Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Mar 24, 2021; 12(3): 164-182
Published online Mar 24, 2021. doi: 10.5306/wjco.v12.i3.164
Overview of recent advances in metastatic triple negative breast cancer
David O'Reilly, Maha Al Sendi, Catherine M Kelly
David O'Reilly, Maha Al Sendi, Catherine M Kelly, Department of Medical Oncology, Mater Misericordiae University Hospital, Dublin 1, Ireland
Author contributions: O'Reilly D wrote the main body of the manuscript; Sendi MA wrote the section on targeted therapies and reviewed the manuscript; Kelly CM provided guidance in the structure of the manuscript and reviewed the manuscript as the senior author.
Conflict-of-interest statement: The authors have no conflict of interests to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: David O'Reilly, MBChB, MRCP, Academic Fellow, Department of Medical Oncology, Mater Misericordiae University Hospital, Eccles St, Dublin 1, Ireland.
Received: November 26, 2020
Peer-review started: November 26, 2020
First decision: December 11, 2020
Revised: January 2, 2021
Accepted: March 1, 2021
Article in press: March 1, 2021
Published online: March 24, 2021

Metastatic triple negative breast cancer (TNBC) has an aggressive phenotype with a predilection for visceral organs and brain. Best responses to chemotherapy are predominately in the first line. Recent studies have demonstrated improved progression free survival with the combination of atezolizumab/pembrolizumab and chemotherapy in programmed death-ligand 1 positive metastatic TNBC. However, a recent trial in a similar population showed no benefit for atezoli-zumab and paclitaxel which led to a Food and Drug Administration alert. Two phase III trials (OLYMPIAD and BROCADE3) demonstrated a benefit in progression free survival (PFS) but not overall survival in patients with BRCA-associated metastatic TNBC treated with Olaparib or Talazoparib respectively. For those treated with Talazoparib, the time to deterioration in health related-quality of life was also longer compared to chemotherapy. The BROCADE3 trial demonstrated that the combination of a platinum and veliparib increased PFS in first-line metastatic TNBC but at the cost of increased toxicity. There are no head-to-head comparisons of a poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and platinums. There are unanswered questions regarding the role of PARPi maintenance after platinum therapy as is standard of care in BRCA-associated ovarian cancer. Other areas of therapeutic interest include targeting aberrations in the phosphoinositide 3-kinase pathway, protein kinase B, mammalian target of rapamycin or utilising antibody drug conjugates. This review focusses on recent and emerging therapeutic options in metastatic TNBC. We searched PubMed, and recent international meetings from American Society of Clinical Oncology, San Antonio Breast Cancer Conference and the European Society of Medical Oncology.

Keywords: Triple negative breast cancer, Immunotherapy, Poly (adenosine diphosphate-ribose) polymerase inhibitors, Breast cancer

Core Tip: Despite recent advances, chemotherapy remains integral to the management of advanced triple negative breast cancer. Immunotherapy and poly (adenosine diphosphate-ribose) polymerase inhibitors have shown much promise but have yet to demonstrate a proven overall survival benefit in this disease. Antibody drug conjugates and other targeted therapies may ultimately prove to be the next frontier in treating this illness.