OBJECTIVES:  Treatment regimens in extensively pre-treated advanced and metastatic breast cancer (MBC) patients may confer similar efficacy but have different toxicity profiles. This study aimed to identify toxicities associated with chemotherapy regimens in late-line breast cancer and to estimate direct costs of managing those toxicities.METHODS:  A PubMed search identified global Phase II/III studies of single agent and combination treatment regimens for advanced and MBC patients previously treated with ³ 2 chemotherapy regimens.  The proportion of patients experiencing grade 3 and 4 toxicities was abstracted.  Using expert opinion, reported toxicities were placed into representative groupings based on similarities in event types and treatment costs (e.g., extremity pain, pain, arthralgia, headache) and a proxy for each grouping (e.g., pain) was identified for purposes of estimating direct costs of treatment for grade 3 and grade 4 (inpatient) toxicities.  Unit costs were estimated using data from Health Care Utilization Project, Medicare reimbursement rates, and Redbook and updated to 2008 USD using the medical care component of the Consumer Price Index.   RESULTS:  This study included toxicity information from seven treatment regimens studied in the salvage setting.  The most commonly reported grade 3 toxicities were hematological (albumin-bound paclitaxel, capecitabine, gemcitabine, ixabepilone+capecitabine), cardiac (bevacizumab+capecitabine), fatigue (ixabepilone), and gastrointestinal-related (sunitinib).  The most commonly reported grade 4 toxicities were hematological (albumin-bound paclitaxel, capecitabine, ixabepilone, ixabepilone+capecitabine), embolic (bevacizumab+capecitabine) and anemia-related (capecitabine, gemcitabine).  Estimated total direct costs of treating all toxicities by treatment regimen were: sunitinib ($107), gemcitabine ($585), albumin-bound paclitaxel ($1446), bevacizumab+capecitabine ($3493), capecitabine ($3775), ixabepilone ($4403), and ixabepilone+capecitabine ($16279).        CONCLUSIONS: Treatment regimens in extensively pre-treated breast cancer patients may have similar efficacy but vary greatly in the cost of managing treatment-related toxicities:  $107 to $16279 in this study. The costs of these toxicities should be included in future economic evaluations comparing the clinical and cost-effectiveness of alternative treatment regimens for advanced and MBC.