Personalised Therapies for Metastatic Triple-Negative Breast Cancer: When Target Is Not Everything

Abstract

Triple-negative breast cancer—defined by the absence of oestrogen/progesterone receptors and human epidermal growth factor receptor 2 expression—is a complex and heterogeneous type of tumour characterised by poor prognosis, aggressive behaviour and lack of effective therapeutic strategies. The identification of new biomarkers and molecular signatures is leading to development of new therapeutic strategies including immunotherapy, targeted therapy and antibody-drug conjugates (ADCs). Against a background where chemotherapy has always been considered the standard of care, evolution towards a precision medicine approach could improve TNBC clinical practice in a complex scenario, with many therapeutic options and new drugs. The aim of this review was to focus on emerging therapeutic targets and their related specific therapy, discussing available and emerging drugs, underlining differences in approval by American and European regulatory authorities and showing the future perspective in the large number of ongoing clinical trials.

Differential Expression of NOTCH-1 and Its Molecular Targets in Response to Metronomic Followed by Conventional Therapy in a Patient with Advanced Triple-Negative Breast Cancer

“…In fact, given the heterogeneity of TNBC [33] and these various characteristics-including pharmacological properties, tumor cell characteristics, and environmental factors-influence the clinical responses, it is of paramount importance to unveil the biological characteristics of the patients who better respond to therapy and understand which therapeutic strategies may be more suitable for individual patients. In a scenario in which chemotherapy is supported by only a few other effective tools against this subtype of breast cancer, mCHT plays a role that is destined to be increasingly central in the treatment of patients affected by mTNBC, especially considering that tumors can develop resistance due to intrinsic and acquired factors or a combination of both [34].…”

A phase II study of a doublet metronomic chemotherapy regimen consisting of oral vinorelbine and capecitabine in Chinese women with HER2‐negative metastatic breast cancer

“…Endocrine therapy is the standard initial treatment option for advanced HR‐positive, HER‐2‐negative BC cases, except those with visceral crisis or primary endocrine resistance 17 . In patients with TNBC, chemotherapy is the main treatment option 18,19 . Nevertheless, resistance invariably emerged among patients with HR‐positive, HER‐2‐negative BC or TNBC, and patients exhibited reduced tolerance to the treatment drugs with increasing number of treatment lines 20 .…”

“… 17 In patients with TNBC, chemotherapy is the main treatment option. 18 , 19 Nevertheless, resistance invariably emerged among patients with HR‐positive, HER‐2‐negative BC or TNBC, and patients exhibited reduced tolerance to the treatment drugs with increasing number of treatment lines. 20 Therefore, determining an effective and low‐toxicity treatment regimen is crucial to addressing this issue.…”