title: Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500.
abstract: OBJECTIVE
  Increased circulating tumor cells (CTCs; five or more CTCs per 7.5 mL of whole blood) are associated with poor prognosis in metastatic breast cancer (MBC). A randomized trial of patients with persistent increase in CTCs tested whether changing chemotherapy after one cycle of first-line chemotherapy would improve the primary outcome of overall survival (OS).
  
  
  METHODS
  Patients with MBC who did not have increased CTCs at baseline remained on initial therapy until progression (arm A). Patients with initially increased CTCs that decreased after 21 days of therapy remained on initial therapy (arm B). Patients with persistently increased CTCs after 21 days of therapy were randomly assigned to continue initial therapy (arm C1) or change to an alternative chemotherapy (arm C2).
  
  
  RESULTS
  Of 595 eligible and evaluable patients, 276 (46%) did not have increased CTCs (arm A). Of those with initially increased CTCs, 31 (10%) were not retested, 165 were assigned to arm B, and 123 were randomly assigned to arm C1 or C2. No difference in median OS was observed between arm C1 and C2 (10.7 and 12.5 months, respectively; P = .98). CTCs were strongly prognostic. Median OS for arms A, B, and C (C1 and C2 combined) were 35 months, 23 months, and 13 months, respectively (P < .001).
  
  
  CONCLUSIONS
  This study confirms the prognostic significance of CTCs in patients with MBC receiving first-line chemotherapy. For patients with persistently increased CTCs after 21 days of first-line chemotherapy, early switching to an alternate cytotoxic therapy was not effective in prolonging OS. For this population, there is a need for more effective treatment than standard chemotherapy.
authors.affiliation: Jeffrey B. Smerage, Anne F. Schott, and Daniel F. Hayes, University of Michigan Comprehensive Cancer Center, Ann Arbor; Gordan Srkalovic, Sparrow Regional Cancer Center, Lansing; Sheela Tejwani, Henry Ford Hospital, Detroit, MI; William E. Barlow and Danika L. Lew, SWOG Statistical Center; Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA; Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston, TX; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Brian Leyland-Jones, Avera Cancer Institute, Sioux Falls, SD; Mark A. O'Rourke, Greenville Health System Cancer Institute/Greenville Community Clinical Oncology Program, Greenville, SC; Gerald V. Doyle, Immunicon, Huntingdon Valley, PA; and Robert B. Livingston, University of Arizona Cancer Center, Tucson, AZ.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Smerage
authors.affiliation: Jeffrey B. Smerage, Anne F. Schott, and Daniel F. Hayes, University of Michigan Comprehensive Cancer Center, Ann Arbor; Gordan Srkalovic, Sparrow Regional Cancer Center, Lansing; Sheela Tejwani, Henry Ford Hospital, Detroit, MI; William E. Barlow and Danika L. Lew, SWOG Statistical Center; Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA; Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston, TX; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Brian Leyland-Jones, Avera Cancer Institute, Sioux Falls, SD; Mark A. O'Rourke, Greenville Health System Cancer Institute/Greenville Community Clinical Oncology Program, Greenville, SC; Gerald V. Doyle, Immunicon, Huntingdon Valley, PA; and Robert B. Livingston, University of Arizona Cancer Center, Tucson, AZ.
authors.forename: William E
authors.initials: WE
authors.lastname: Barlow
authors.affiliation: Jeffrey B. Smerage, Anne F. Schott, and Daniel F. Hayes, University of Michigan Comprehensive Cancer Center, Ann Arbor; Gordan Srkalovic, Sparrow Regional Cancer Center, Lansing; Sheela Tejwani, Henry Ford Hospital, Detroit, MI; William E. Barlow and Danika L. Lew, SWOG Statistical Center; Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA; Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston, TX; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Brian Leyland-Jones, Avera Cancer Institute, Sioux Falls, SD; Mark A. O'Rourke, Greenville Health System Cancer Institute/Greenville Community Clinical Oncology Program, Greenville, SC; Gerald V. Doyle, Immunicon, Huntingdon Valley, PA; and Robert B. Livingston, University of Arizona Cancer Center, Tucson, AZ.
