Epidemiology, biology, and treatment of triple-negative breast cancer in women of African ancestry

Abstract

Breast cancer incidence is increasing worldwide, and breast cancer-related mortality is highest in women of African ancestry, who are more likely to have basal-like or triple-negative breast cancer (TNBC) than are women of European ancestry. Identification of cultural, epidemiological, and genetic risk factors that predispose women of African ancestry to TNBC is an active area of research. Despite the aggressive behaviour of TNBC, achievement of a pathological complete response with chemotherapy is associated with good long-term survival outcomes, and sensitivity to chemotherapy does not seem to differ according to ethnic origin. Discovery of the molecular signalling molecules that define TNBC heterogeneity has led to the development of targeted agents such as inhibitors of poly (ADP-ribose) polymerase-1 and mTOR and immunomodulatory drugs that are in the early stages of clinical testing. First, we summarise the existing published work on the differences reported on the epidemiology, biology, and response to systemic treatment of TNBC between women of African ancestry and white women, and identify some gaps in knowledge. Second, we review the opportunities for development of new therapeutic agents in view of the potential high clinical relevance for patients with TNBC irrespective of race or ethnic origin.

Figure 1. Global breast cancer incidence and mortality in women in 2012

*Includes all regions of Europe, Northern America, Australia, New Zealand, and Japan. †Includes all regions of Africa, Asia (excluding Japan), Latin America, the Caribbean, Melanesia, Federated States of Micronesia, and Polynesia. Region definitions from IARC WHO. Data from the International Agency for Research on Cancer, GLOBOCAN 2012.

Figure 2. Overall survival after breast cancer surgery

Lines show survival as a function of response to chemotherapy (pathological complete response [pCR] vs residual disease [RD]) and triple-negative status (triple-negative breast cancer [TNBC] vs non-TNBC). Reproduced with permission from Liedtke and colleagues.

Figure 3. Oncogenic pathways associated with breast cancer

Selected genes and pathways differentially associated with specific breast cancer subtypes. Green arrows show activating signals. Red lines show inhibitory effects. Akt=akt proto-oncogene. AMPK=AMP-activated protein kinase. AR=androgen receptor. ARE=androgen response element. CDK=cyclin-dependent kinase. DSB=double-strand break. ER=oestrogen receptor. ERE=oestrogen response element. E2=oestrogen. IGFR=insulin-like growth factor receptor. IR=insulin receptor. MAPK=mitogen-activated protein kinase. MAPKK/MEK=mitogen-activated protein kinase kinase. P13K=phosphatidylinositol 3-kinase. PARP=poly ADP-ribose polymerase. pS6=ribosomal protein S6. pS6K=pS6 kinase. PTEN=phosphate and tensin homologue. Raf=raf-1 proto-oncogene. SRC=SRC proto-oncogene. TSC1=tuberous sclerosis 1. TSC2=tuberous sclerosis 2.