Breast Cancer Research and Treatment

, Volume 146, Issue 2, pp 235–244 | Cite as

Effect of multifocality and multicentricity on outcome in early stage breast cancer: a systematic review and meta-analysis

  • Francisco E. Vera-Badillo
  • Marc Napoleone
  • Alberto Ocana
  • Arnoud J. Templeton
  • Bostjan Seruga
  • Mustafa Al-Mubarak
  • Hashem AlHashem
  • Ian F. Tannock
  • Eitan AmirEmail author


Women with multifocal or multicentric breast tumors (multifocality henceforth) have been reported to have greater probability of nodal metastasis and relapse and worse survival than women with unifocal tumors. However, these associations have been inconsistent and multifocality is not taken into account by staging guidelines and prognostic models. A systematic review of electronic databases identified publications exploring the association between multifocality and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and loco-regional relapse (LRR). The hazard ratios (HRs) for OS and DFS for multifocal compared to unifocal tumors were extracted from multivariable analyses and included in a meta-analysis. For studies not reporting multivariable analyses, odds ratios (OR) were estimated from Kaplan–Meier curves for all endpoints at 5 and 10 years. Twenty-two studies comprising 67,557 women were included. Multifocality was reported in 9.5 % of patients. Classical prognostic factors were well balanced between unifocal and multifocal populations. In multivariable analyses, multifocality was associated with significantly worse OS (HR 1.65; P = 0.02), and a non-significant association with worse DFS (HR 1.96; P = 0.07). In univariable analyses, multifocality was associated with worse OS, DFS, DSS, and LRR at 5 years (OR 1.39, P = 0.02; OR 1.52, P = 0.02; OR 1.56, P = 0.03; and OR 3.23, P = 0.02, respectively). Similar estimates were observed at 10 years, but statistical significance was only reached for DSS and LRR. Mutifocality appears to be associated with a worse prognosis, however, substantial inter-study heterogeneity limits the precise determination of increased risk. Further validation of the independent prognostic impact of multifocality is warranted.


Breast cancer Multifocality/multicentricity Prognosis 



The authors would like to thank Junhui Zhang, information specialist at the Princess Margaret Cancer Centre Library, for her help with the database search.


This study was supported by Consejo Nacional de Ciencia y Tecnologia (CONACYT), Mexico (Ref: 214638) to FEV-B.

Conflict of interest

All authors disclose that they have no relevant conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Francisco E. Vera-Badillo
    • 1
    • 4
  • Marc Napoleone
    • 1
    • 4
  • Alberto Ocana
    • 2
  • Arnoud J. Templeton
    • 1
    • 4
  • Bostjan Seruga
    • 3
  • Mustafa Al-Mubarak
    • 1
    • 4
  • Hashem AlHashem
    • 1
    • 4
  • Ian F. Tannock
    • 1
    • 4
  • Eitan Amir
    • 1
    • 4
    Email author
  1. 1.Division of Medical Oncology & HematologyPrincess Margaret Cancer CentreTorontoCanada
  2. 2.Translational Research UnitAlbacete University HospitalAlbaceteSpain
  3. 3.Sector of Medical OncologyInstitute of Oncology LjubljanaLjubljanaSlovenia
  4. 4.Department of MedicineUniversity of TorontoTorontoCanada

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