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Molecular Detection of Micrometastatic Breast Cancer in Histopathology—Negative Axillary Lymph Nodes Fails to Predict Breast Cancer Recurrence: A Final Analysis of a Prospective Multi-Institutional Cohort Study

Annals of Surgical Oncology volume 17, pages 312–320 (2010)Cite this article

Abstract

Background

To address the clinical relevance of molecular detection of occult breast cancer in sentinel lymph nodes and nonsentinel axillary lymph nodes (ALN), we initiated the Minimally Invasive Molecular Staging of Breast Cancer (MIMS) trial, a multi-institutional prospective cohort study. This trial represents the first prospective cohort study in which a multimarker, real-time reverse transcription polymerase chain reaction (RT-PCR) analysis was applied to the detection of breast cancer micrometastases in ALN.

Materials and Methods

Sentinel and/or nonsentinel ALN from 501 breast cancer subjects with T1–T3 primary tumors were analyzed by standard histopathology and multimarker, real-time RT-PCR analysis. Seven breast cancer-associated genes (mam, mamB, PIP, CK19, muc1, PSE, and CEA) known to be overexpressed in metastatic breast cancer compared with control lymph nodes were used. Follow-up data were collected for 5 years.

Results

Of the 501 breast cancer subjects enrolled, 348 were node negative and completed the 5-year follow-up. Of these patients (n = 94), 27% demonstrated evidence of molecular overexpression. The 5-year relapse-free survival rate was 95.4% (95% confidence interval [95% CI], 92.4–97.2%). No single gene or combination of study genes was predictive of recurrence.

Conclusions

The genes in this study panel failed to be predictive of clinical relapse. This may be a function of several factors: the low event rate at 5 years, the particular gene set, the methodology used for detection/analysis or that our original hypothesis was wrong and that the presence of positive marker signal by real-time RT-PCR is not associated with a worsened clinical outcome.

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Author information

Affiliations

  1. Department of Hematology and Oncology, Medical University of South Carolina, Charleston, SC, USA

    Michael Mitas PhD

  2. Department of Surgery, Medical University of South Carolina, Charleston, SC, USA

    Carla Suzanne Fisher MD, David J. Cole MD, Virginia M. Herrmann MD & Megan K. Baker MD

  3. Department of Biostatistics, Medical University of South Carolina, Charleston, SC, USA

    Elizabeth Garrett-Meyer PhD

  4. Department of Pathology, Medical University of South Carolina, Charleston, SC, USA

    John S. Metcalf MD

  5. Department of Surgery, Washington University, St. Louis, MO, USA

    William E. Gillanders MD

  6. Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, USA

    Kaidi Mikhitarian MD

  7. Department of Surgery, University of Alabama, Birmingham, AL, USA

    Marshall M. Urist MD

  8. Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia

    G. Bruce Mann MD

  9. Department of Surgery, University of Michigan, Ann Arbor, MI, USA

    Gerard Doherty MD

  10. Department of Surgery, Beaumont Hospital, Dublin, Ireland

    Virginia M. Herrmann MD & Arnold D. Hill MD

  11. Department of Surgery, Lincoln County Hospital, Lincoln, England, UK

    Oleg Eremin MD & Mohamed El-Sheemy MD, PhD

  12. Gibbs Regional Cancer Center, Spartanburg, SC, USA

    Richard K. Orr MD

  13. Department of Surgery, University of Tennessee, Chattanooga, TN, USA

    Alvaro A. Valle MD

  14. Department of Surgery, St. Vincent’s Hospital, Fitzroy, VIC, Australia

    Michael A. Henderson MD

  15. Howard University Cancer Center, Washington, DC, USA

    Robert L. Dewitty MD

  16. Department of Surgery, University of Iowa, Iowa City, IA, USA

    Sonia L. Sugg MD

  17. Department of Surgery, University of Florida, Jacksonville, FL, USA

    Eric Frykberg MD

  18. Department of Surgery, Medical College of Georgia, Augusta, GA, USA

    Karen Yeh MD

  19. Department of Surgery, University of South Carolina, Columbia, SC, USA

    Richard M. Bell MD

Authors
  1. Carla Suzanne Fisher MD
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  2. David J. Cole MD
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  3. Michael Mitas PhD
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  4. Elizabeth Garrett-Meyer PhD
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  5. John S. Metcalf MD
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  6. William E. Gillanders MD
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  7. Kaidi Mikhitarian MD
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  8. Marshall M. Urist MD
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  9. G. Bruce Mann MD
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  10. Gerard Doherty MD
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  11. Virginia M. Herrmann MD
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  12. Arnold D. Hill MD
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  13. Oleg Eremin MD
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  14. Mohamed El-Sheemy MD, PhD
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  15. Richard K. Orr MD
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  16. Alvaro A. Valle MD
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  17. Michael A. Henderson MD
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  18. Robert L. Dewitty MD
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  19. Sonia L. Sugg MD
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  20. Eric Frykberg MD
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  21. Karen Yeh MD
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  22. Richard M. Bell MD
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  23. Megan K. Baker MD
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Corresponding author

Correspondence to Carla Suzanne Fisher MD.

Additional information

This study was support by the grant from Department of Defense N00014-99-1-0784.

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Fisher, C.S., Cole, D.J., Mitas, M. et al. Molecular Detection of Micrometastatic Breast Cancer in Histopathology—Negative Axillary Lymph Nodes Fails to Predict Breast Cancer Recurrence: A Final Analysis of a Prospective Multi-Institutional Cohort Study. Ann Surg Oncol 17, 312–320 (2010). https://doi.org/10.1245/s10434-010-1258-y

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  • DOI: https://doi.org/10.1245/s10434-010-1258-y

Keywords

  • Breast Cancer
  • Sentinel Lymph Node
  • Sentinel Lymph Node Biopsy
  • Reverse Transcription Polymerase Chain Reaction
  • Axillary Lymph Node