Therapeutic resistance to anti-oestrogen therapy in breast cancer

Will, Marie; Liang, Jackson; Metcalfe, Ciara; Chandarlapaty, Sarat

doi:10.1038/s41568-023-00604-3

Cited by 27 publications

(10 citation statements)

References 156 publications

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“…As previously discussed, ESR1 alterations are acquired in HR+/HER2- BC under the selective pressure of AIs, and predict poor sensitivity to further aromatase inhibition 17 . Given the dynamic and subclonal nature of the alteration, liquid biopsy represents the appropriate tool for ESR1 mutations detection during ET.…”

Section: Tumor Genotyping For Treatment Selectionmentioning

confidence: 77%

“…The ESR1 mutation has long been known as an acquired resistance mechanism to endocrine treatment with aromatase inhibitors (AIs), by inducing constitutive activation of the estrogen receptor (ER). Virtually absent in untreated mBC, its incidence averages 20-40% in mBCs previously exposed to AIs 17 . Exploratory analyses from the SoFEA and EFECT studies, evaluating the effectiveness of exemestane versus fulvestrant following progression to nonsteroidal AIs in HR+/HER2- mBC, suggested the clinical utility of ESR1 mutation detection in ctDNA to select patients more likely to benefit from fulvestrant 18 – 21 .…”

Section: Tumor Genotyping For Treatment Selectionmentioning

confidence: 96%

“…On the other hand, ctDNA alterations could provide hints on intracellular pathways activity. For instance, besides defining patients eligibility for treatment with elacestrant, the presence of ESR1 mutations in ctDNA suggests that the disease retains endocrine sensitivity, once constitutive activation of the ER is circumvented by treatment 17 . This concept is also supported by the evidence of a greater PFS benefit from elacestrant in patients with longer response to CDK4/6 inhibition, suggesting a greater endocrine sensitivity of the disease 60 .…”

Section: Tumor Genotyping For Treatment Selectionmentioning

confidence: 99%

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Circulating tumor DNA validity and potential uses in metastatic breast cancer

Amato,

Giannopoulou,

Ignatiadis

2024

npj Breast Cancer

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Following the first characterization of circulating tumor DNA (ctDNA) in the 1990s, recent advances led to its introduction in the clinics. At present, the European Society Of Medical Oncology (ESMO) recommendations endorse ctDNA testing in routine clinical practice for tumor genotyping to direct molecularly targeted therapies in patients with metastatic cancer. In studies on metastatic breast cancer, ctDNA has been utilized for treatment tailoring, tracking mechanisms of drug resistance, and for predicting disease response before imaging. We review the available evidence regarding ctDNA applications in metastatic breast cancer.

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Section: Tumor Genotyping For Treatment Selectionmentioning

confidence: 77%

Section: Tumor Genotyping For Treatment Selectionmentioning

confidence: 96%

Section: Tumor Genotyping For Treatment Selectionmentioning

confidence: 99%

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Circulating tumor DNA validity and potential uses in metastatic breast cancer

Amato,

Giannopoulou,

Ignatiadis

2024

npj Breast Cancer

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“…The mortality of female breast cancer has decreased due to mammography, earlier diagnose and improved therapy. Treatment modalities include lumpectomy, mastectomy, chemotherapy, radiation therapy, targeted therapy, hormone therapy and immunotherapy [ 5 – 7 ]. However, because of metastasis and drug resistance [ 8 ], breast cancer is the second greatest numbers of deaths after lung cancer in women in the United States [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Fbxo45 facilitates the malignant progression of breast cancer by targeting Bim for ubiquitination and degradation

