Title:Triple-negative Breast Cancer and Poly(ADP-ribose) Polymerase Inhibitors
VOLUME: 12 ISSUE: 6
Author(s):Youngjin Park, Ayako Moriyama, Tomoaki Kitahara, Yutaka Yoshida, Tasuku Urita and Ryoji Kato
Affiliation:Breast Surgery, Sakura Medical Center, School of Medicine, Faculty of Medicine, Toho University, Japan.
Keywords:BRCA, Breast cancer, DNA base-excision repair, PARP, PARP inhibitors, Triple-negative breast cancer
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.
