Long-term follow-up study of a prospective multicenter sentinel node trial: Molecular detection of breast cancer sentinel node metastases

Kathryn Mary Verbanac, Christopher Justus Min, Ann Elizabeth Mannie, Jianfen Lu, Kevin F. O'Brien, Martin Rosman, Lorraine Tafra

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalAnnals of Surgical Oncology
Volume17
Issue numberSUPPL. 3
DOIs
StatePublished - Oct 2010
Externally publishedYes

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Breast Neoplasms
Neoplasm Metastasis
Recurrence
Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
cyhalothrin
Survival
Sentinel Lymph Node
Research Ethics Committees
Hematoxylin
Eosine Yellowish-(YS)
Immunohistochemistry
Odds Ratio
Confidence Intervals
Pathology
Staining and Labeling
Neoplasms

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Long-term follow-up study of a prospective multicenter sentinel node trial : Molecular detection of breast cancer sentinel node metastases. / Verbanac, Kathryn Mary; Min, Christopher Justus; Mannie, Ann Elizabeth; Lu, Jianfen; O'Brien, Kevin F.; Rosman, Martin; Tafra, Lorraine.

In: Annals of Surgical Oncology, Vol. 17, No. SUPPL. 3, 10.2010.

Research output: Contribution to journalArticle

Verbanac, Kathryn Mary ; Min, Christopher Justus ; Mannie, Ann Elizabeth ; Lu, Jianfen ; O'Brien, Kevin F. ; Rosman, Martin ; Tafra, Lorraine. / Long-term follow-up study of a prospective multicenter sentinel node trial : Molecular detection of breast cancer sentinel node metastases. In: Annals of Surgical Oncology. 2010 ; Vol. 17, No. SUPPL. 3.
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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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T2 - Molecular detection of breast cancer sentinel node metastases

AU - Verbanac, Kathryn Mary

AU - Min, Christopher Justus

AU - Mannie, Ann Elizabeth

AU - Lu, Jianfen

AU - O'Brien, Kevin F.

AU - Rosman, Martin

AU - Tafra, Lorraine

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AB - 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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