Triple-Negative Breast Cancers: Systematic Review of the Literature on Molecular and Clinical Features with a Focus on Treatment with Innovative Drugs

Abstract

Over the past decade, the advent of gene expression micro-array technology has led to the identification of different actionable targets including various genomic alterations, androgen receptor, PARP, PI3K, VEGF and other proteins of the angiogenic pathway. Thus, novel targeted drugs have been tested in clinical trials reporting promising results in specific TNBC molecular subgroups. Although cytotoxic chemotherapy remains the mainstay of treatment for TNBC patients, the identification of novel 'drugable' targets and pathways for developing personalized treatments represents a promising investigational approach in the management of the TNBC subtype.

Ilamycin C induces apoptosis and inhibits migration and invasion in triple-negative breast cancer by suppressing IL-6/STAT3 pathway

“…Clinically, TNBC is more aggressive and less sensitive to typical therapies and ultimately has a higher rate of relapse and metastasis and poorer prognosis compared with other subtypes of breast cancer [2,3]. Chemotherapy is the main treatment of TNBC, but chemotherapy resistance has become an inevitable problem [4]. Lack of well-defined molecular targets makes it a challenge to treat and improve the 5-year survival rate of patients with TNBC [5,6].…”

Early Triple Negative Breast Cancer: Conventional Treatment and Emerging Therapeutic Landscapes

“…TNBC is associated with worse prognosis with a high propensity to distant metastases (usually within two or three years from diagnosis) and shorter survival after recurrence. The pattern of relapses is characterized by a preferential metastatic spread to lungs, liver, and brain, while skeletal involvement is less common compared to luminal cancers [2]. Despite the emerging role of targeted therapies, TNBC is still an orphan disease in terms of therapeutic options, and chemotherapy remains the mainstay of treatment.…”

Multitargeted Nanoparticles Deliver Synergistic Drugs across the Blood–Brain Barrier to Brain Metastases of Triple Negative Breast Cancer Cells and Tumor‐Associated Macrophages

“…Triple negative breast cancer (TNBC) is a highly aggressive subtype that accounts for 15–20% of human breast cancers . Owing to the low expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), endocrine and anti‐HER2 therapies are ineffective against TNBC.…”

“…Owing to the low expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), endocrine and anti‐HER2 therapies are ineffective against TNBC. Thus currently, standard adjuvant and neoadjuvant treatments of TNBC are limited to conventional anthracycline‐taxane‐based chemotherapy . Despite the initial response to chemotherapy, TNBC patients have a high risk of relapse and distal metastases, especially to the brain, leading to shortened survival times .…”

“…Despite the initial response to chemotherapy, TNBC patients have a high risk of relapse and distal metastases, especially to the brain, leading to shortened survival times . A number of targeted therapies have been investigated to treat TNBC including poly(ADP‐ribose) polymerase (PARP) inhibitors, immune checkpoint inhibitors, antiandrogen agents, phosphoinositide 3‐kinase inhibitors, mitogen‐activated protein kinase inhibitors, antiangiogenic antibody, and integrin inhibitors …”