[Combination Therapy of Molecular-Targeted Drugs for Breast Cancer -- Their Potential in the Future].

In breast cancer treatment, molecular-targeted drugs such as trastuzumab and lapatinib have been used for many y ears, and the benefits have been seen in many patients. The molecular-targeted drugs have mainly been used in combination with cytotoxic agents; however, combination therapies with 2 molecular-targeted drugs are currently being investigated. The combination therapy of 2 HER2 receptor antibodies, pertuzumab and trastuzumab, has tremendous benefit for HER2 positive metastatic breast cancer patients. However, the combination of trastuzumab with tyrosine-kinase inhibitor lapatinib showed small benefits and its usage is limited. The combination of T-DM1 plus pertuzumab was not anymore effective than T-DM1 alone. The potentials of combined hormone therapies have been examined for ages. The combination of fulvestrant and aromatase inhibitor(AI)was shown to be beneficial in one phase III study; however, a conflicting result was reported by another large trial. To overcome hormone therapy resistance, the combinations of hormone therapy drugs with mTOR inhibitors(everolimus), pan-PI3K inhibitor(buparlisib), and CDK4/6 inhibitors(palbociclib, ribociclib, abemaciclib)are being investigated in various settings.