Human epidermal growth factor receptor 2, (HER2) is overexpressed /amplified in multiple carcinomas, for example, gastric cancer(GC), gastroesophageal junction adenocarcinoma(GEJA),and breast cancer.And HER2 is closely related to tumor proliferation &metastases.About 90% Chinese esophagus cancer are squamous cell origin. The reported HER2 overexpression ranged from 5-30%, Beijing cancer hospital reported an 11% positive rate. The variety of HER2 positive rate may because of the absence of standard HER2 testing criteria. The current treatment for metastatic Esophageal squamous Cell Carcinoma (ESCC) is not satisfactory. Fluorouracil and platinum are considered as first line standard of care (SOC) with a 20-30% RR and 7-9 months overall survival (OS). In second line setting, there is no SOC in china. And the efficacy is not satisfactory. Esophageal adenocarcinoma has a higher HER2 positive rate of 14%, but no data reported of using trastuzumab in these patients in China. Biliary tract cancer (BTC), including intrahepatic/extrahepatic cholangiocarcinoma and Gallbladder cancer (GBC) is very aggressive, total 5y survival is less than 5% for unresectable patients. GBC is account for approximately 2/3 of BTC, and it's estimated the incidence in china is 52800 and the mortality is 40700 in 2015. Most patients are diagnosed in advanced stage and lose the opportunity of surgery. However, there is no SOC for unresectable BTC, gemcitabine plus platinum provided a 30% RR and 10 month OS. In second line treatment, no differences were seen between various experimental agents. The reported HER2 positive rate range from 5.1% to 57% in biliary duct cancer and 4.7% to 64% in GBC. Researchers reported her2 amplification is related to tumor stage and lymph nodes metastasis in 221 BTC patients. Another study reported a 16.6% positive rate and worse prognosis with a sample size of 230 GBC patients. Meanwhile, HER2 pathway mutation rate reached 37%. All imply that BTC may be the potential anti HER therapy population. Besides, other digestive system tumor has low HER2 positive rate (Small intestinal cancer 0.9-3%; hepatocellular carcinoma 2.4%; Pancreatic cancer 3%; etc.). However, the patient pool is large and has no SOC in second Line. Whether these HER2 + patients can gain benefit form anti- her treatment is worth investigating. In 2016 American Society of Clinical Oncology (ASCO), a study reported that using trastuzumab and pertuzumab combination, 35% metastatic colorectal cancer (CRC) and 50% BTC patients who heavily pretreated had objective response. However, china doesn't have studies for these patients. .