New Therapeutic Strategies for Triple-Negative Breast Cancer. 2017

Borbála Székely, and Andrea L M Silber, and Lajos Pusztai

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.

UI MeSH Term Description Entries
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000067856 Poly(ADP-ribose) Polymerase Inhibitors Chemicals and drugs that inhibit the action of POLY(ADP-RIBOSE)POLYMERASES. Inhibitors of Poly(ADP-ribose) Polymerase,PARP Inhibitor,Poly(ADP-Ribose) Polymerase Inhibitor,Poly(ADP-ribosylation) Inhibitor,Inhibitors of Poly(ADP-ribose) Polymerases,PARP Inhibitors,Poly(ADP-ribosylation) Inhibitors,Inhibitor, PARP,Inhibitors, PARP
D056572 Histone Deacetylase Inhibitors Compounds that inhibit HISTONE DEACETYLASES. This class of drugs may influence gene expression by increasing the level of acetylated HISTONES in specific CHROMATIN domains. HDAC Inhibitor,HDAC Inhibitors,Histone Deacetylase Inhibitor,Deacetylase Inhibitor, Histone,Deacetylase Inhibitors, Histone,Inhibitor, HDAC,Inhibitor, Histone Deacetylase,Inhibitors, HDAC,Inhibitors, Histone Deacetylase
D018796 Immunoconjugates Combinations of diagnostic or therapeutic substances linked with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; or ANTIGENS. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of DRUGS and RADIOISOTOPES in the CHEMOTHERAPY and RADIOIMMUNOTHERAPY of certain cancers. Antibody Drug Conjugate,Antibody-Drug Conjugate,Radioimmunoconjugates,Antibody-Drug Conjugates,Immunoconjugate,Radioimmunoconjugate,Antibody Drug Conjugates,Conjugate, Antibody Drug,Conjugate, Antibody-Drug,Conjugates, Antibody-Drug,Drug Conjugate, Antibody
D020360 Neoadjuvant Therapy Preliminary cancer therapy (chemotherapy, radiation therapy, hormone/endocrine therapy, IMMUNOTHERAPY, HYPERTHERMIA, INDUCED etc.) that is given before the main therapy. Neoadjuvant Chemoradiation,Neoadjuvant Chemoradiation Therapy,Neoadjuvant Chemoradiation Treatment,Neoadjuvant Chemoradiotherapy,Neoadjuvant Chemotherapy,Neoadjuvant Chemotherapy Treatment,Neoadjuvant Radiation,Neoadjuvant Radiation Therapy,Neoadjuvant Radiation Treatment,Neoadjuvant Radiotherapy,Neoadjuvant Systemic Therapy,Neoadjuvant Systemic Treatment,Neoadjuvant Treatment,Chemoradiation Therapy, Neoadjuvant,Chemoradiation Treatment, Neoadjuvant,Chemoradiation, Neoadjuvant,Chemoradiotherapy, Neoadjuvant,Chemotherapy Treatment, Neoadjuvant,Chemotherapy, Neoadjuvant,Neoadjuvant Chemoradiation Therapies,Neoadjuvant Chemoradiation Treatments,Neoadjuvant Chemoradiations,Neoadjuvant Chemoradiotherapies,Neoadjuvant Chemotherapies,Neoadjuvant Chemotherapy Treatments,Neoadjuvant Radiation Therapies,Neoadjuvant Radiation Treatments,Neoadjuvant Radiations,Neoadjuvant Radiotherapies,Neoadjuvant Systemic Therapies,Neoadjuvant Systemic Treatments,Neoadjuvant Therapies,Neoadjuvant Treatments,Radiation Therapy, Neoadjuvant,Radiation Treatment, Neoadjuvant,Radiation, Neoadjuvant,Radiotherapy, Neoadjuvant,Systemic Therapy, Neoadjuvant,Systemic Treatment, Neoadjuvant,Therapy, Neoadjuvant,Therapy, Neoadjuvant Chemoradiation,Therapy, Neoadjuvant Radiation,Therapy, Neoadjuvant Systemic,Treatment, Neoadjuvant,Treatment, Neoadjuvant Chemoradiation,Treatment, Neoadjuvant Chemotherapy,Treatment, Neoadjuvant Radiation,Treatment, Neoadjuvant Systemic
D064726 Triple Negative Breast Neoplasms Breast neoplasms that do not express ESTROGEN RECEPTORS; PROGESTERONE RECEPTORS; and do not overexpress the NEU RECEPTOR/HER-2 PROTO-ONCOGENE PROTEIN. ER-Negative PR-Negative HER2-Negative Breast Cancer,ER-Negative PR-Negative HER2-Negative Breast Neoplasms,Triple Negative Breast Cancer,Triple-Negative Breast Cancer,Triple-Negative Breast Neoplasm,Breast Cancer, Triple-Negative,Breast Cancers, Triple-Negative,Breast Neoplasm, Triple-Negative,Breast Neoplasms, Triple-Negative,ER Negative PR Negative HER2 Negative Breast Cancer,ER Negative PR Negative HER2 Negative Breast Neoplasms,Triple Negative Breast Neoplasm,Triple-Negative Breast Cancers,Triple-Negative Breast Neoplasms

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