Abstract
Despite advances in the treatment of hormone receptor-positive, HER2- metastatic breast cancer, the disease is rarely curable. In this review, we focus on the use of CDK4/6 inhibitors, examining clinical experience and the mechanisms underlying the development of resistance, and evaluating treatment options after failure to respond to CDK4/6 inhibitors. Current basic research supports the use of mammalian target of rapamycin inhibitors after CDK4/6 inhibitor failure; however, more data are needed, particularly regarding treatment sequencing. Real-world data studies may help to fill the current knowledge gap, particularly where large-scale randomized controlled studies are not feasible.
Keywords:
CDK4/6 inhibitors; HR+ HER2- metastatic breast cancer; best practice; mTOR inhibitors; real-world data; resistance; treatment sequencing.
MeSH terms
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Biomarkers, Tumor / metabolism*
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Breast Neoplasms / etiology
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Breast Neoplasms / mortality
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Breast Neoplasms / pathology
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Breast Neoplasms / therapy*
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Cyclin-Dependent Kinase 4 / antagonists & inhibitors
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Cyclin-Dependent Kinase 6 / antagonists & inhibitors
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Disease Management
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Drug Resistance, Neoplasm / drug effects
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Drug Resistance, Neoplasm / genetics
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Female
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Humans
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Japan
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Neoplasm Staging
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Phosphatidylinositol 3-Kinases / metabolism
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Postmenopause
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use
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Proto-Oncogene Proteins c-akt / metabolism
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Receptor, ErbB-2 / metabolism
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Receptors, Estrogen / metabolism
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Receptors, Progesterone / metabolism
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Retreatment
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Signal Transduction
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TOR Serine-Threonine Kinases / metabolism
Substances
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Biomarkers, Tumor
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Protein Kinase Inhibitors
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Receptors, Estrogen
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Receptors, Progesterone
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Receptor, ErbB-2
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinase 6