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In women with Human Epidermal growth Receptor 2 (HER2)-positive metastatic breast cancer (MBC), Trastuzumab has become the standard of care but previous studies have raised doubts about its economic acceptability. We carried out the first cost-effectiveness study for Trastuzumab in MBC patients, in France, that is based on observed resource use and outcomes in clinical practice.We retrospectively analyzed 47 HER2-positive MBC patients in a before-and-after design study. Nineteen patients did not receive Trastuzumab (“before” Trastuzumab introduction in clinical practice) and 28 patients received Trastuzumab (the “after” population). Direct medical costs were estimated on the basis of the physical quantities reported in the patient medical records, for the period from first metastatic progression until death or date of patient last news. Monetary values (2002 French francs) were attributed to these quantities on the basis of unit costs and incremental cost-effectiveness ratios were calculated.In the Trastuzumab group, median overall survival was significantly higher (37 months vs. 19 months in the non-Ttrastuzumab group, P = 0.001) but total treatment costs were 3 times higher (€39,608 vs. €12,795). The cost per additional life-year saved by Trastuzumab treatment was estimated to be €27,492 (95% confidence interval: €20,964-€34,020/year of life [bootstrapped estimation]).Our data suggest that despite its high unit price, Trastuzumab should be considered cost-effective in MBC patients to the extent that its incremental cost per life-year saved remains lower than gross domestic product per capita in countries like France.