scholarly journals Novel Agents Show Promise Against Acquired Endocrine Resistance in ER + Advanced Breast Cancer

2021 ◽  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Endocrine Resistance ◽  
Advanced Breast ◽  
Novel Agents

scholarly journals The role of abemaciclib in treatment of advanced breast cancer

2018 ◽  
Vol 10 ◽  
pp. 175883591877692 ◽  
Author(s):  
Amelia McCartney ◽  
Erica Moretti ◽  
Giuseppina Sanna ◽  
Marta Pestrin ◽  
Emanuela Risi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Single Agent ◽  
Endocrine Resistance ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Advanced Breast ◽  
Significant Activity ◽  
Epidermal Growth

Until recently, the mainstay of treatment in the majority of hormone receptor (HR)-positive, human epidermal growth factor 2 receptor (HER2)-negative advanced breast cancer (ABC) has consisted of single-agent endocrine therapy (ET). However, as understanding of endocrine resistance has grown, newer targeted agents have come to the fore. Inhibition of cyclin-dependent kinase complexes 4 and 6 (CDK4/6) combined with ET has shown significant activity in HR+ HER2− ABC, with impressive results in terms of progression-free survival (PFS) when compared with ET alone. This review summarizes the seminal findings pertaining to CDK4/6 inhibition in this population, specifically focusing on abemaciclib, contrasted with palbociclib and ribociclib. Potential directions for future studies are discussed, as a way of addressing outstanding issues such as establishing optimal treatment sequencing and agent combinations, appropriate patient selection to derive maximal benefits, predictive biomarkers and the employment of CDK4/6 inhibition beyond the ABC setting.

Endocrine Resistance in Advanced Breast Cancer

1996 ◽  
Vol 35 (sup5) ◽  
pp. 91-95 ◽  
Author(s):  
Mitchell Dowsett
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Endocrine Resistance ◽  
Advanced Breast

Plasma PIK3CA Mutation Testing in Advanced Breast Cancer Patients for Personalized Medicine: A Value Proposition

2020 ◽  
Vol 5 (5) ◽  
pp. 1076-1089
Author(s):  
Andrea Ferreira-Gonzalez
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Cancer Patients ◽  
Pik3ca Mutation ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Value Proposition ◽  
Breast Cancer Patients ◽  
A Value

Abstract Background Even though endocrine therapy is often initially successful in treating advanced breast cancer, most patients inevitably face disease progression. In advanced hormone receptor–positive (HR+) breast cancer, activation of the PI3K downstream pathway is a critical feature of the mechanism of endocrine resistance. A significant recent advance in treating HR+ advanced breast cancer has been the recent introduction of PI3K inhibitor (PI3Ki) for the treatment of patients with HR+, HER2-negative (HER2−) advanced or metastatic breast cancer that harbors PIK3CA mutations. A value proposition concept was applied to assess the potential benefits of cell-free tumor DNA (ctDNA) testing to identify patients who might respond to PI3Ki treatment. Content By applying the framework of the value proposition to >35 publications, in addition to recommendations from professional organizations, it was evident that robust clinical evidence exists to support the role of ctDNA PIK3CA mutation evaluation in identifying patients with advanced breast cancer who could benefit from PI3Ki treatment. Summary Detection of PIK3CA gene mutations in HR+HER2− advanced breast cancer patients allows for the identification of patients who might benefit from more effective personalized treatment with molecularly targeted drugs.

Saying goodbye to primary endocrine resistance for advanced breast cancer?

2021 ◽  
Vol 38 (1) ◽  
Author(s):  
Cengiz Karacin ◽  
Yakup Ergun ◽  
Omur Berna Oksuzoglu
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Endocrine Resistance ◽  
Advanced Breast

Endocrine resistance in advanced breast cancer: current evidence and future directions

2012 ◽  
Vol 1 (4) ◽  
pp. 305-314 ◽  
Author(s):  
Carlos H Barrios ◽  
André P Fay ◽  
Marcio Debiasi ◽  
Gustavo Werutsky
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Endocrine Resistance ◽  
Advanced Breast ◽  
Current Evidence ◽  
Future Directions

scholarly journals EMERALD: Phase III trial of elacestrant (RAD1901) vs endocrine therapy for previously treated ER+ advanced breast cancer

2019 ◽  
Vol 15 (28) ◽  
pp. 3209-3218 ◽  
Author(s):  
Aditya Bardia ◽  
Philippe Aftimos ◽  
Teeru Bihani ◽  
Alfred T Anderson-Villaluz ◽  
JungAh Jung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Advanced Breast Cancer ◽  
Endocrine Resistance ◽  
Progression Free Survival ◽  
Advanced Breast ◽  
Phase Iii ◽  
Open Label ◽  
Er Positive ◽  
Previously Treated

Elacestrant is a novel, nonsteroidal, orally bioavailable selective estrogen receptor degrader (SERD) that has demonstrated activity in patients with estrogen receptor (ER)-positive/HER2-negative breast cancer previously treated with endocrine therapies including fulvestrant and/or CDK 4/6 inhibitor therapy, and in those with ESR1 mutations ( ESR1-mut) known to confer endocrine resistance. Herein, we describe the design and methodology of EMERALD, an international, multicenter, randomized, open-label, active-controlled, Phase III clinical study comparing the efficacy and safety of elacestrant to standard-of-care endocrine monotherapy treatment (fulvestrant or an aromatase inhibitor, per investigator’s choice) in patients with ER-positive/HER2-negative advanced breast cancer. Primary end points are progression-free survival in ESR1-mut patients and in all patients (NCT03778931; EudraCT 2018-002990-24).

Monitoring of PIK3CA and ESR1 mutations in circulating tumor DNA as predictive and prognostic biomarkers in patients with endocrine-resistant ER+/HER2- advanced breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13045-e13045
Author(s):  
Jesús Fuentes Antrás ◽  
Vanesa García-Barberán ◽  
Irene Gonzalo ◽  
Fernando Moreno ◽  
Igor López-Cade ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Endocrine Therapy ◽  
Aromatase Inhibitors ◽  
Endocrine Resistance ◽  
Advanced Breast ◽  
Primary Tumors ◽  
Mutational Status ◽  
Esr1 Mutations

e13045 Background: Combination therapeutic strategies including CDK4/6 inhibitors and an endocrine backbone are the standard of care of treatment for patients with estrogen receptor positive (ER+)/HER2- advanced breast cancer (ABC). Endocrine agents mainly include aromatase inhibitors, which target ER-driven transcription, and fulvestrant, which functions as ER antagonist. PI3K-AKT-mTOR is a key point of resistance to endocrine therapy, activated in 40% of these patients by mutations concentrated in critical regions of PIK3CA, coding for the p110 catalytic subunit α of PI3K. Additionally, 30% of patients previously exposed to non-steroidal aromatase inhibitors develop mutations in the ligand binding domain of ESR1, causing endocrine resistance by constitutive activation of the ER. Furthermore, metastasis and primary tumors may show a highly heterogenous mutational landscape. Monitoring the dynamic changes of these mutations in ctDNA may provide a non-invasive, real-time and accessible tool to convey predictive/prognostic information and guide decisions on sequential endocrine therapies. Methods: Pre-planned interim analysis results of an observational, prospective cohort pilot study to assess the predictive and prognostic value of monitoring PIK3CA and ESR1 mutations in ctDNA of patients with endocrine-resistant ER+/HER2- ABC. We have studied longitudinal liquid biopsies from 30 patients using digital PCR to interrogate PIK3CA mutations (H1047R / E545K) and ESR1 mutations (D538G / Y537S). Blood samples were drawn at the time of progression to endocrine therapy, at 8 weeks of subsequent endocrine line and at new progression. This exploratory analysis will provide preliminary data on clinical homogeneity, treatment regimens, median follow-up and progression-free survival, mutation incidence and intraindividual variation of mutant allele frequency and copy number. The percentage of progressors at 24 weeks of follow-up according to the mutational status will be evaluated by using the Fisher’s exact test. The predictive potential of ctDNA biomarkers will be characterized by ROC curve analysis. Tracking ctDNA mutations to predict endocrine resistance in a real-world setting represents a critical step towards precision medicine in oncology.

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