title: Challenges in the management of advanced, ER-positive, HER2-negative breast cancer.
abstract: Hormone-receptor-positive breast cancer accounts for the majority-up to 80%-of all breast cancers. The evolution of breast cancer from early stage to the metastatic setting leads to increased heterogeneity, the occurrence of new mutations, and the development of treatment resistance representing a great challenge for management decisions. Unfortunately, little data exist to offer guidance in this context, and a reliance on traditional clinical parameters remains when deciding on optimal treatment. In advanced-stage oestrogen receptor-positive (ER+) disease, ongoing issues include the choice between endocrine therapy and chemotherapy, the appropriate sequence of treatment agents, and the incorporation of biological agents, such as everolimus, into the treatment armamentarium. In metastatic disease, repeated biopsies can help to reassess the receptor or genetic mutational status; however, the evidence to support this approach is limited. In this Review, we examine the current evidence that can guide treatment decisions in patients with advanced-stage ER+ breast cancer, discuss how to tackle these therapeutic challenges and provide suggestions for the optimal management of this patient population.
authors.affiliation: 'Sandro Pitigliani' Medical Oncology Unit, Hospital of Prato, Instituto Toscano Tumori, Via Suor Niccolina 20, Prato, PO 59100, Italy.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Hart
authors.affiliation: Translational Research Laboratory, Hospital of Prato, Instituto Toscano Tumori, Via Suor Niccolina 20, Prato, PO 59100, Italy.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Migliaccio
authors.affiliation: Translational Research Laboratory, Hospital of Prato, Instituto Toscano Tumori, Via Suor Niccolina 20, Prato, PO 59100, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Malorni
authors.affiliation: Translational Research Laboratory, Hospital of Prato, Instituto Toscano Tumori, Via Suor Niccolina 20, Prato, PO 59100, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Guarducci
authors.affiliation: 'Sandro Pitigliani' Medical Oncology Unit, Hospital of Prato, Instituto Toscano Tumori, Via Suor Niccolina 20, Prato, PO 59100, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Biganzoli
authors.affiliation: 'Sandro Pitigliani' Medical Oncology Unit, Hospital of Prato, Instituto Toscano Tumori, Via Suor Niccolina 20, Prato, PO 59100, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Di Leo
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen