Triple-negative breast cancer: future prospects in diagnosis and management

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype comprising about 10-20 % of breast cancer patients with an overall poor prognosis. Recently, it was found to be a heterogeneous disease that has been classified into six subtypes based on molecular signature. In preclinical trials, these subtypes have different active signaling pathways with variable response to chemotherapy. To improve treatment outcome of TNBC, therapy should be tailored according to the active driving signaling aberration. Molecular testing represents the optimal way to stratify patients, but it has some difficulties to be implemented in routine clinical practice. This article provides an assumption for stepped diagnostic algorithm of TNBC based on immunohistochemistry markers in addition to a suggested tailored therapeutic strategy for advanced TNBC based on the driving aberrations. Furthermore, most TNBC patients develop early relapse despite adjuvant chemotherapy. We provide a design for future adjuvant therapy for the disease. This design is based on targeting proposed active pathways in breast cancer stem cells responsible for regenerating the tumor and disease relapse. Finally, we provide a proposed design for future clinical trials in TNBC to allow for investigation of different medications in this heterogeneous disease based on upfront patient stratification and then allocation to the suitable treatment arms.