Targeted Therapies in Triple-Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous disease comprised of several biologically distinct subtypes. However, treatment is currently mainly relying on chemotherapy as there are no targeted therapies specifically approved for TNBC. Despite initial responses to chemotherapy, resistance frequently and rapidly develops and metastatic TNBC has a poor prognosis. New targeted approaches are, therefore, urgently needed. Currently, bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF)-A antibody, is the only targeted agent with an approval for the therapy of metastatic breast cancer, but does not provide a specific benefit in the TNBC subtype. This review discusses the current clinical developments in targeted approaches for TNBC, including anti-angiogenic therapies, epidermal growth factor receptor (EGFR)-targeted therapies, poly(ADP-ribose) polymerase (PARP) inhibitors and platinum salts, as well as novel strategies using immune-checkpoint inhibitors, which have recently demonstrated first promising results. Strategies focusing on specific subtypes of TNBC like anti-androgenic therapies for the luminal androgen receptor subtype (LAR) and others are also discussed.

Targeted therapies in breast cancer: New challenges to fight against resistance

“…The identification of new target molecules in breast cancer and the use of combination therapies may have improved the understanding of compensatory pathways which lead to the emergence of resistance mechanisms, nevertheless, breast cancer subtypes like TNBCs seem to exploit alternative proliferative pathways which are not yet fully understood and need urgent attention and elucidation[11] (Figure 1). …”

SPARC overexpression in primary tumors correlates with disease recurrence and overall survival in patients with triple negative breast cancer

“…Accounting for 10-17% of all breast carcinomas, triple-negative breast cancer (TNBC), which lacks the expression of estrogen receptor (ER), progesterone receptor (PR) and HER2, is the most aggressive subtype and is known for its poor prognosis and high recurrence probability [2]. TNBC tumors are often larger at presentation and possess more advanced histologic grade compared to ER/PR positive breast cancers [3]. Biomarkers for TNBC prognosis are currently ill defined, making it the true challenge to the modern oncology.…”

Integrated in vivo genetic and pharmacologic screening identifies co-inhibition of EGRF and ROCK as a potential treatment regimen for triple-negative breast cancer

“…Numerous clinical studies have been conducted in recent years to assess the effectiveness of targeted agents such as PARP, EGFR and VEGF inhibitors in different settings. These efforts, however, either failed to significantly improve patient survival or were inconclusive [12, 13]. It therefore is crucial and urgent to identify novel therapeutic targets to treat TNBC.…”