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.affiliation: Jeffrey B. Smerage, Anne F. Schott, and Daniel F. Hayes, University of Michigan Comprehensive Cancer Center, Ann Arbor; Gordan Srkalovic, Sparrow Regional Cancer Center, Lansing; Sheela Tejwani, Henry Ford Hospital, Detroit, MI; William E. Barlow and Danika L. Lew, SWOG Statistical Center; Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA; Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston, TX; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Brian Leyland-Jones, Avera Cancer Institute, Sioux Falls, SD; Mark A. O'Rourke, Greenville Health System Cancer Institute/Greenville Community Clinical Oncology Program, Greenville, SC; Gerald V. Doyle, Immunicon, Huntingdon Valley, PA; and Robert B. Livingston, University of Arizona Cancer Center, Tucson, AZ.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
authors.affiliation: Jeffrey B. Smerage, Anne F. Schott, and Daniel F. Hayes, University of Michigan Comprehensive Cancer Center, Ann Arbor; Gordan Srkalovic, Sparrow Regional Cancer Center, Lansing; Sheela Tejwani, Henry Ford Hospital, Detroit, MI; William E. Barlow and Danika L. Lew, SWOG Statistical Center; Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA; Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston, TX; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Brian Leyland-Jones, Avera Cancer Institute, Sioux Falls, SD; Mark A. O'Rourke, Greenville Health System Cancer Institute/Greenville Community Clinical Oncology Program, Greenville, SC; Gerald V. Doyle, Immunicon, Huntingdon Valley, PA; and Robert B. Livingston, University of Arizona Cancer Center, Tucson, AZ.
authors.forename: Brian
authors.initials: B
authors.lastname: Leyland-Jones
authors.affiliation: Jeffrey B. Smerage, Anne F. Schott, and Daniel F. Hayes, University of Michigan Comprehensive Cancer Center, Ann Arbor; Gordan Srkalovic, Sparrow Regional Cancer Center, Lansing; Sheela Tejwani, Henry Ford Hospital, Detroit, MI; William E. Barlow and Danika L. Lew, SWOG Statistical Center; Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA; Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston, TX; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Brian Leyland-Jones, Avera Cancer Institute, Sioux Falls, SD; Mark A. O'Rourke, Greenville Health System Cancer Institute/Greenville Community Clinical Oncology Program, Greenville, SC; Gerald V. Doyle, Immunicon, Huntingdon Valley, PA; and Robert B. Livingston, University of Arizona Cancer Center, Tucson, AZ.
authors.forename: Gordan
authors.initials: G
authors.lastname: Srkalovic
authors.affiliation: Jeffrey B. Smerage, Anne F. Schott, and Daniel F. Hayes, University of Michigan Comprehensive Cancer Center, Ann Arbor; Gordan Srkalovic, Sparrow Regional Cancer Center, Lansing; Sheela Tejwani, Henry Ford Hospital, Detroit, MI; William E. Barlow and Danika L. Lew, SWOG Statistical Center; Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA; Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston, TX; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Brian Leyland-Jones, Avera Cancer Institute, Sioux Falls, SD; Mark A. O'Rourke, Greenville Health System Cancer Institute/Greenville Community Clinical Oncology Program, Greenville, SC; Gerald V. Doyle, Immunicon, Huntingdon Valley, PA; and Robert B. Livingston, University of Arizona Cancer Center, Tucson, AZ.
authors.forename: Sheela
authors.initials: S
authors.lastname: Tejwani
authors.affiliation: Jeffrey B. Smerage, Anne F. Schott, and Daniel F. Hayes, University of Michigan Comprehensive Cancer Center, Ann Arbor; Gordan Srkalovic, Sparrow Regional Cancer Center, Lansing; Sheela Tejwani, Henry Ford Hospital, Detroit, MI; William E. Barlow and Danika L. Lew, SWOG Statistical Center; Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA; Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston, TX; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Brian Leyland-Jones, Avera Cancer Institute, Sioux Falls, SD; Mark A. O'Rourke, Greenville Health System Cancer Institute/Greenville Community Clinical Oncology Program, Greenville, SC; Gerald V. Doyle, Immunicon, Huntingdon Valley, PA; and Robert B. Livingston, University of Arizona Cancer Center, Tucson, AZ.
authors.forename: Anne F
authors.initials: AF
authors.lastname: Schott
authors.affiliation: Jeffrey B. Smerage, Anne F. Schott, and Daniel F. Hayes, University of Michigan Comprehensive Cancer Center, Ann Arbor; Gordan Srkalovic, Sparrow Regional Cancer Center, Lansing; Sheela Tejwani, Henry Ford Hospital, Detroit, MI; William E. Barlow and Danika L. Lew, SWOG Statistical Center; Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA; Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston, TX; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Brian Leyland-Jones, Avera Cancer Institute, Sioux Falls, SD; Mark A. O'Rourke, Greenville Health System Cancer Institute/Greenville Community Clinical Oncology Program, Greenville, SC; Gerald V. Doyle, Immunicon, Huntingdon Valley, PA; and Robert B. Livingston, University of Arizona Cancer Center, Tucson, AZ.
