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Biomarkers in triple negative breast cancer:A review

World Journal of Clinical Oncology 2015年第6期6卷 252-263页

作者： Budhi S Yadav Priyanka Chanana swaty jhamb Department of Radiotherapy PGIMER Department of Pharmacology Panjab University Dr HS Judge Institute of Dental Sciences Panjab University

Breast cancer is an intrinsically heterogeneous disease. In the world about 1 million cases of breast cancer are diagnosed annually and more than 170000 are triplenegative. Characteristic feature of triple negative breast cancer(TNBC) is that it lacks expression of oestrogen,progesterone and human epidermal growth factor receptor-2/neu receptors. They comprise 15%-20% of all breast cancers. We did a systematic review of Pub Med and conference databases to identify studies published on biomarkers in TNBC. We included studies with biomarkers including: Epidermal growth factor receptor,vascular endothelial growth factor,c-Myc,C-kit and basal cytokeratins,Poly(ADP-ribose) polymerase-1,p53,tyrosinase kinases,m-TOR,heat and shock proteins and TOP-2A in TNBC. We also looked for studies published on synthetic lethality and inhibition of angiogenesis,growth,and survival pathways. TNBC is a complex disease subtype with many subclasses. Majority TNBC have a basal-like molecular phenotype by gene expression profiling. Their clinical and pathologic features overlap with hereditary BRCA1 related breast cancers. Management of these tumours is a challenge to the clinician because of its aggressive behaviour,poor outcome,and absence of targeted therapies. As the complexity of this disease is being simplified over time new targets are also being discovered for the treatment of this disease. There are many biomarkers in TNBC being used in clinical practice. Biomarkers may be useful as prognostic or predictive indicators as well as suggest possible targets for novel therapies. Many targeted agents are being studied for treatment of TNBC.

关键词： Triple negative breast cancer Epidermal growth factor receptor Vascular endothelial growth factor p53 Cyclin

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Systemic treatment strategies for triple-negative breast cancer

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World Journal of Clinical Oncology 2014年第2期5卷 125-133页

作者： Budhi Singh Yadav Suresh C Sharma Priyanka Chanana swaty jhamb Department of Radiotherapy PGIMERChandigarh 160012 India

Triple-negative breast cancer(TNBC) is defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2(EGFR2). Most TNBC has a basal-like molecular phenotype by gene expression profiling and shares clinical and pathological features with hereditary BRCA1 related breast cancers. This review evaluates the activity of available chemotherapy and targeted agents in TNBC. A systematic review of PubM ed and conference databases was carried out to identify randomised clinical trials reporting outcomes in women with TNBC treated with chemotherapy and targeted agents. Our review identified TNBC studies of chemotherapy and targeted agents with different mechanisms of action, including induction of synthetic lethality and inhibition of angiogenesis, growth and survival pathways. TNBC is sensitive to taxanes and anthracyclins. Platinum agents are effective in TNBC patients with BRCA1 mutation, either alone or in combination with poly adenosine diphosphate polymerase 1 inhibitors. Combinations of ixabepilone and capecitabine have added to progression-free survival(PFS) without survival benefit in metastatic TNBC. Antiangiogenic agents, tyrosine kinase inhibitors and EGFR inhibitorsin combination with chemotherapy produced only modest gains in PFS and had little impact on survival. TNBC subgroups respond differentially to specific targeted agents. In future, the treatment needs to be tailored for a specific patient, depending on the molecular characteristics of their malignancy. TNBC being a chemosensitive entity, combination with targeted agents have not produced substantial improvements in outcomes. Appropriate patient selection with rationale combinations of targeted agents is needed for success.

关键词： Breast cancer Triple negative Basal like BRCA1 Poly(ADP-ribose)polymerase 1 Targeted therapy Chemotherapy

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