Biomarkers in Triple-Negative Breast Cancer: State-of-the-Art and Future Perspectives

Abstract

<jats:p>Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors characterized by aggressive behavior, high risk of distant recurrence, and poor survival. Chemotherapy is still the main therapeutic approach for this subgroup of patients, therefore, progress in the treatment of TNBC remains an important challenge. Data derived from molecular technologies have identified TNBCs with different gene expression and mutation profiles that may help developing targeted therapies. So far, however, only a few of these have shown to improve the prognosis and outcomes of TNBC patients. Robust predictive biomarkers to accelerate clinical progress are needed. Herein, we review prognostic and predictive biomarkers in TNBC, discuss the current evidence supporting their use, and look at the future of this research field.</jats:p>

Targeting Autophagy in Breast Cancer

“…As mentioned above, TNBC tumors are characterized by a more aggressive behavior and early relapse [103]. Higher levels of basal autophagy were found in the metastatic cell lines when compared to the non-metastatic, suggesting that autophagy could promote invasiveness and possibly increase tolerance to the cellular stress occurring during the metastatic process [143].…”

“…Finally, TNBC are more likely to exhibit an aggressive phenotype that become metastatic and resistant to various chemotherapeutics [103]. Atezolizumab, an immunocheckpoint inhibitor targeting the protein programmed cell death-ligand 1 (PDL1), was recently approved in combination with nab-paclitaxel, in the treatment of patients with unresectable locally advanced or metastatic PDL1-positive TNBC [104], however, chemotherapy is still the standard of care in many early or advanced TNBC tumors.…”

“…The increase in autophagy, induced by PI3K/AKT/mTOR inhibitors, is not surprising due to their inhibition of mTOR signaling, control of autophagy initiation and ULK1/2 phosphorylation. Recently, Alpelisib, an oral α-specific PI3K inhibitor, was approved, in metastatic setting [118], while other PI3K/AKT/mTOR inhibitors, such as Taselisib (PI3K inhibitor), Ipatasertib, and Capivasertib (AKT inhibitors) are in clinical investigation [103]. Recently, Zhai et al reported that Ipatasertib was able to induce ACD in hepatocellular carcinoma models [119], while, Zorea et al showed that an ovarian cancer cell line treated with Taselisib activates autophagy to avoid cell death [120].…”

“…In the last years, preclinical and clinical research focused on targeting different pathways involved in tumor growth, such as PI3K/Akt/mTOR, cyclinD/CDK/pRb pathways and tumor microenvironment [ 103 , 105 , 106 ]. In this regard, inhibition of autophagy has proven to improve the drug response and reduce the mechanism of drug resistance [ 11 , 32 , 41 ].…”

Novel biomarkers and prediction model for the pathological complete response to neoadjuvant treatment of triple-negative breast cancer

“…Although systemic treatment is the essential composition of the therapeutic introduction for triplenegative breast cancer, the pCR rate is just 35-40% of the whole group of patients based on the application of standard-of-care protocols. Besides, several efforts have been put in the eld of pCR prediction including both clinical and experimental management, however, except for a few predictors such as BRCA1 de ciency for TNBC treated with platinum-containing NCT, no e cient biomarkers have been yet generally recommended [4][5][6][7][8][9]. This dilemma could be the result of molecular heterogeneities of TNBC.…”