OBJECTIVES: In 2008, the annual medical expenditure on cancer treatment in Japan was approximately 16 trillion yen. In the past decade, a few molecular-targeted drugs (MTDs) were developed for the treatment of HER2+ metastatic breast cancer (HER2-MBC). The number of MTD-treated patients increases every year, which is a concern with regard to the economic impact of cancer therapy. Trastuzumab is the most popular alternative to HER2-MBC therapy in Japan, but it has a high national health insurance price of approximately 220,000 yen per month for women weighing 50 kg. To estimate the clinical and economic burden of breast cancer (BC) and HER2-MBC therapies, we commenced a large clinical database survey, by examining the diagnosis procedure combination (DPC)–based claims, which included flat payment schemes. METHODS: The database, which consists of 15 DPC-targeted institutions that had contracted with Medical Data Vision Ltd., includes approximately 400,000 patients. To extract the pertinent population and estimate the clinical and economic burden of MTDs, a target population consisting of individuals diagnosed with BC on or before March 31, 2010, aged more than 20 years, and treated with MTDs for HER2-MBC was chosen. The observation period was April 1, 2008 to March 31, 2010. RESULTS: During the observation period, 2,419 individuals were diagnosed with BC. Of these, 98 were receiving or had received MTDs. The observed estimated economic cost of BC treatment was 994,000 yen, with an observation duration of approximately 14.0 person-months. The cost of HER2-MBC treatment with MTDs was estimated at 4,455,000 yen with a duration of 17.4 person-months.   CONCLUSION: HER2-MBC therapy seriously impacted the annual medical expenditure in Japan and had a rare survival duration. The database was useful for conducting an economic analysis of cancer treatment in Japan.