The standard treatment for HER2-positive breast cancer is HER2 targeted therapy. However, some patients acquired resistance after HER2 targeted therapy, leading to treatment failure. For those patients, chemotherapy may be the ultimate choice and therefore additional treatment options are necessary. Previously, an immune checkpoint inhibitor, pembrolizumab, had shown clinical activity in heavily pretreated TNBC patients. Therefore, researchers conducted a phase Ib/II PANACEA trial enrolling 58 patients to assess the efficacy of pembrolizumab combined with trastuzumab in trastuzumab-resistant, PD-L1-positive, HER2-positve breast cancers. The results showed that objective response rate (ORR) was 15.2% and the disease control rate (DCR) was 24%. Among the responders, there were two complete responses and five partial responses. Furthermore, high levels of stromal tumor-infiltrating lymphocyte (sTIL) is correlated with better response rate, indicating a potential biomarker for use. The response rate was 39% in the sTIL>5% group, comparing to 5% in the sTIL< 5% group. These findings indicate that pembrolizumab combined with trastuzumab may be effective in PD-L1 positive, HER2 positive breast cancer patients who fail to respond to trastuzumab and call for further larger studies to confirm the clinical utility of this combination therapy.