title: Palbociclib for the treatment of postmenopausal breast cancer - an update.
abstract: BACKGROUND
  Breast cancer is a heterogeneous disease comprising different biological subtypes. In two thirds of tumours, expression of steroid-receptors is present, allowing for targeted treatment with endocrine therapy. In metastatic breast cancer, sequential administration of different non-cross resistant drugs offers a chance to delay cytotoxic chemotherapy. Activity of endocrine therapy, however, decreases with time as indicated by a shorter progression-free survival interval with every further treatment line, suggesting onset of resistance. Current research therefore focuses on prevention or delay of resistance by combining endocrine therapy with other targeted treatment approaches such as small-molecule pathway-inhibitors. Indeed, combining the steroidal aromatase-inhibitor exemestane with the mTor-inhibitor everolimus doubles activity of endocrine therapy in a pretreated population albeit at the price of increased toxicity. Data from several clinical trials suggest that inhibitors of the cycline-dependent kinases (CDK) 4 and 6 are able to delay or reverse resistance to endocrine therapy as well, while tolerability may be superior.
  
  
  METHODS
  This review provides a summary of clinical data on CDK 4/6 inhibitors, summarizes the biological rational for their use and provides an outlook to future developments in this field. A systematic literature search was performed in order to identify publications concerning the use of CDK 4/6 inhibitors in breast cancer. The search included original research articles, abstracts from major conferences and reviews published from 2005 to 2015 and was limited to English-language publications.
  
  
  CONCLUSIONS
  Based upon available data regarding activity and tolerability, it is believed that CDK 4/6 inhibitors will evolve to become a valuable addition to the therapeutic options in metastatic breast cancer.
authors.affiliation: a Department of Internal Medicine I/Division of Oncology , Medical University of Vienna , Vienna , Austria.|c Comprehensive Cancer Center Vienna , Vienna , Austria.
authors.forename: Guenther G
authors.initials: GG
authors.lastname: Steger
authors.affiliation: b Surgical Department , Medical University of Vienna , Vienna , Austria.|c Comprehensive Cancer Center Vienna , Vienna , Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Gnant
authors.affiliation: a Department of Internal Medicine I/Division of Oncology , Medical University of Vienna , Vienna , Austria.|c Comprehensive Cancer Center Vienna , Vienna , Austria.
authors.forename: Rupert
authors.initials: R
authors.lastname: Bartsch
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors*; D051361:Cyclin-Dependent Kinase 6 / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D010879:Piperazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017698:Postmenopause; D011725:Pyridines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D010879:Piperazines; D011725:Pyridines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C495911:CDK6 protein, human; C500026:palbociclib
keywords: Abemaciclib; CDK 4/6 inhibitors; breast cancer; cycline-dependent kinases 4 and 6; endocrine treatment; palbociclib; resistance; ribociclib