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Long-Term Follow-up Study of a Prospective Multicenter Sentinel Node Trial: Molecular Detection of Breast Cancer Sentinel Node Metastases

  • American Society of Breast Surgeons
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

This prospective multicenter sentinel lymph node (SLN) trial investigated whether molecular analysis would improve the detection of SLN metastases and their prognostic value. We report mammaglobin quantitative real-time polymerase chain reaction (qRT-PCR) results and clinical outcome for 547 patients (mean follow-up 7 years).

Methods

Breast cancer patients (excluding stage IV disease or palpable nodes) were enrolled from 1996 to 2005 at 16 institutional review board-approved sites. Alternate 2-mm serial sections of each SLN were examined by hematoxylin and eosin staining with or without immunohistochemistry at multiple levels or blinded and assayed by Taqman qRT-PCR according to previously established thresholds.

Results

Mammaglobin remains a highly specific (99%), sensitive (97% primary tumor; 82% N1 SLN) marker for breast cancer. Mammaglobin SLN expression was associated with other prognostic factors, was detected in most patients with distant recurrence (48 of 79; 61%), and was associated with decreased recurrence-free survival (log rank P < 0.0001). Molecular analysis upstaged 13% (52 of 394) node-negative (N0) patients who exhibited a significantly lower distant recurrence-free survival compared to node-negative, PCR-negative patients (80 vs. 91%; P < 0.04). N0 patients with PCR-positive SLN were 3.4 times more likely to experience relapse than PCR-negative patients (odds ratio 3.4; 95% confidence interval 1.6–7.1; P = 0.001). However, molecular staging failed to predict most of the N0 patient recurrences (25 of 34) and was not a statistically significant independent predictor of distant recurrence.

Conclusions

To our knowledge, these data are the first to prospectively compare PCR detection of SLN metastases with long-term outcome in breast cancer patients. Molecular staging of SLN detected clinically significant disease missed by standard pathology. Further refinement and optimization of molecular staging is indicated to improve clinical utility.

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Acknowledgment

This study was supported in part by a career development award (DAMD 7-98-1-8079) and a clinical translation research award from the Department of Defense Breast Cancer Research program (DAMD 17-00-1-0239). We acknowledge a research contract from Ortho Clinical Diagnostics. We acknowledge the technical and collaborative support of Drs. John Backus, Robert Belly, David Atkins, and colleagues, Veridex, LLC. We acknowledge the technical assistance of H. Keith Pittman, BS, Meagan Holcomb, MS, Rith Yim, MS, and Khalief Hamden, MD, East Carolina University. We acknowledge the database management of Kristen Sawyer, MS, CCRA, and Maryann Moreland, BA, Anne Arundel Medical Center; Diane Boyce, RN, Debra Peaden, CCRP, and Anna Broome, BA, East Carolina University. We also acknowledge the support of the East Carolina University/Anne Arundel Medical Center Sentinel Node Study Group Investigators and Sites (Eastern Virginia University/Sentara Norfolk General Hospital, Norfolk, VA; Winchester Hospital, Woburn, MA; Carteret Surgical, Morehead City, NC; Martha Jefferson Hospital, Charlottesville, VA; Alamance Regional Medical Center, Burlington, NC; Memorial Hospital, Martinsville, VA; Carolinas Medical Center, Charlotte, NC; Moore Regional Hospital, Pinehurst, NC; Mercy Hospital, Portland, ME; Breast Care Center of the Blue Ridge, Roanoke, VA; Virginia Beach General Hospital, Virginia Beach, VA; Moses Cone Hospital, Greensboro, NC; Lewis Gale Clinic, Salem, VA; Winchester Medical Center, Winchester, VA).

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Authors and Affiliations

  1. Department of Surgery, The Brody School of Medicine at East Carolina University, Greenville, NC, USA

    Kathryn Mary Verbanac PhD, Christopher Justus Min MD, Ann Elizabeth Mannie PhD & Jianfen Lu MS

  2. The College of Allied Health Sciences, East Carolina University, Greenville, NC, USA

    Kevin F. O’Brien PhD

  3. The Breast Center at Anne Arundel Medical Center, Annapolis, MD, USA

    Martin Rosman MD & Lorraine Tafra MD

Authors
  1. Kathryn Mary Verbanac PhD
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  2. Christopher Justus Min MD
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  3. Ann Elizabeth Mannie PhD
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  4. Jianfen Lu MS
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  5. Kevin F. O’Brien PhD
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  6. Martin Rosman MD
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  7. Lorraine Tafra MD
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Consortia

for the ECU/AAMC Sentinel Node Study Group

Corresponding author

Correspondence to Kathryn Mary Verbanac PhD.

Additional information

This study is conducted for the ECU/AAMC Sentinel Node Study Group.

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Verbanac, K.M., Min, C.J., Mannie, A.E. et al. Long-Term Follow-up Study of a Prospective Multicenter Sentinel Node Trial: Molecular Detection of Breast Cancer Sentinel Node Metastases. Ann Surg Oncol 17 (Suppl 3), 368–377 (2010). https://doi.org/10.1245/s10434-010-1262-2

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  • DOI: https://doi.org/10.1245/s10434-010-1262-2

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