title: A pooled analysis of bone marrow micrometastasis in breast cancer.
abstract: BACKGROUND
  We assessed the prognostic significance of the presence of micrometastasis in the bone marrow at the time of diagnosis of breast cancer by means of a pooled analysis.
  
  
  METHODS
  We combined individual patient data from nine studies involving 4703 patients with stage I, II, or III breast cancer. We evaluated patient outcomes over a 10-year follow-up period (median, 5.2 years), using a multivariable piecewise Cox regression model.
  
  
  RESULTS
  Micrometastasis was detected in 30.6 percent of the patients. As compared with women without bone marrow micrometastasis, patients with bone marrow micrometastasis had larger tumors and tumors with a higher histologic grade and more often had lymph-node metastases and hormone receptor-negative tumors (P<0.001 for all variables). The presence of micrometastasis was a significant prognostic factor with respect to poor overall survival and breast-cancer-specific survival (univariate mortality ratios, 2.15 and 2.44, respectively; P<0.001 for both outcomes) and poor disease-free survival and distant-disease-free survival during the 10-year observation period (incidence-rate ratios, 2.13 and 2.33, respectively; P<0.001 for both outcomes). In the multivariable analysis, micrometastasis was an independent predictor of a poor outcome. In the univariate subgroup analysis, breast-cancer-specific survival among patients with micrometastasis was significantly shortened (P<0.001 for all comparisons) among those receiving adjuvant endocrine treatment (mortality ratio, 3.22) or cytotoxic therapy (mortality ratio, 2.32) and among patients who had tumors no larger than 2 cm in diameter without lymph-node metastasis and who did not receive systemic adjuvant therapy (mortality ratio, 3.65).
  
  
  CONCLUSIONS
  The presence of micrometastasis in the bone marrow at the time of diagnosis of breast cancer is associated with a poor prognosis.
authors.affiliation: Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria. stephan.braun@uklibk.ac.at
authors.forename: Stephan
authors.initials: S
authors.lastname: Braun
authors.forename: Florian D
authors.initials: FD
authors.lastname: Vogl
authors.forename: Bjørn
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authors.lastname: Naume
authors.forename: Wolfgang
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authors.lastname: Janni
authors.forename: Michael P
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authors.forename: R Charles
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authors.forename: Günter
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authors.lastname: Schlimok
authors.forename: Ingo J
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authors.forename: Bernd
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authors.forename: Jean-Yves
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authors.forename: Christian
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authors.lastname: Marth
authors.forename: Daniel
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authors.lastname: Oruzio
authors.forename: Gro
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authors.lastname: Wiedswang
authors.forename: Erich-Franz
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authors.lastname: Solomayer
authors.forename: Günther
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authors.lastname: Kundt
authors.forename: Barbara
authors.initials: B
authors.lastname: Strobl
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: George Y C
authors.initials: GY
authors.lastname: Wong
authors.forename: Judith
authors.initials: J
authors.lastname: Bliss
authors.forename: Anne
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authors.lastname: Vincent-Salomon
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
mesh_terms: D019046:Bone Marrow Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis