Advances in Endocrine-Based Therapies for Estrogen Receptor-Positive Metastatic Breast Cancer

AbstractApproximately 70% of breast cancers are estrogen-receptor positive. Tamoxifen and aromatase inhibitors have been the mainstay of endocrine therapy and have improved breast cancer survival. However, a large number of patients experience disease recurrence either during or following completion of endocrine therapy. Recent improvements in our understanding of the various mechanisms underlying the development of endocrine resistance have led to a dramatic change in the landscape of current endocrine treatment with the introduction of new drugs targeting molecular pathways involved in endocrine resistance. Over the past years we have witnessed the use of combination endocrine therapy with mammalian target of rapamycin antagonists, whilst most recently the introduction of cyclin-dependent kinase 4/6 inhibitors has significantly improved response to endocrine therapy. Whilst not a formal systematic review, this article will provide historical background and summarise key clinical trials and current strategies in both first-line and second-line endocrine therapy.
Source: Drugs - Category: Drugs & Pharmacology Source Type: research

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In this study, the correlation between ZBTB7A and ER-α was confirmed by tissue microarray-based and TCGA database. Then, we explore if ZBTB7A maintains ER-α’s level via targeting ER-α’s expression or degradation. Finally, we examined the effect of ZBTB7A on the proliferation of breast cancer cells.Key findingsWe further confirmed that ZBTB7A shows a significant positive correlation with ER-α in clinical breast cancer samples by tissue microarray-based analysis. Mechanically, we identified that the inhibition of ZBTB7A could upregulate E3 ligase TRIM25 leading to enhancement of ER-α...
Source: Life Sciences - Category: Biology Source Type: research
Authors: Guo K, Feng G, Yan Q, Sun L, Zhang K, Shen F, Shen M, Ruan S Abstract CXC chemokine receptors (CXCRs) and chemokines are involved in tissue development and homeostasis, including in cancer development and progression. To date, seven CXCRs have been identified. However, the expression of CXCRs and their influence on the occurrence and development of breast cancer (BC) requires further investigation. In the present study, mRNA expression levels of the seven CXCRs were compared between normal tissues and several cancer types using the Oncomine database. Highly expressed CXCRs were selected and the expression ...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
Publication date: Available online 24 October 2019Source: The Journal of Molecular DiagnosticsAuthor(s): André Franken, Ellen Honisch, Florian Reinhardt, Franziska Meier-Stiegen, Liwen Yang, Sandra Jaschinski, Irene Esposito, Barbara Alberter, Bernhard Polzer, Hanna Huebner, Peter A. Fasching, Sunil Pancholi, Lesley-Ann Martin, Eugen Ruckhaeberle, Fabienne Schochter, Marie Tzschaschel, Andreas D. Hartkopf, Volkmar Mueller, Dieter Niederacher, Tanja FehmMutations in the ligand-binding domain (LBD) of the ESR1 gene result in resistance to estrogen deprivation therapy (EDT) in breast cancer. Their detection might enabl...
Source: The Journal of Molecular Diagnostics - Category: Pathology Source Type: research
Condition:   Cancer Metastatic Interventions:   Drug: Paclitaxel injection;   Drug: Capecitabine tablets;   Drug: Letrozole 2.5mg;   Drug: Anastrozole 1mg;   Drug: Fulvestrant Prefilled Syringe;   Drug: Abemaciclib Sponsor:   UNICANCER Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conclusions: Despite encouraging pre-clinical evidence, there is a lack of clinical data to inform CNS-specific response rates to CDK4/6 inhibitors among patients with metastatic breast cancer. Given that the treatment of patients with breast cancer brain metastases represents an area of unmet medical need, enrollment of patients with CNS metastases in ongoing clinical trials should be encouraged; innovative trials that examine response of CNS metastases to CDK4/6 inhibitors are also of interest. PMID: 31695840 [PubMed]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
In conclusion, PLB exerted anti-cancer activity and eliminated stem-like properties by attenuating Wnt/β-catenin signaling and FGF2 expression. These findings suggest that PLB could be a promising agent to treat endocrine resistant breast cancer.Graphical abstract
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
A new study shows that almost all postmenopausal women taking endocrine therapy to prevent breast cancer relapses report adverse effects on sexual function.Medscape Medical News
Source: Medscape Hematology-Oncology Headlines - Category: Cancer & Oncology Tags: Hematology-Oncology News Source Type: news
Conclusion: CDK4/6 inhibitors are highly specific making them a safe and viable therapeutic for BC and there is increasing evidence of their potential to improve survival, even in the metastatic setting. Although a number of trials have demonstrated this, as a lone therapy or in combination, optimisation of treatment scheduling are still required in further clinical investigations. PMID: 31671026 [PubMed - as supplied by publisher]
Source: Acta Oncologica - Category: Cancer & Oncology Authors: Tags: Acta Oncol Source Type: research
Authors: Heitz F, Kümmel S, Lederer B, Solbach C, Engels K, Ataseven B, Sinn B, Blohmer JU, Denkert C, Barinoff J, Fisseler-Eckhoff A, Loibl S Abstract Introduction Oestrogen receptor beta (ER-β) is abundantly expressed in breast cancer (BC), but its impact on neoadjuvant chemotherapy outcome is unknown. Patients and Methods Patients treated in the neoadjuvant GeparTrio trial with available tissue for immunohistochemical analyses were included. Nuclear ER-β expression was correlated with clinico-pathologic characteristics. The impact of its expression on pathological complete response (pCR [ypT0/ypN0...
Source: Geburtshilfe und Frauenheilkunde - Category: OBGYN Tags: Geburtshilfe Frauenheilkd Source Type: research
In this study, we investigated the prognostic and predictive role of CDC20 in early ER+ breast cancer patients.MethodsThe biological and clinical impact of CDC20 expression was assessed in large clinical annotated cohort of ER+  breast cancer with long-term follow-up at the mRNA level, using METABRIC and KM-Plotter datasets, and the protein level using immunohistochemistry on patients presenting at Nottingham. CDC20 expression was correlated with clinico-pathological parameters, molecular subtypes, clinical outcome and e fficacy of endocrine therapy.ResultsHigh CDC20 mRNA expression was associated with poor c...
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
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