title: New Therapeutic Strategies for Triple-Negative Breast Cancer.
abstract: Relatively few clinically important therapeutic advances have occurred in the treatment of triple-negative breast cancer (TNBC) since the introduction of taxanes as adjuvant therapy over 20 years ago. However, this is rapidly changing due to a variety of conceptually important clinical trials and emerging new options such as immune checkpoint inhibitors and antibody-drug conjugates. Evidence also increasingly supports that platinum drugs and inhibitors of poly (ADP-ribose) polymerase, or PARP, are particularly effective in the treatment of germline BRCA-mutant cancers, including TNBC. An important development in early-stage TNBC was the recognition that extensive residual cancer after neoadjuvant chemotherapy identifies patients who remain at high risk for recurrence. This has led to the design of two ongoing adjuvant trials (one testing pembrolizumab, the other investigating platinum drugs and capecitabine) that offer a "second chance" to improve the survival of patients with residual cancer after neoadjuvant chemotherapy. Genomic analysis of TNBC has revealed large-scale transcriptional, mutational, and copy number heterogeneity, without any frequently recurrent mutations, other than TP53. Consistent with this molecular heterogeneity, most targeted agents, so far, have demonstrated low overall activity in unselected TNBC, but important "basket" trials are ongoing.
authors.forename: Borbála
authors.initials: B
authors.lastname: Székely
authors.forename: Andrea L M
authors.initials: AL
authors.lastname: Silber
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
mesh_terms: D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D020360:Neoadjuvant Therapy; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy*
chemical_list: D056572:Histone Deacetylase Inhibitors; D018796:Immunoconjugates; D000067856:Poly(ADP-ribose) Polymerase Inhibitors