance

Brufsky, Adam; Dickler, Maura N.

doi:10.1634/theoncologist.2017-0423

Cited by 110 publications

(95 citation statements)

References 90 publications

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“…In breast cancer, the majority of tumors are luminal ER + and require estrogen and ER for their growth [59]. While the majority of ER + breast cancer patients respond to endocrine therapies, a significant fraction develops resistance and progresses to metastatic disease [60]. KDM5B was identified as an oncogene commonly amplified and overexpressed in luminal ER + breast tumors and higher KDM5B activity was associated with poor outcome in ER + breast cancer patients treated with endocrine therapy [61].…”

Section: Epigenetic Regulation Of Transcriptomic Heterogeneitymentioning

confidence: 99%

Intratumoral Heterogeneity: More Than Just Mutations

Hinohara

Polyák

2019

Trends in Cell Biology

169

144

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Most human tumors are composed of genetically and phenotypically heterogeneous cancer cell populations that poses a major challenge for the clinical management of cancer patients. Advances of single cell technologies have allowed the profiling of tumors at unprecedented depth, which in combination with newly-developed computational tools enable the dissection of tumor evolution with increasing precision. However, our understanding of mechanisms that regulate intratumoral heterogeneity and our ability to modulate it has been lagging behind. Recent data demonstrate that epigenetic regulators, including histone demethylases, may control the cell-to-cell variability of transcriptomes and chromatin profiles and they may modulate therapeutic responses via this function. Thus, the therapeutic targeting of epigenetic enzymes may be used to decrease intratumoral cellular heterogeneity and decrease treatment resistance when used in combination with other types of agents.

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Section: Epigenetic Regulation Of Transcriptomic Heterogeneitymentioning

confidence: 99%

Intratumoral Heterogeneity: More Than Just Mutations

Hinohara

Polyák

2019

Trends in Cell Biology

169

144

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“…ERα is more frequently expressed in luminal A tumors than in basal tumors [ 54 ]. ERα-positive cases are not only responsive to endocrine therapies, but also sensitive to CDK4/6 inhibitors [ 55 , 56 ]. Thus, ER positivity may be associated with a better prognosis [ 57 ].…”

Section: Expression Of Er In Human Tumorsmentioning

confidence: 99%

Mechanisms for estrogen receptor expression in human cancer

et al. 2018

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Estrogen is a steroid hormone that has critical roles in reproductive development, bone homeostasis, cardiovascular remodeling and brain functions. However, estrogen also promotes mammary, ovarian and endometrial tumorigenesis. Estrogen antagonists and drugs that reduce estrogen biosynthesis have become highly successful therapeutic agents for breast cancer patients. The effects of estrogen are largely mediated by estrogen receptor (ER) α and ERβ, which are members of the nuclear receptor superfamily of transcription factors. The mechanisms underlying the aberrant expression of ER in breast cancer and other types of human tumors are complex, involving considerable alternative splicing of ERα and ERβ, transcription factors, epigenetic and post-transcriptional regulation of ER expression. Elucidation of mechanisms for ER expression may not only help understand cancer progression and evolution, but also shed light on overcoming endocrine therapy resistance. Herein, we review the complex mechanisms for regulating ER expression in human cancer.

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“…Because there are many classes of treatment options (endocrine therapy, biologics, cytotoxic chemotherapy, etc.) and a myriad of evolving disease phenotypes (loss of ER, gain of human epidermal growth receptor 2 [HER2], emergence of PI3Kinase mutations, ESR1, and others), determining a sequence of therapies is a major challenge for each individual patient [4][5][6]. Hormone receptor-directed therapy can only be effective if there is receptor expression in metastatic lesions.…”

Section: Introductionmentioning

confidence: 99%

Whole-Body Characterization of Estrogen Receptor Status in Metastatic Breast Cancer with 16α-18F-Fluoro-17β-Estradiol Positron Emission Tomography: Meta-Analysis and Recommendations for Integration into Clinical Applications

Kurland

Wiggins²,

Coche³

et al. 2020

The Oncologist

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Estrogen receptor (ER) status by immunohistochemistry (IHC) of cancer tissue is currently used to direct endocrine therapy in breast cancer. Positron emission tomography (PET) with 16α-18F-fluoro-17β-estradiol (18 F-FES) noninvasively characterizes ER ligand-binding function of breast cancer lesions. Concordance of imaging and tissue assays should be established for 18 F-FES PET to be an alternative or complement to tissue biopsy for metastatic lesions. We conducted a metaanalysis of published results comparing 18 F-FES PET and tissue assays of ER status in patients with breast cancer. PubMed and EMBASE were searched for English-language manuscripts with at least 10 patients and low overall risk of bias. Thresholds for imaging and tissue classification could differ between studies but had to be clearly stated. We used hierarchical summary receiver-operating characteristic curve models for the meta-analysis. The primary analysis included 113 nonbreast lesions from 4 studies; an expanded analysis included 327 total lesions from 11 studies. Treating IHC results as the reference standard, sensitivity was 0.78 (95% confidence region 0.65-0.88) and specificity 0.98 (0.65-1.00) for the primary analysis of nonbreast lesions. In the expanded analysis including non-IHC tissue assays and all lesion sites, sensitivity was 0.81 (0.73-0.87) and specificity 0.86 (0.68-0.94). These results suggest that 18 F-FES PET is useful for characterization of ER status of metastatic breast cancer lesions. We also review current best practices for conducting 18 F-FES PET scans. This imaging assay has potential to improve clinically relevant outcomes for patients with (historically) ER-positive metastatic breast cancer, including those with brain metastases and/or lobular histology.

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Estrogen Receptor-Positive Breast Cancer: Exploiting Signaling Pathways Implicated in Endocrine Resistance

Cited by 110 publications

References 90 publications

Intratumoral Heterogeneity: More Than Just Mutations

Intratumoral Heterogeneity: More Than Just Mutations

Mechanisms for estrogen receptor expression in human cancer

Whole-Body Characterization of Estrogen Receptor Status in Metastatic Breast Cancer with 16α-18F-Fluoro-17β-Estradiol Positron Emission Tomography: Meta-Analysis and Recommendations for Integration into Clinical Applications

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