scholarly journals Therapy after cyclin‐dependent kinase inhibition in metastatic hormone receptor‐positive breast cancer: Resistance mechanisms and novel treatment strategies

Cancer ◽  
2020 ◽  
Vol 126 (15) ◽  
pp. 3400-3416 ◽  
Author(s):  
Marina N. Sharifi ◽  
Apoorva Anandan ◽  
Patrick Grogan ◽  
Ruth M. O’Regan
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Treatment Strategies ◽  
Resistance Mechanisms ◽  
Cyclin Dependent Kinase ◽  
Cancer Resistance ◽  
Hormone Receptor Positive ◽  
Novel Treatment ◽  
Novel Treatment Strategies ◽  
Positive Breast Cancer

Review of Cyclin-Dependent Kinase 4/6 Inhibitors for the Treatment of Hormone Receptor–Positive Advanced Breast Cancer

2018 ◽  
Vol 53 (2) ◽  
pp. 195-203
Author(s):  
Keith A. Hecht ◽  
Christopher Selby
Keyword(s):  
Breast Cancer ◽  
Adverse Effects ◽  
Advanced Breast Cancer ◽  
Hormone Receptor ◽  
Progression Free Survival ◽  
Advanced Breast ◽  
Cdk Inhibitors ◽  
Cyclin Dependent Kinase ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

Objective: To evaluate the existing literature regarding the use of cyclin-dependent kinase (CDK) 4/6 inhibitors in the treatment of hormone receptor–positive advanced breast cancer (ABC). Data Sources: A search of the medical literature was performed using PubMed (2014 to June 2018). Search terms included cyclin-dependent kinase, CDK, breast cancer, palbociclib, ribociclib, abemaciclib, PD0332991, LEE011, and LY2835219. Clinicaltrials.gov was also searched. Study Selection and Data Extraction: Trials with clinical efficacy outcomes evaluating CDK 4/6 inhibitors in the treatment of advanced hormone-positive breast cancer were considered. Data Synthesis: Palbociclib, abemaciclib, and ribociclib each demonstrated significant benefit when combined with an aromatase inhibitor, the benefit to patients was similar for each, with an improvement of 42% to 51% in median progression-free survival (PFS). In combination with fulvestrant, CDK 4/6 inhibitors used for the treatment of hormone receptor–positive ABC resulted in a 43% to 58% improvement in median PFS versus fulvestrant alone. CDK inhibitors are relatively well tolerated; however, discontinuation as a result of adverse effects was highest with abemaciclib. Relevance to Patient Care and Clinical Practice: This review considers the use of the 3 commercially available CDK 4/6 inhibitors for treatment of hormone receptor–positive breast cancer, including data on each of the 3 agents in newly advanced and treatment refractory disease. Conclusions: The CDK inhibitors should be used in combination with endocrine therapies for the treatment of ABC. Efficacy of the 3 agents is similar. Selection within the class should include consideration of adverse effects and drug interactions.

Cyclin-Dependent Kinase 4/6 Inhibitors in Neoadjuvant Endocrine Therapy of Hormone Receptor-Positive Breast Cancer

2019 ◽  
Vol 19 (6) ◽  
pp. 392-398 ◽  
Author(s):  
Lorenzo Rossi ◽  
Amelia McCartney ◽  
Emanuela Risi ◽  
Irene De Santo ◽  
Ilenia Migliaccio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Hormone Receptor ◽  
Cyclin Dependent Kinase ◽  
Neoadjuvant Endocrine Therapy ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

scholarly journals CDK4/6 Inhibitors in Hormone Receptor-Positive Metastatic Breast Cancer: Current Practice and Knowledge

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2480
Author(s):  
Debora de Melo Gagliato ◽  
Antonio C Buzaid ◽  
Jose Manuel Perez-Garcia ◽  
Antonio Llombart ◽  
Javier Cortes
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Hormone Receptor ◽  
Current Knowledge ◽  
Metastatic Breast ◽  
Endocrine Treatment ◽  
Cyclin Dependent Kinase ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

Treatment paradigms in advanced hormone receptor (HR)-positive breast cancer were substantially transformed with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) approval. The addition of these drugs to endocrine treatment profoundly improved progression-free and overall survival. Additionally, other important endpoints, such as the response rate, time to chemotherapy, and a delay in quality of life deterioration, were positively impacted by CDK4/6 inhibitors’ addition to the treatment of advanced HR-positive breast cancer. This review article will summarize current knowledge on CDK4/6 inhibitors in clinical practice for advanced HR-positive metastatic breast cancer, as well as describe recent efforts to more precisely characterize mechanisms of sensitivity and resistance to these drugs, both on the molecular and clinical characterization level.

Cyclin-dependent kinase 4 and 6 inhibitors for hormone receptor-positive breast cancer: past, present, and future

The Lancet ◽  
2020 ◽  
Vol 395 (10226) ◽  
pp. 817-827 ◽  
Author(s):  
Laura M Spring ◽  
Seth A Wander ◽  
Fabrice Andre ◽  
Beverly Moy ◽  
Nicholas C Turner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Cyclin Dependent Kinase ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

scholarly journals Endocrine Treatment for Breast Cancer Patients Revisited—History, Standard of Care, and Possibilities of Improvement

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5643
Author(s):  
Naiba Nabieva ◽  
Peter A. Fasching
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Hormone Receptor ◽  
Standard Of Care ◽  
Resistance Mechanisms ◽  
Endocrine Treatment ◽  
Breast Cancer Patients ◽  
Current Standard ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

Purpose of review: Due to the findings of current studies and the approval of novel substances for the therapy of hormone-receptor-positive breast cancer patients, the established standards of endocrine treatment are changing. The purpose of this review is to give an overview of the history of endocrine treatment, to clarify its role in the present standard of care, and to discuss the possibilities of improvement. Recent findings: Tamoxifen, aromatase inhibitors, and fulvestrant are the main drugs that have been used for decades in the therapy of hormone-receptor-positive breast cancer patients. However, since a relevant number of women suffer at some point from disease recurrence or progression, several novel substances are being investigated to overcome resistance mechanisms by interfering with certain signaling pathways, such as the PI3K/AKT/mTOR or the CDK4/6 pathways. mTOR and CDK4/6 inhibitors were the first drugs approved for this purpose and many more are in development. Summary: Endocrine treatment is one of the best tolerable cancer therapies available. Continuous investigation serves to improve patients’ outcomes and modernize the current standard of care. Considering the resistance mechanisms and substances analyzed against these, endocrine treatment of hormone-receptor-positive breast cancer is on the brink of a new era.

Aromatase inhibitors and breast cancer

2012 ◽  
Vol 9 (2) ◽  
Author(s):  
Saranya Chumsri ◽  
Angela Brodie
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Aromatase Inhibitors ◽  
Hormone Receptor ◽  
Breast Cancer Treatment ◽  
Cancer Resistance ◽  
Hormone Receptor Positive ◽  
Metastatic Setting ◽  
Increased Risk ◽  
Positive Breast Cancer

AbstractBreast cancer is the most prevalent cancer and the second leading cause of death among women worldwide. The advent of hormonal therapy has revolutionized the treatment for breast cancer for a century. In the 1960s, an important advance was the development of the antiestrogen tamoxifen. While this drug has had a major impact on breast cancer treatment, its partial agonist activity is associated with increased risk of stroke and endometrial cancer as well as drug resistance. One of the breakthroughs in breast cancer treatment is the discovery of aromatase inhibitors (AIs) in the early 1970s. AIs have proven to be effective in treating hormone receptor-positive breast cancer and lack the estrogenic effects of tamoxifen. They are now considered to be the standard treatment for postmenopausal women with hormone receptor-positive breast cancer. While AIs are effective in treating hormone receptor-positive breast cancer, resistance to AIs inevitably occurs in metastatic setting after prolonged suppression of estrogen production. This chapter summarizes the evolution of AIs, clinical efficacy of AIs, mechanisms of AI resistance, and the strategies to overcome resistance.

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