title: Triple-negative breast cancer and poly(ADP-ribose) polymerase inhibitors.
abstract: Recent gene profiling studies have identified at least 5 major subtypes of breast cancer, including normal type, luminal A type, luminal B type, human epidermal growth factor receptor (HER)-2 positive type, and basal-like type. Triple-negative breast cancer (TNBC), showing no or low expressions of estrogen receptor (ER), progesterone receptor (PgR), and HER2, considered important clinical biomarkers, accounts for 10% to 20% of all breast cancers. Hormonal therapy and molecular targeted therapy are not indicated for the management of TNBC, resulting in poor outcomes. Because TNBC lacks clear-cut therapeutic targets, effective treatment strategies remain to be established. However, TNBC is known to share similar biologic characteristics with basal-like type breast cancer and is often accompanied by loss of functional BRCA, a gene-modifying enzyme. Breast cancer with BRCA1 or BRCA2 mutations is accompanied by activation of the enzyme poly(ADP-ribose) polymerase (PARP). PARP, a DNA base-excision repair enzyme, is known to play a central role in gene repair, along with BRCA. Because some breast cancers with BRCA1 or BRCA2 mutations are TNBC, the suppression of PARP has attracted attention as a new treatment strategy for TNBC. In this article, we review the clinical characteristics of TNBC, discuss problems in treatment, and briefly summarize the international development status of PARP inhibitors.
authors.affiliation: Breast Surgery, Sakura Medical Center, School of Medicine, Faculty of Medicine, Toho University, Japan. youngjinpark@sakura.med.toho-u.ac.jp
authors.forename: Youngjin
authors.initials: Y
authors.lastname: Park
authors.forename: Ayako
authors.initials: A
authors.lastname: Moriyama
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kitahara
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Tasuku
authors.initials: T
authors.lastname: Urita
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kato
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D019313:BRCA1 Protein / Q000172:deficiency / Q000235:genetics; D024682:BRCA2 Protein / Q000172:deficiency / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D005260:Female; D006801:Humans; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000172:deficiency / Q000235:genetics; D011960:Receptors, Estrogen / Q000172:deficiency / Q000235:genetics; D011980:Receptors, Progesterone / Q000172:deficiency / Q000235:genetics; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C492913:BRCA1 protein, human; C551750:BRCA2 protein, human; C508053:ERBB2 protein, human