Metastatic triple negative breast cancer: Optimizing treatment options, new and emerging targeted therapies

Abstract

Triple negative breast cancer (TNBC) is a heterogeneous disease, not only on the molecular level, but also on the pathologic and clinical levels. It also has a distinct epidemiology. TNBCs are frequently of high histologic grade, typically more aggressive and difficult to treat than hormone receptor-positive tumors, and they are associated with a higher risk of early relapse with visceral metastasis after surgery, chemotherapy and/or radiotherapy. The lack of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expression precludes the use of targeted therapies in advanced stages, and the only approved systemic treatment option is chemotherapy with or without bevacizumab. In patients with advanced TNBC, responses to chemotherapy occur, but are often of short duration and it is associated with poor prognosis. The median overall survival for patients with metastatic TNBC is about 9-12 months with conventional cytotoxic agents. Given the suboptimal outcomes with chemotherapy, new targeted therapies for TNBC are urgently needed. This review summarizes the clinical efficacy, perspectives and future challenges of using new treatment options for metastatic TNBC, such as poly-ADPribose-polymerase inhibitors, antiandrogen therapies and immune checkpoint inhibitors (antiprogrammed death receptor-1/PD-L1 monoclonal antibodies).

Dancing from bottoms up – Roles of the POZ-ZF transcription factor Kaiso in Cancer

“…The high BC mortality rates in women of African ancestry (WAA) despite having lower incidence rates and lifetime risks of BC than Caucasian women, initially led many to think that this disparity was linked to socio-economic status [93–97]. However, several studies now suggest that genetic risk factors/predisposition contribute to the racial disparity in the prevalence and mortality of patients diagnosed with the TNBC subtype [95, 97, 98]. Hence, the recent discovery that high Kaiso expression correlates with aggressive BC subtypes like TNBC and shorter metastasis-free survival in WAA [13, 81], as well as with aggressive PCa in African American (AA) men [14] suggests that high Kaiso expression may be linked to the racial disparity in prevalence and/or outcomes of aggressive cancers in people of African ancestry.…”

Oncolytic vesicular stomatitis virus–based cellular vaccine improves triple-negative breast cancer outcome by enhancing natural killer and CD8+T-cell functionality

“…However, TNBC is best considered as an umbrella term, encompassing a wide spectrum of entities with distinct genetic, transcriptional, histological and clinical differences. [1][2][3] As a group, TNBC is associated with high proliferation, early recurrence and poor survival rates. 2 4 This aggressive disease is resistant to widely used targeted therapies such as trastuzumab and endocrine therapies, which have been effective at reducing breast cancer mortality.…”

“…2 5 There are very limited and often ineffective treatment options for patients with poor prognosis (chemoresistant and late-stage/metastatic) TNBC. 2 Recent large-scale gene expression profiling and immunohistochemistry (IHC) analyses reveal that TNBC may be the most regulated by tumor-infiltrating lymphocytes (TILs) and thus the most responsive to immunotherapies compared with other breast cancer subtypes. 6 7 In addition, accumulating data suggest that certain chemotherapeutic drugs such as anthracyclines mediate their anti-cancer activity through direct cytotoxic effects and also through activation of TIL responses.…”

Saikosaponin A Inhibits Triple-Negative Breast Cancer Growth and Metastasis Through Downregulation of CXCR4

“…In addition, we observed that paclitaxel, unlike SSA, increased p-AKT expression in lung tissue and exhibited lower inhibiting efficacy on TNBC lung metastasis than did SSA in the 4T1 mouse model. Wen et al (33) also reported the up-regulation effect of paclitaxel on p-AKT, which suggests a possible mechanism for the relatively poor overall survival of patients with metastatic TNBC treated with paclitaxel (34).…”