title: Endocrine treatment in breast cancer: Cure, resistance and beyond.
abstract: Hormone receptor positive breast cancer (HR-positive BC) is the most frequent BC subtype (∼70%), with endocrine treatment constituting its therapeutic cornerstone; despite its efficacy, endocrine resistance can develop, clinically as a relapse or a progression of the early or advanced disease respectively, hence necessitating alternative treatments. Over the last two decades, improved understanding of the molecular mechanisms of endocrine resistance has been achieved, with numerous targeted agents undergoing clinical development. Despite the multifactorial genesis of endocrine resistance, fuelled not only by alternative oncogenic signaling pathways of tumor cells, but also by tumor microenvironment-mediated mechanisms, successful clinical development of new agents has been recently noted. However, predictive biomarkers for accurate 'navigation' across the different treatment options are urgently needed. In this article, we present a thorough overview of the different clinical scenarios of BC endocrine resistance, and the recent advances in endocrine treatment, we describe the basic molecular mediators of endocrine resistance and the respective targeted agents undergoing clinical development; finally, we provide our perspective on the future of BC endocrine treatment.
authors.affiliation: European Organization for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tryfonidis
authors.affiliation: Breast International Group (BIG), Brussels, Belgium.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Zardavas
authors.affiliation: University of Illinois and College of Medicine, Department of Molecular and Integrative Physiology, IL, USA.
authors.forename: Benita S
authors.initials: BS
authors.lastname: Katzenellenbogen
authors.affiliation: Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: martine.piccart@bordet.be.
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
mesh_terms: D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068338:Everolimus / Q000008:administration & dosage; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D058990:Molecular Targeted Therapy; D020360:Neoadjuvant Therapy; D010879:Piperazines / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D010879:Piperazines; D011725:Pyridines; D011960:Receptors, Estrogen; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol; D000068338:Everolimus; C500026:palbociclib; C056516:exemestane
keywords: Endocrine treatment; Molecular mechanisms; New agents; Resistance