title: Targeted therapies for ER+/HER2- metastatic breast cancer.
abstract: The majority of breast cancers present with estrogen receptor (ER)-positive and human epidermal growth factor receptor (HER2)-negative features and might benefit from endocrine therapy. Although endocrine therapy has notably evolved during the last decades, the invariable appearance of endocrine resistance, either primary or secondary, remains an important issue in this type of tumor. The improvement of our understanding of the cancer genome has identified some promising targets that might be responsible or linked to endocrine resistance, including alterations affecting main signaling pathways like PI3K/Akt/mTOR and CCND1/CDK4-6 as well as the identification of new ESR1 somatic mutations, leading to an array of new targeted therapies that might circumvent or prevent endocrine resistance. In this review, we have summarized the main targeted therapies that are currently being tested in ER+ breast cancer, the rationale behind them, and the new agents and combinational treatments to come.
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. mibusuki@kumamoto-u.ac.jp.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Yamamoto-Ibusuki
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France. monica.arnedos@gustaveroussy.fr.|INSERM Unit U981, Gustave Roussy Cancer Campus, Villejuif, France. monica.arnedos@gustaveroussy.fr.
authors.forename: Monica
authors.initials: M
authors.lastname: Arnedos
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France. fabrice.andre@gustaveroussy.fr.|INSERM Unit U981, Gustave Roussy Cancer Campus, Villejuif, France. fabrice.andre@gustaveroussy.fr.|Department of Medical Oncology and INSERM Unit U981, Gustave Roussy Cancer Campus, 114 Rue Edouard Vaillant, Villejuif, 94800, France. fabrice.andre@gustaveroussy.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: André
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D011960:Receptors, Estrogen
chemical_list: D000970:Antineoplastic Agents; D011960:Receptors, Estrogen