Triple-negative Breast Cancer: New Strategies for Targeted Therapy
Despite the success of targeted therapy in other cancers, targeted therapy has failed to improve outcomes in triple-negative breast cancer.
Despite the success of targeted therapy in other cancers, targeted therapy has failed to improve outcomes in triple-negative breast cancer (TNBC).
A potential strategy to mitigate this lack of efficacy is to further study cross-talk between the epidermal growth factor receptor (EGFR) and other oncogenic signaling pathways, according to a review published in Cancer Treatment Reviews.1
EGFR is expressed in up to 90% of TNBCs compared to less than 50% of HER2-positive and luminal B breast cancers. As a result, EGFR-targeted therapies have been investigated in TNBC, though efficacy is not established.
“So far, clinical studies failed to yield encouraging results with the use of EGFR-directed monoclonal antibodies in unselected TNBC,” wrote the authors. Treatment with the anti-EGFR antibodies cetuximab or panitumumab combined with chemotherapy has produced mixed results, with most phase 2 trials showing no improvement in progression-free or overall survival.
Novel approaches are being studied to improve outcomes using targeted therapy in TNBC. One approach is to combine antibodies that target different epitopes to accelerate receptor degradation. In a TNBC xenograft mouse model, cetuximab combined with other anti-EGFR antibodies increased its efficacy.
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Another approach is the use of antibody-drug conjugates (ADCs), which are a class of agents in which an antibody is used to bring a cytotoxic agent to a specific site. An example of an ADC used in HER2-positive breast cancer is trastuzumab emtansine, which significantly prolongs overall survival compared with capecitabine and lapatinib for patients with metastatic disease.