Novel Agents for Metastatic Triple-Negative Breast Cancer: Finding the Positive in the Negative

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  • 1 Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
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Metastatic triple-negative breast cancer (TNBC) is associated with a poor prognosis, and the development of better therapeutics represents a major unmet clinical need. Although the mainstay of treatment of metastatic TNBC is chemotherapy, advances in genomics and molecular profiling have helped better define subtypes of TNBC with distinct biologic drivers to guide the therapeutic development of targeted therapies, including AKT inhibitors for PI3K/AKT-altered TNBC, checkpoint inhibitors for PD-L1–positive TNBC, and PARP inhibitors for BRCA1/2 mutant TNBC. This progress may ultimately convert TNBC from a disease traditionally defined by the absence of therapeutically actionable receptors to one that is defined by the presence of discrete molecular targets with therapeutic implications. Furthermore, antibody drug conjugates have emerged as an important therapeutic strategy to target genomically complex tumors that lack actionable oncogenes but have overexpressed actionable surface receptors such as trop-2. In this article, we discuss promising novel agents for advanced TNBC, some of which have been incorporated into current clinical practice, and others that will likely change the therapeutic landscape and redefine the TNBC terminology in the near future.

Submitted January 8, 2020; accepted for publication May 28, 2020. Published online October 14, 2020.

Disclosures: Dr. Vidula has disclosed that she receives honoraria from AbbVie. Dr. Ellisen has disclosed that he has no financial interests, arrangements, or affiliations with the manufacturers of any products discussed in this article or their competitors. Dr. Bardia has disclosed that he is a scientific advisor for Genentech, Immunomedics, Novartis, Pfizer, Merck, Radius Health, Taiho, Diiachi Pharma/Astra Zeneca, Sanofi, Puma Biotechnology, Biothernostics Inc., Phillips, Eli Lilly, and Foundation Medicine; and grant/research support from Genentech, Immunomedics, Novartis, Pfizer, Merck, Sanofi, Radius Health, and Diiachi Pharma/Astra Zeneca.

Correspondence: Neelima Vidula, MD, Massachusetts General Hospital, 55 Fruit Street, Bartlett Hall Extension 1-213, Boston, MA 02114. Email: nvidula@mgh.harvard.edu; and Aditya Bardia, MD, Massachusetts General Hospital, 55 Fruit Street, Bartlett Hall Extension 1-237, Boston, MA 02114. Email: abardia1@mgh.harvard.edu
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