Zheng,

Wu,

Xiao

et al. 2024

BMC Cancer

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Background Breast cancer is one of the common malignancies in women. Evidence has demonstrated that FBXO45 plays a pivotal role in oncogenesis and progression. However, the role of FBXO45 in breast tumorigenesis remains elusive. Exploration of the regulatory mechanisms of FBXO45 in breast cancer development is pivotal for potential therapeutic interventions in patients with breast cancer. Methods Hence, we used numerous approaches to explore the functions of FBXO45 and its underlaying mechanisms in breast cancer pathogenesis, including CCK-8 assay, EdU assay, colony formation analysis, apoptosis assay, RT-PCR, Western blotting, immunoprecipitation, ubiquitination assay, and cycloheximide chase assay. Results We found that downregulation of FBXO45 inhibited cell proliferation, while upregulation of FBXO45 elevated cell proliferation in breast cancer. Silencing of FBXO45 induced cell apoptosis, whereas overexpression of FBXO45 inhibited cell apoptosis in breast cancer. Moreover, FBXO45 interacted with BIM and regulated its ubiquitination and degradation. Furthermore, knockdown of FBXO45 inhibited cell proliferation via regulation of BIM pathway. Notably, overexpression of FBXO45 facilitated tumor growth in mice. Strikingly, FBXO45 expression was associated with poor survival of breast cancer patients. Conclusion Our study could provide the rational for targeting FBXO45 to obtain benefit for breast cancer patients. Altogether, modulating FBXO45/Bim axis could be a promising strategy for breast cancer therapy.

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“…Breast cancer exhibits diversity at the biological level, with prognosis being impacted by a range of factors such as molecular subtypes, age at diagnosis, and histopathological features ( Brown et al, 2023 ). Recent advancements in early detection methods for breast cancer and the ongoing progress in treatment options have greatly enhanced the outlook for patients with this disease ( Will et al, 2023 ; Brown et al, 2024 ). Especially as people’s understanding of the immune microenvironment deepens, the utility of immunotherapy in breast cancer treatment continues to ascend.…”

Section: Introductionmentioning

confidence: 99%

Unraveling breast cancer prognosis: a novel model based on coagulation-related genes

Lei,

Li,

Yang

et al. 2024

Front. Mol. Biosci.

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ObjectiveBreast cancer is highly heterogeneous, presenting challenges in prognostic assessment. Developing a universally applicable prognostic model could simplify clinical decision-making. This study aims to develop and validate a novel breast cancer prognosis model using coagulation-related genes with broad clinical applicability.MethodsA total of 203 genes related to coagulation were obtained from the KEGG database, and the mRNA data of 1,099 tumor tissue samples and 572 samples of normal tissue were retrieved from the TCGA-BRCA cohort and GTEx databases. The R package “limma” was utilized to detect variations in gene expression related to coagulation between the malignancies and normal tissue. A model was constructed in the TCGA cohort through a multivariable Cox regression analysis, followed by validation using the GSE42568 dataset as the testing set. Constructing a nomogram incorporating clinical factors to enhance the predictive capacity of the model. Utilizing the ESTIMATE algorithm to investigate the immune infiltration levels in groups with deferent risk. Performing drug sensitivity analysis using the “oncoPredict” package.ResultsA risk model consisting of six coagulation-associated genes (SERPINA1, SERPINF2, C1S, CFB, RASGRP1, and TLN2) was created and successfully tested for validation. Identified were 6 genes that serve as protective factors in the model’s development. Kaplan-Meier curves revealed a worse prognosis in the high-risk group compared to the low-risk group. The ROC analysis showed that the model accurately forecasted the overall survival (OS) of breast cancer patients at 1, 3, and 5 years. Nomogram accompanied by calibration curves can also provide better guidance for clinical decision-making. The low-risk group is more likely to respond well to immunotherapy, whereas the high-risk group may show improved responses to Gemcitabine treatment. Furthermore, individuals in distinct risk categories displayed different responses to various medications within the identical therapeutic category.ConclusionWe established a breast cancer prognostic model incorporating six coagulation-associated genes and explored its clinical utility. This model offers valuable insights for clinical decision-making and drug selection in breast cancer patients, contributing to personalized and precise treatment advancements.

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Therapeutic resistance to anti-oestrogen therapy in breast cancer

Cited by 27 publications

References 156 publications

Circulating tumor DNA validity and potential uses in metastatic breast cancer

Circulating tumor DNA validity and potential uses in metastatic breast cancer

Fbxo45 facilitates the malignant progression of breast cancer by targeting Bim for ubiquitination and degradation

Unraveling breast cancer prognosis: a novel model based on coagulation-related genes

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