title: Triple Negative Breast Cancer: A Tale of Two Decades.
abstract: Triple negative breast cancer (TNBC) is a heterogeneous disease entity constituting about 15% of breast cancer cases worldwide. TNBC is associated with poor prognosis and lack of sustained response to conventional chemotherapeutic agents. Tumoral heterogeneity and the presence of several subtypes of TNBC such as Basal like (BL)-1, BL-2, immune-modulatory, luminal androgen receptor, mesenchymal, and mesenchymal/stem like subtype and claudin low subtype, may explain some of the difficulties faced in managing this challenging disease subgroups. Although no approved targeted therapy is available for TNBCs, molecular-profiling efforts have revealed promising molecular targets such as the vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), polyadenosine ribose polymerase inhibitors (PARPi) and DNA repair pathway, androgen pathway, and NOTCH pathway. TNBC is subject to intense research activities aiming at dissecting potential pathways, identifying potential molecular signatures and biomarkers in order to properly develop new targeted biologic modifiers. Despite this, there is a lack of approved predictive and prognostic biomarkers, and keeping in view the complexity of TNBC biology, research should be targeted towards identifying multi-factorial signatures rather than single markers. This review aims to summarize the current evidence, ongoing research and discuss future strategies for the treatment of patients with TNBC. In addition we have reviewed the recent advances in detecting predictive and prognostic biomarkers and identifying surrogate markers for early identification of potential responders to the new therapies.
authors.affiliation: Oncology Center, King Khalid University Hospital, King Saud University, Saudi Arabia.
authors.forename: Arwa M
authors.initials: AM
authors.lastname: Ali
authors.affiliation: Oncology Center, King Khalid University Hospital, King Saud University, Saudi Arabia.
authors.forename: Jawaher A K
authors.initials: JAK
authors.lastname: Ansari
authors.affiliation: Department of Medical Oncology, South Egypt Cancer Institute, Asyut University, Asyut, Egypt.
authors.forename: Nashwa M Abd
authors.initials: NMA
authors.lastname: El-Aziz
authors.affiliation: Department of Clinical Oncology, Faculty of Medicine, Mansura University, Mansura, Egypt.
authors.forename: Waleed N
authors.initials: WN
authors.lastname: Abozeed
authors.affiliation: Oncology Center, King Khalid University Hospital, King Saud University, Saudi Arabia.
authors.forename: Ahmed M Abdel
authors.initials: AMA
authors.lastname: Warith
authors.affiliation: Oncology Center, King Khalid University Hospital, King Saud University, Saudi Arabia.
authors.forename: Khalid
authors.initials: K
authors.lastname: Alsaleh
authors.affiliation: Oncology Center, King Khalid University Hospital, King Saud University, Saudi Arabia.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Nabholtz
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D004260:DNA Repair / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D011944:Receptors, Androgen / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D064726:Triple Negative Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011944:Receptors, Androgen; D051880:Receptors, Notch; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; Triple negative breast cancer; VEGF; molecular pathways; target therapy