Circulating tumor cells, disease progression, and survival in metastatic breast cancer

Massimo Cristofanilli, G. Thomas Budd, Matthew J. Ellis, Alison T Stopeck, Jeri Matera, M. Craig Miller, James M. Reuben, Gerald V. Doyle, W. Jeffrey Allard, Leon W M M Terstappen, Daniel F. Hayes

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Abstract

BACKGROUND: We tested the hypothesis that the level of circulating tumor cells can predict survival in metastatic breast cancer. METHODS: In a prospective, multicenter study, we tested 177 patients with measurable metastatic breast cancer for levels of circulating tumor cells both before the patients were to start a new line of treatment and at the first follow-up visit. The progression of the disease or the response to treatment was determined with the use of standard imaging studies at the participating centers. RESULTS: Outcomes were assessed according to levels of circulating tumor cells at baseline, before the patients started a new treatment for metastatic disease. Patients in a training set with levels of circulating tumor cells equal to or higher than 5 per 7.5 ml of whole blood, as compared with the group with fewer than 5 circulating tumor cells per 7.5 ml, had a shorter median progression-free survival (2.7 months vs. 7.0 months, P<0.001) and shorter overall survival (10.1 months vs. >18 months, P<0.001). At the first follow-up visit after the initiation of therapy, this difference between the groups persisted (progression-free survival, 2.1 months vs. 7.0 months; P<0.001; overall survival, 8.2 months vs. >18 months; P<0.001), and the reduced proportion of patients (from 49 percent to 30 percent) in the group with an unfavorable prognosis suggested that there was a benefit from therapy. The multivariate Cox proportional-hazards regression showed that, of all the variables in the statistical model, the levels of circulating tumor cells at baseline and at the first follow-up visit were the most significant predictors of progression-free and overall survival. CONCLUSIONS: The number of circulating tumor cells before treatment is an independent predictor of progression-free survival and overall survival in patients with metastatic breast cancer.

Original languageEnglish (US)
Pages (from-to)781-791
Number of pages11
JournalNew England Journal of Medicine
Volume351
Issue number8
DOIs
StatePublished - Aug 19 2004

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Circulating Neoplastic Cells
Disease Progression
Breast Neoplasms
Survival
Disease-Free Survival
Therapeutics
Statistical Models
Multicenter Studies
Prospective Studies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cristofanilli, M., Budd, G. T., Ellis, M. J., Stopeck, A. T., Matera, J., Miller, M. C., ... Hayes, D. F. (2004). Circulating tumor cells, disease progression, and survival in metastatic breast cancer. New England Journal of Medicine, 351(8), 781-791. https://doi.org/10.1056/NEJMoa040766

Circulating tumor cells, disease progression, and survival in metastatic breast cancer. / Cristofanilli, Massimo; Budd, G. Thomas; Ellis, Matthew J.; Stopeck, Alison T; Matera, Jeri; Miller, M. Craig; Reuben, James M.; Doyle, Gerald V.; Allard, W. Jeffrey; Terstappen, Leon W M M; Hayes, Daniel F.

In: New England Journal of Medicine, Vol. 351, No. 8, 19.08.2004, p. 781-791.

Research output: Contribution to journalArticle

Cristofanilli, M, Budd, GT, Ellis, MJ, Stopeck, AT, Matera, J, Miller, MC, Reuben, JM, Doyle, GV, Allard, WJ, Terstappen, LWMM & Hayes, DF 2004, 'Circulating tumor cells, disease progression, and survival in metastatic breast cancer', New England Journal of Medicine, vol. 351, no. 8, pp. 781-791. https://doi.org/10.1056/NEJMoa040766
Cristofanilli, Massimo ; Budd, G. Thomas ; Ellis, Matthew J. ; Stopeck, Alison T ; Matera, Jeri ; Miller, M. Craig ; Reuben, James M. ; Doyle, Gerald V. ; Allard, W. Jeffrey ; Terstappen, Leon W M M ; Hayes, Daniel F. / Circulating tumor cells, disease progression, and survival in metastatic breast cancer. In: New England Journal of Medicine. 2004 ; Vol. 351, No. 8. pp. 781-791.
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AU - Cristofanilli, Massimo

AU - Budd, G. Thomas

AU - Ellis, Matthew J.

AU - Stopeck, Alison T

AU - Matera, Jeri

AU - Miller, M. Craig

AU - Reuben, James M.

AU - Doyle, Gerald V.

AU - Allard, W. Jeffrey

AU - Terstappen, Leon W M M

AU - Hayes, Daniel F.

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N2 - BACKGROUND: We tested the hypothesis that the level of circulating tumor cells can predict survival in metastatic breast cancer. METHODS: In a prospective, multicenter study, we tested 177 patients with measurable metastatic breast cancer for levels of circulating tumor cells both before the patients were to start a new line of treatment and at the first follow-up visit. The progression of the disease or the response to treatment was determined with the use of standard imaging studies at the participating centers. RESULTS: Outcomes were assessed according to levels of circulating tumor cells at baseline, before the patients started a new treatment for metastatic disease. Patients in a training set with levels of circulating tumor cells equal to or higher than 5 per 7.5 ml of whole blood, as compared with the group with fewer than 5 circulating tumor cells per 7.5 ml, had a shorter median progression-free survival (2.7 months vs. 7.0 months, P<0.001) and shorter overall survival (10.1 months vs. >18 months, P<0.001). At the first follow-up visit after the initiation of therapy, this difference between the groups persisted (progression-free survival, 2.1 months vs. 7.0 months; P<0.001; overall survival, 8.2 months vs. >18 months; P<0.001), and the reduced proportion of patients (from 49 percent to 30 percent) in the group with an unfavorable prognosis suggested that there was a benefit from therapy. The multivariate Cox proportional-hazards regression showed that, of all the variables in the statistical model, the levels of circulating tumor cells at baseline and at the first follow-up visit were the most significant predictors of progression-free and overall survival. CONCLUSIONS: The number of circulating tumor cells before treatment is an independent predictor of progression-free survival and overall survival in patients with metastatic breast cancer.

AB - BACKGROUND: We tested the hypothesis that the level of circulating tumor cells can predict survival in metastatic breast cancer. METHODS: In a prospective, multicenter study, we tested 177 patients with measurable metastatic breast cancer for levels of circulating tumor cells both before the patients were to start a new line of treatment and at the first follow-up visit. The progression of the disease or the response to treatment was determined with the use of standard imaging studies at the participating centers. RESULTS: Outcomes were assessed according to levels of circulating tumor cells at baseline, before the patients started a new treatment for metastatic disease. Patients in a training set with levels of circulating tumor cells equal to or higher than 5 per 7.5 ml of whole blood, as compared with the group with fewer than 5 circulating tumor cells per 7.5 ml, had a shorter median progression-free survival (2.7 months vs. 7.0 months, P<0.001) and shorter overall survival (10.1 months vs. >18 months, P<0.001). At the first follow-up visit after the initiation of therapy, this difference between the groups persisted (progression-free survival, 2.1 months vs. 7.0 months; P<0.001; overall survival, 8.2 months vs. >18 months; P<0.001), and the reduced proportion of patients (from 49 percent to 30 percent) in the group with an unfavorable prognosis suggested that there was a benefit from therapy. The multivariate Cox proportional-hazards regression showed that, of all the variables in the statistical model, the levels of circulating tumor cells at baseline and at the first follow-up visit were the most significant predictors of progression-free and overall survival. CONCLUSIONS: The number of circulating tumor cells before treatment is an independent predictor of progression-free survival and overall survival in patients with metastatic breast cancer.

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