Breast Cancer Research and Treatment

, Volume 143, Issue 2, pp 333–342 | Cite as

Near-infrared fluorescence sentinel lymph node mapping in breast cancer: a multicenter experience

  • Floris P. R. Verbeek
  • Susan L. Troyan
  • J. Sven D. Mieog
  • Gerrit-Jan Liefers
  • Lorissa A. Moffitt
  • Mireille Rosenberg
  • Judith Hirshfield-Bartek
  • Sylvain Gioux
  • Cornelis J. H. van de Velde
  • Alexander L. VahrmeijerEmail author
  • John V. Frangioni
Clinical Trial


Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has the potential to improve the sentinel lymph node (SLN) procedure by facilitating percutaneous and intraoperative identification of lymphatic channels and SLNs. Previous studies suggested that a dose of 0.62 mg (1.6 mL of 0.5 mM) ICG is optimal for SLN mapping in breast cancer. The aim of this study was to evaluate the diagnostic accuracy of NIR fluorescence for SLN mapping in breast cancer patients when used in conjunction with conventional techniques. Study subjects were 95 breast cancer patients planning to undergo SLN procedure at either the Dana-Farber/Harvard Cancer Center (Boston, MA, USA) or the Leiden University Medical Center (Leiden, the Netherlands) between July 2010 and January 2013. Subjects underwent the standard-of-care SLN procedure at each institution using 99Technetium-colloid in all subjects and patent blue in 27 (28 %) of the subjects. NIR fluorescence-guided SLN detection was performed using the Mini-FLARE imaging system. SLN identification was successful in 94 of 95 subjects (99 %) using NIR fluorescence imaging or a combination of both NIR fluorescence imaging and radioactive guidance. In 2 of 95 subjects, radioactive guidance was necessary for initial in vivo identification of SLNs. In 1 of 95 subjects, NIR fluorescence was necessary for initial in vivo identification of SLNs. A total of 177 SLNs (mean 1.9, range 1–5) were resected: 100 % NIR fluorescent, 88 % radioactive, and 78 % (of 40 nodes) blue. In 2 of 95 subjects (2.1 %), SLNs-containing macrometastases were found only by NIR fluorescence, and in one patient this led to upstaging to N1. This study demonstrates the safe and accurate application of NIR fluorescence imaging for the identification of SLNs in breast cancer patients, but calls into question what technique should be used as the gold standard in future studies.


Near-infrared fluorescence Breast cancer Sentinel lymph node mapping Indocyanine green 



The authors thank Alan Stockdale, Dr. Vivek Venugopal, Florin Neacsu, Frank W. Kettenring, Dr. Yoshitomo Ashitate, Dr. Summer Gibbs, and Yang (Allison) Xie for operation of the Mini-FLARE imaging system, and David J. Burrington, Jr. for editing. F.P.R. Verbeek’s travel to Boston for completion of the trials was sponsored by the Leiden University Fund/Piso Kuperus. J.S.D. Mieog is a MD-medical research trainee funded by The Netherlands Organization for Health Research and Development (Grant No. 92003526). This study was performed within the framework of the Centre for Translational Molecular Medicine, project MUSIS (grant 03O-202), and was funded by the Nuts Ohra Fund, Dutch Cancer Society grant UL2010-4732 and National Institutes of Health grants R21-CA-130297 and R01-CA-115296. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Conflict of interest

Floris P.R. Verbeek, Susan L. Troyan, J. Sven D. Mieog, Gerrit-Jan Liefers, Lorissa A. Moffitt, Mireille Rosenberg, Judith Hirshfield-Bartek, Sylvain Gioux, Cornelis J.H. van de Velde, Alexander L. Vahrmeijer: none. John V. Frangioni: FLARE™ technology is owned by the Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School. Dr. Frangioni has started three for-profit companies, Curadel, Curadel ResVet Imaging, and Curadel Surgical Innovations, which has optioned FLARE™ technology for potential licensing from Beth Israel Deaconess Medical Center.

Ethical standards

This study was approved separately by the Medical Ethics Committees of the Dana-Farber/Harvard Cancer Center (Boston, MA, USA) and the Leiden University Medical Center (Leiden, The Netherlands) and performed in accordance with the ethical standards of the Helsinki Declaration of 1975. All subjects gave informed consent and were anonymized.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Floris P. R. Verbeek
    • 1
  • Susan L. Troyan
    • 2
  • J. Sven D. Mieog
    • 1
  • Gerrit-Jan Liefers
    • 1
  • Lorissa A. Moffitt
    • 3
  • Mireille Rosenberg
    • 3
  • Judith Hirshfield-Bartek
    • 2
  • Sylvain Gioux
    • 3
  • Cornelis J. H. van de Velde
    • 1
  • Alexander L. Vahrmeijer
    • 1
    Email author
  • John V. Frangioni
    • 3
    • 4
  1. 1.Department of SurgeryLeiden University Medical CenterLeidenThe Netherlands
  2. 2.Department of SurgeryDana-Farber/Brigham and Women’s Cancer CenterBostonUSA
  3. 3.Division of Hematology/Oncology, Department of MedicineBeth Israel Deaconess Medical CenterBostonUSA
  4. 4.Department of RadiologyBeth Israel Deaconess Medical CenterBostonUSA

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