authors.forename: Mark A
authors.initials: MA
authors.lastname: O'Rourke
authors.affiliation: Jeffrey B. Smerage, Anne F. Schott, and Daniel F. Hayes, University of Michigan Comprehensive Cancer Center, Ann Arbor; Gordan Srkalovic, Sparrow Regional Cancer Center, Lansing; Sheela Tejwani, Henry Ford Hospital, Detroit, MI; William E. Barlow and Danika L. Lew, SWOG Statistical Center; Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA; Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston, TX; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Brian Leyland-Jones, Avera Cancer Institute, Sioux Falls, SD; Mark A. O'Rourke, Greenville Health System Cancer Institute/Greenville Community Clinical Oncology Program, Greenville, SC; Gerald V. Doyle, Immunicon, Huntingdon Valley, PA; and Robert B. Livingston, University of Arizona Cancer Center, Tucson, AZ.
authors.forename: Danika L
authors.initials: DL
authors.lastname: Lew
authors.affiliation: Jeffrey B. Smerage, Anne F. Schott, and Daniel F. Hayes, University of Michigan Comprehensive Cancer Center, Ann Arbor; Gordan Srkalovic, Sparrow Regional Cancer Center, Lansing; Sheela Tejwani, Henry Ford Hospital, Detroit, MI; William E. Barlow and Danika L. Lew, SWOG Statistical Center; Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA; Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston, TX; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Brian Leyland-Jones, Avera Cancer Institute, Sioux Falls, SD; Mark A. O'Rourke, Greenville Health System Cancer Institute/Greenville Community Clinical Oncology Program, Greenville, SC; Gerald V. Doyle, Immunicon, Huntingdon Valley, PA; and Robert B. Livingston, University of Arizona Cancer Center, Tucson, AZ.
authors.forename: Gerald V
authors.initials: GV
authors.lastname: Doyle
authors.affiliation: Jeffrey B. Smerage, Anne F. Schott, and Daniel F. Hayes, University of Michigan Comprehensive Cancer Center, Ann Arbor; Gordan Srkalovic, Sparrow Regional Cancer Center, Lansing; Sheela Tejwani, Henry Ford Hospital, Detroit, MI; William E. Barlow and Danika L. Lew, SWOG Statistical Center; Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA; Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston, TX; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Brian Leyland-Jones, Avera Cancer Institute, Sioux Falls, SD; Mark A. O'Rourke, Greenville Health System Cancer Institute/Greenville Community Clinical Oncology Program, Greenville, SC; Gerald V. Doyle, Immunicon, Huntingdon Valley, PA; and Robert B. Livingston, University of Arizona Cancer Center, Tucson, AZ.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Gralow
authors.affiliation: Jeffrey B. Smerage, Anne F. Schott, and Daniel F. Hayes, University of Michigan Comprehensive Cancer Center, Ann Arbor; Gordan Srkalovic, Sparrow Regional Cancer Center, Lansing; Sheela Tejwani, Henry Ford Hospital, Detroit, MI; William E. Barlow and Danika L. Lew, SWOG Statistical Center; Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA; Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston, TX; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Brian Leyland-Jones, Avera Cancer Institute, Sioux Falls, SD; Mark A. O'Rourke, Greenville Health System Cancer Institute/Greenville Community Clinical Oncology Program, Greenville, SC; Gerald V. Doyle, Immunicon, Huntingdon Valley, PA; and Robert B. Livingston, University of Arizona Cancer Center, Tucson, AZ.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Livingston
authors.affiliation: Jeffrey B. Smerage, Anne F. Schott, and Daniel F. Hayes, University of Michigan Comprehensive Cancer Center, Ann Arbor; Gordan Srkalovic, Sparrow Regional Cancer Center, Lansing; Sheela Tejwani, Henry Ford Hospital, Detroit, MI; William E. Barlow and Danika L. Lew, SWOG Statistical Center; Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA; Gabriel N. Hortobagyi, University of Texas MD Anderson Cancer Center, Houston, TX; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Brian Leyland-Jones, Avera Cancer Institute, Sioux Falls, SD; Mark A. O'Rourke, Greenville Health System Cancer Institute/Greenville Community Clinical Oncology Program, Greenville, SC; Gerald V. Doyle, Immunicon, Huntingdon Valley, PA; and Robert B. Livingston, University of Arizona Cancer Center, Tucson, AZ. hayesdf@umich.edu.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D057915:Drug Substitution; D005260:Female; D006801:Humans; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents