Current status and future perspectives for the treatment of triple-negative breast cancer in Japan]

Triple-negative breast cancer (TNBC) is negative for all three markers, namely the hormone sensitivity receptors: estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). TNBC accounts for approximately 15% of all primary breast cancer cases. In general, patients with this disease have a higher risk of recurrence and a poorer prognosis compared with those with other subtypes of breast cancer. Patients with TNBC are defined as those for whom endocrine or anti-HER2 therapy are not indicated due to poor response. It is a heterogeneous disease group that shows various characteristics. There is a group that achieves a complete response to chemotherapy and has an excellent prognosis, a group that does not respond to chemotherapy and has a poor prognosis, and a group that has an excellent inherent prognosis and does not need chemotherapy. The subdivision of TNBC cases based on the prognosis and response to therapy is an issue for the future. In addition to classifying TNBC into basal and non-basal types by testing cytokeratin 5/6 (CK5/6) and epidemic growth factor receptors (EGFR) by the immunohistochemical staining method, Ki-67 may predict sensitivity to anticancer agents and a change in Ki-67 before and after therapy may potentially predict prognosis. Patients with a non-pathologic complete response (non-pCR) to preoperative chemotherapy have a high risk of early recurrence, and measures to deal with it are therefore needed. At present, the most commonly used perioperative chemotherapy is sequential combination therapy of an anthracycline drug and a taxane drug; however, it is limited because the pathologic complete response(pCR)rates following preoperative chemotherapy range from 30 to 40%. There is also an urgent need to develop a regimen that will overcome this problem. In association with BRCA gene mutations, sensitivity to DNA-damaging anticancer agents may lead to promising therapies. However, unfortunately, the use of DNA-damaging agents such as cisplatin and carboplatin is not covered by health insurance in Japan. Various new molecular targeted drugs aimed at blocking cell proliferation factors are expected to be developed in the future. Here we have summarized the current status and issues based on the clinical experience with the diagnosis and treatment of TNBC.