Mechanism of resistance to endocrine therapy in breast cancer: the important role of PI3K/Akt/mTOR in estrogen receptor-positive, HER2-negative breast cancer

Araki, Kazuhiro; Miyoshi, Yasuo

doi:10.1007/s12282-017-0812-x

Cited by 142 publications

(109 citation statements)

References 96 publications

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“…Moreover, the pathways they use, i.e ., the PI3K/AKT and Ras/Raf/MEK/ERK pathways, may have activating mutations, e.g ., in components such as PI3K, which in turn may lead to ER activation[22]. To date, this information has been used to develop combination drug approaches that combine an endocrine agent with an inhibitor ( e.g ., HER2, PI3K, mTOR, CDK inhibitor, etc .)…”

Section: Development Of Endocrine Resistancementioning

confidence: 99%

Predictive markers of endocrine response in breast cancer

Mosly

Turnbull

Sims

et al. 2018

WJEM

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Ongoing clinical and research efforts seek to optimise the use of endocrine therapy in the treatment of breast cancer. Accurate biomarkers are needed that predict response for individual patients. The presence of the estrogen receptor (ER) as the direct (for tamoxifen and fulvestrant) or indirect (for aromatase inhibitors) target molecule for endocrine therapy remains the foremost biomarker and determinant of response. However, ER expression only poorly predicts outcome and further indicators of response or resistance are required. The development and application of molecular signature assays such as Oncotype Dx, Prosigna, Mammaprint and Endopredict have provided valuable information on prognosis and these are being used to support clinical decision making on whether endocrine therapy alone alongside surgery is sufficient for ER-positive early stage breast cancers or whether combination of endocrine with chemotherapy are also warranted. Ki67, the proliferation marker, has been widely used in the neo-adjuvant (pre-operative) setting to help predict response and long term outcome. Gene expression studies within the same setting have allowed monitoring of changes of potential predictive markers. These have identified frequent changes in estrogen-regulated and proliferation genes. Specific molecules such as mutant ER may also prove helpful biomarkers in predicting outcome and monitoring response to treatment.

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Section: Development Of Endocrine Resistancementioning

confidence: 99%

Predictive markers of endocrine response in breast cancer

Mosly

Turnbull

Sims

et al. 2018

WJEM

View full text Add to dashboard Cite

show abstract

“…Accordingly, extensive research has gone into studying the different mechanisms of resistance to both endocrine [123][124][125] and anti-HER2 therapies [90,126,127], leading to an increasing understanding of how alterations in the proteins targeted by treatment, their coactivators or related signalling pathways contribute to the development of the resistant phenotype. These studies may help identify novel treatment targets and inform new combinatorial therapeutic strategies.…”

Section: Alterations In Receptors As Novel Biomarkers To Improve Manamentioning

confidence: 99%

The evolving role of receptors as predictive biomarkers for metastatic breast cancer

Martínez-Pérez

Turnbull

Dixon

2018

Expert Review of Anticancer Therapy

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Introduction:In breast cancer, oestrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) are essential biomarkers to predict response to endocrine and anti-HER2 therapies, respectively. In metastatic breast cancer, the use of these receptors and targeted therapies present additional challenges: temporal heterogeneity, together with limited sampling methodologies, hinders receptor status assessment and the constant evolution of the disease invariably leads to resistance to treatment. Areas covered:We summarise genomic abnormalities in ER and HER2, such as mutations, amplifications, translocations and alternative splicing, emerging as novel biomarkers that provide an insight into underlying mechanisms of resistance and hold potential predictive value to inform treatment selection. We also describe how liquid biopsies for sampling of circulating markers and ultrasensitive detection technologies have emerged which complement ongoing efforts for biomarker discovery and analysis. Expert commentary:While evidence suggests that genomic aberrations in ER and HER2 could contribute to meeting the pressing need for better predictive biomarkers, efforts need to be made to standardise assessment methods and better understand the resistance mechanisms these markers denote. Taking advantage of emerging technologies, research in upcoming years should include prospective trials incorporating these predictors into the study design to validate their potential clinical value.

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“…Few studies have described how molecular features from different histological types may influence treatment response (Caldarella et al, 2013;Weigelt et al, 2008). Mucinous tumors are often described as Luminal A, and recent studies have shown that this subtype tended to have worse responses to cytotoxic agents and develop resistance to chemotherapy compared earlier to other histological subtypes (Araki & Miyoshi, 2018;Martelotto, Ng, Piscuoglio, Weigelt, & Reis-Filho, 2014).…”

Section: Introductionmentioning

confidence: 99%

Copy number alterations associated with clinical features in an underrepresented population with breast cancer

Peres

Carvalho

Anurag

et al. 2019

Molec Gen & Gen Med

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Background As the most incident tumor among women worldwide, breast cancer is a heterogeneous disease. Tremendous efforts have been made to understand how tumor characteristics as histological type, molecular subtype, and tumor microenvironment collectively influence disease diagnosis to treatment, which impact outcomes. Differences between populations and environmental and cultural factors have impacts on the origin and evolution of the disease, as well as the therapeutic challenges that arise due to these factors. We, then, compared copy number variations (CNVs) in mucinous and nonmucinous luminal breast tumors from a Brazilian cohort to investigate major CNV imbalances in mucinous tumors versus non‐mucinous luminal tumors, taking into account their clinical and pathological features. Methods 48 breast tumor samples and 48 matched control blood samples from Brazilian women were assessed for CNVs by chromosome microarray. Logistic regression and random forest models were used in order to assess CNVs in chromosomal regions from tumors. Results CNVs that were identified in chromosomes 1, 5, 8, 17, 19, and 21 classify tumors according to their histological type, ethnicity, disease stage, and familial history. Conclusion Copy number alterations described in this study provide a better understanding of the landscape of genomic aberrations in mucinous breast cancers that are associated with clinical features.

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Mechanism of resistance to endocrine therapy in breast cancer: the important role of PI3K/Akt/mTOR in estrogen receptor-positive, HER2-negative breast cancer

Cited by 142 publications

References 96 publications

Predictive markers of endocrine response in breast cancer

Predictive markers of endocrine response in breast cancer

The evolving role of receptors as predictive biomarkers for metastatic breast cancer

Copy number alterations associated with clinical features in an underrepresented population with breast cancer

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