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

Check-point inhibitors have erupted as a treatment option for numerous kinds of neoplasms. Although there have been some achievements, the evidence supporting their use in breast cancer is scarce. Combinations with chemotherapy seem to provide better outcomes, and triple negative is the subtype most likely to benefit from them. New combination strategies are undergoing research to improve these results. Other approaches to determining biomarkers that identify which populations clearly benefit from these therapies are needed. Here, we review the clinical data of the role of immune check-point inhibitors in early and advanced breast cancer and present emerging strategies.

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The role of abemaciclib in treatment of advanced breast cancer

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835918776925 ◽

2018 ◽

Vol 10 ◽

pp. 175883591877692 ◽

Cited By ~ 5

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.

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Novel Strategies in Hormone Receptor-Positive Advanced Breast Cancer: Overcoming Endocrine Resistance

Current Breast Cancer Reports ◽

10.1007/s12609-016-0228-1 ◽

2016 ◽

Vol 8 (4) ◽

pp. 193-205 ◽

Cited By ~ 2

Author(s):

A. C. Garrido-Castro ◽

O. Metzger-Filho

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Hormone Receptor ◽

Endocrine Resistance ◽

Advanced Breast ◽

Hormone Receptor Positive

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Endocrine Resistance in Advanced Breast Cancer

Acta Oncologica ◽

10.3109/02841869609083979 ◽

1996 ◽

Vol 35 (sup5) ◽

pp. 91-95 ◽

Cited By ~ 14

Author(s):

Mitchell Dowsett

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Endocrine Resistance ◽

Advanced Breast

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

The Journal of Applied Laboratory Medicine ◽

10.1093/jalm/jfaa117 ◽

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.

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