The Emerging Role of ESR1 Mutations in Luminal Breast Cancer as a Prognostic and Predictive Biomarker of Response to Endocrine Therapy

Santo, De; McCartney, Amelia; Migliaccio, Ilenia; Leo, Angelo Di; Malorni, Luca

doi:10.3390/cancers11121894

Cited by 60 publications

(40 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The top ranked putative regulator in luminal breast invasive carcinoma (BRCA luminal) was ESR1, which has been previously shown as a predictive biomarker of breast cancer. These results agree with previous studies on breast cancer that estrogen receptors and ESR1 mutations are markers of poor prognosis (14).…”

Section: Trs For Up-regulated Genessupporting

confidence: 93%

BART Cancer: a web resource for transcriptional regulators in cancer genomes

Thomas

Wang

Zang

2020

Preprint

View full text Add to dashboard Cite

Dysregulation of gene expression plays an important role in cancer development. Identifying transcriptional regulators, including transcription factors and chromatin regulators, that drive the oncogenic gene expression program is a critical task in cancer research. Genomic profiles of active transcriptional regulators from primary cancer samples are limited in the public domain. Here we present BART Cancer (bartcancer.org), an interactive web resource database to display the putative transcriptional regulators that are responsible for differentially regulated genes in 15 different cancer types in The Cancer Genome Atlas (TCGA). BART Cancer integrates over 10,000 gene expression profiling RNA-seq datasets from TCGA with over 7,000 ChIP-seq datasets from the Cistrome Data Browser database and the Gene Expression Omnibus (GEO). BART Cancer uses Binding Analysis for Regulation of Transcription (BART) for predicting the transcriptional regulators from the differentially expressed genes in cancer samples compared to normal samples. BART Cancer also displays the activities of over 900 transcriptional regulators across cancer types, by integrating computational prediction results from BART and the Cistrome Cancer database. Focusing on transcriptional regulator activities in human cancers, BART Cancer can provide unique insights into epigenetics and transcriptional regulation in cancer, and is a useful data resource for genomics and cancer research communities.

show abstract

Section: Trs For Up-regulated Genessupporting

confidence: 93%

BART Cancer: a web resource for transcriptional regulators in cancer genomes

Thomas

Wang

Zang

2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Rearrangements of ESR1 can trigger endocrine resistance, and some hotspot ESR1 mutations can activate ER transcription, which was reported to promote hormone-independent tumor cell growth by ligand-independent ER activity in breast cancer. 26 However, in patient 2 the expression of ESR1 was decreased after drug resistance so could not explain the failure of the ALK inhibitors. On the other hand, PTCH1 has the highest FPKM value among all the genes with expression change, and the degree of its reduction almost reached one hundred folds.…”

Section: Discussionmentioning

confidence: 94%

<p>Efficacy and Resistance of ALK Inhibitors in Two Inflammatory Myofibroblastic Tumor Patients with ALK Fusions Assessed by Whole Exome and RNA Sequencing</p>

Zhang¹,

Wang²,

Zhuang³

et al. 2020

OTT

View full text Add to dashboard Cite

We report two inflammatory myofibroblastic tumor (IMT) patients with ALK fusions (RRBP-ALK and TNS1-ALK, respectively). They both received tumor resection surgery and treatment with ALK inhibitors crizotinib followed by alectinib, and upon receiving each of the drugs, showed a brief response, then experienced recurrence or progression of the disease. During the treatment, whole exome sequencing (WES) and RNA sequencing (RNA-Seq) were applied to monitor potential drug-induced gene mutation and expression changes. A novel, secondary mutation in ALK exon 23 (L1196Q) was identified in patient 1 after alectinib resistance developed. Guided by this result, a newer ALK inhibitor, ceritinib was prescribed. The patient was able to achieve a partial response (PR) and is in good condition as of the manuscript date. On the contrary, there was no secondary mutation identified in ALK in patient 2 after drug resistance. While the expression of PTCH1, a negative regulator of the sonic hedgehog (SHH) signaling pathway, was significantly reduced at the time after the treatment with crizotinib before that of alectinib. The expression of PTCH1 was also reduced after the treatment with alectinib. It was reported that ALK can exert its biological functions partially by activating SHH signaling pathway. The down-regulation of PTCH1 suggests the compensatory activation of SHH pathway may cause resistance to ALK inhibitors in IMT. Going forward, monitoring gene mutation and expression changes through DNA and RNA sequencing will be able to offer opportunities to investigate potential mechanisms of drug resistance and will help to achieve precise prescription for better treatment outcomes.

show abstract

“…Clinical phase 1 trials are currently testing several oral selective estrogen receptor degrader (SERD) including G1T48 (ClinicalTrials. gov identifier: NCT03455270) in metastatic endocrine resistant luminal breast cancer harboring ESR1 mutations [86]. Despite these novel developments the clinical integration of routine testing for ESR1 mutations needs further validation.…”

Section: Molecular Profiling Of Advanced Luminal Breast Cancermentioning

confidence: 99%

Genomic Signatures in Luminal Breast Cancer

et al. 2020

View full text Add to dashboard Cite

Background: Breast cancer is a very heterogeneous disease and luminal breast carcinomas represent the hormone receptor-positive tumors among all breast cancer subtypes. In this context, multigene signatures were developed to gain further prognostic and predictive information beyond clinical parameters and traditional immunohistochemical markers. Summary: For early breast cancer patients these molecular tools can guide clinicians to decide on the extension of endocrine therapy to avoid over-and undertreatment by adjuvant chemotherapy. Beside the predictive and prognostic value, a few genomic tests are also able to provide intrinsic subtype classification. In this review, we compare the most frequently used and commercially available molecular tests (OncotypeDX ® , MammaPrint ® , Prosigna ® , EndoPredict ® , and Breast Cancer Index SM). Moreover, we discuss the clinical utility of molecular profiling for advanced breast cancer of the luminal subtype. Key Messages: Multigene assays can help to de-escalate systemic therapy in early-stage breast cancer. Only the Oncotype DX ® and MammaPrint ® test are validated by entirely prospective and randomized phase 3 trials. More clinical evidence is needed to support the use of genomic tests in node-positive disease. Recent developments in high-throughput sequencing technology will provide further insights to understand the heterogeneity of luminal breast cancers in early-stage and metastatic disease.

show abstract

The Emerging Role of ESR1 Mutations in Luminal Breast Cancer as a Prognostic and Predictive Biomarker of Response to Endocrine Therapy

Cited by 60 publications

References 71 publications

BART Cancer: a web resource for transcriptional regulators in cancer genomes

BART Cancer: a web resource for transcriptional regulators in cancer genomes

<p>Efficacy and Resistance of ALK Inhibitors in Two Inflammatory Myofibroblastic Tumor Patients with ALK Fusions Assessed by Whole Exome and RNA Sequencing</p>

Genomic Signatures in Luminal Breast Cancer

Contact Info

Product

Resources

About