OBJECTIVES  To compare health care resource utilization (HRU) and costs by line of therapy (LOT) among patients with metastatic breast cancer (MBC). METHODS MarketScan® databases, January 1, 2005 to December 31, 2009, were used to identify women aged ≥18 with breast cancer (ICD-9-CM of 174.xx). The index date was the first prescription fill or administration of anti-neoplastic agents. Either a 90-day gap in treatment or initiation of a new regimen ended each LOT. Per patient per month (PPPM) expenditures for utilizers of  inpatient (IP), outpatient (OP), emergency department visits (ED), MBC-drugs (oral and infused), hormonal, radiology, and supportive therapies  across four LOTs (1L-first line, 2L-second, 3L-third, 4L-fourth)  were statistically compared. HRU rates (Visits per patient with ≥1 Visit) were also compared. RESULTS A total of 8494 MBC patients (1L:7,765; 2L:4,077; 3L:2,033, 4L:1,059) were included. Bone metastases were  most common (43.9%) at index followed by liver (17.7%) and lung (12.8%).   PPPM expenditures for IP (1L:$1,183, 2L:$1,318, 3L: $1,401,  4L:$1,670; p=0.660), OP (1L:$1,751, 2L:$1,624; 3L: $1,626; 4L:$1,626, p=0.413), and ED (1L:$64, 2L:$67, 3L: $73,  4L:$57 p=0.997) were not stastically siginificantly different across the four LOTs. PPPM expenditures for MBC oral-drugs (1L:$460, 2L:$530, 3L:$589, 4L:$743,p=0.37), hormonal (1L:$87 , 2L:$65, 3L: $70, and 4L:$55,p=0.388), and radiology therapies (1L:$290,2L:$280,3L: $280,and 4L:$271, p=0.999) were also not statistically different across LOTs. MBC infused-drugs (1L:$4096,2L:$4,607,3L:$4,841, 4L:$4,521,p=0.001) did differ.  Within  supportives, PPPM across LOTs were stastically different for anti-emetics (1L:$283,2L:$321;3L: $320;4L:$311,p=0.007) and pain medications (1L:$42,2L:$50;3L:$62;4L:$71,p=0.002) but not  for IV-bisphosphonates (1L:$406,2L:$412;3L:$419;4L:$410,p=0.964). The mean HRU rates for IP (range1.4-1.4), ED (1.7-1.8), OP hospial (8.4-9.4) office-visit (11.2-12.6), and Other outpatient visits (18.9-20.5,) were similar across LOTs. CONCLUSIONS  No significant variation in the PPPM costs of (IP, OP, ED, MBC oral drugs, hormonal, radiology, or IV bisphosphonates) was oberved across four LOTs.  LOT costs differed  for infused drugs, anti-emetics, and pain medication within this MBC population. Further research is required to explore these variations.