Molecular detection of micrometastatic breast cancer in histopathology-negative axillary lymph nodes correlates with traditional predictors of prognosis: An interim analysis of a prospective multi-institutional cohort study

William E. Gillanders, Kaidi Mikhitarian, Renee Hebert, Patrick D. Mauldin, Yuko Palesch, Kenneth C Walters, Marshall M. Urist, G. Bruce Mann, Gerard Doherty, Virginia M. Herrmann, Arnold D. Hill, Oleg Eremin, Mohamed El-Sheemy, Richard K. Orr, Alvaro A. Valle, Michael A. Henderson, Robert L. Dewitty, Sonia L. Sugg, Eric Frykberg, Karen YehRichard M. Bell, John S. Metcalf, Bruce M. Elliott, Thomas Brothers, Jay Robison, Michael Mitas, David J. Cole, Kirby I. Bland, R. Daniel Beauchamp, Henry M. Kuerer, William C. Wood, Michael J. Edwards, Roger R. Perry

Research output: Contribution to journalArticle

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Abstract

Objective: We sought to establish the clinical relevance of micrometastatic disease detected by reverse transcription polymerase chain reaction (RT-PCR) in axillary lymph nodes (ALN) of breast cancer patients. Background: The presence of ALN metastases remains one of the most valuable prognostic indicators in women with breast cancer. However, the clinical relevance of molecular detection of micrometastatic breast cancer in sentinel lymph nodes (SLN) and non-sentinel ALN has not been established. Methods: Four hundred eighty-nine patients with T1-T3 primary breast cancers were analyzed in a prospective, multi-institutional cohort study. ALN were analyzed by standard histopathology (H&E staining) and by multimarker, real-time RT-PCR analysis (mam, mamB, muc1, CEA, PSE, CK19, and PIP) designed to detect breast cancer micrometastases. Results: A positive marker signal was observed in 126 (87%) of 145 subjects with pathology-positive ALN, and in 112 (33%) of 344 subjects with pathology-negative ALN. In subjects with pathology-negative ALN, a positive marker signal was significantly associated with traditional indicators of prognosis, such as histologic grade (P = 0.0255) and St. Gallen risk category (P = 0.022). Mammaglobin was the most informative marker in the panel. Conclusion: This is the first report to show that overexpression of breast cancer-associated genes in breast cancer subjects with pathology-negative ALN correlates with traditional indicators of disease prognosis. These interim results provide strong evidence that molecular markers could serve as valid surrogates for the detection of occult micrometastases in ALN. Correlation of real-time RT-PCR analyses with disease-free survival in this patient cohort will help to define the clinical relevance of micrometastatic disease in this patient population.

Original languageEnglish (US)
Pages (from-to)828-840
Number of pages13
JournalAnnals of Surgery
Volume239
Issue number6
DOIs
StatePublished - Jun 1 2004

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Cohort Studies
Lymph Nodes
Breast Neoplasms
Pathology
Reverse Transcription
Neoplasm Micrometastasis
Polymerase Chain Reaction
Neoplasm Genes
Disease-Free Survival
Staining and Labeling
Neoplasm Metastasis
Population

ASJC Scopus subject areas

  • Surgery

Cite this

Molecular detection of micrometastatic breast cancer in histopathology-negative axillary lymph nodes correlates with traditional predictors of prognosis : An interim analysis of a prospective multi-institutional cohort study. / Gillanders, William E.; Mikhitarian, Kaidi; Hebert, Renee; Mauldin, Patrick D.; Palesch, Yuko; Walters, Kenneth C; Urist, Marshall M.; Mann, G. Bruce; Doherty, Gerard; Herrmann, Virginia M.; Hill, Arnold D.; Eremin, Oleg; El-Sheemy, Mohamed; Orr, Richard K.; Valle, Alvaro A.; Henderson, Michael A.; Dewitty, Robert L.; Sugg, Sonia L.; Frykberg, Eric; Yeh, Karen; Bell, Richard M.; Metcalf, John S.; Elliott, Bruce M.; Brothers, Thomas; Robison, Jay; Mitas, Michael; Cole, David J.; Bland, Kirby I.; Beauchamp, R. Daniel; Kuerer, Henry M.; Wood, William C.; Edwards, Michael J.; Perry, Roger R.

In: Annals of Surgery, Vol. 239, No. 6, 01.06.2004, p. 828-840.

Research output: Contribution to journalArticle

Gillanders, WE, Mikhitarian, K, Hebert, R, Mauldin, PD, Palesch, Y, Walters, KC, Urist, MM, Mann, GB, Doherty, G, Herrmann, VM, Hill, AD, Eremin, O, El-Sheemy, M, Orr, RK, Valle, AA, Henderson, MA, Dewitty, RL, Sugg, SL, Frykberg, E, Yeh, K, Bell, RM, Metcalf, JS, Elliott, BM, Brothers, T, Robison, J, Mitas, M, Cole, DJ, Bland, KI, Beauchamp, RD, Kuerer, HM, Wood, WC, Edwards, MJ & Perry, RR 2004, 'Molecular detection of micrometastatic breast cancer in histopathology-negative axillary lymph nodes correlates with traditional predictors of prognosis: An interim analysis of a prospective multi-institutional cohort study', Annals of Surgery, vol. 239, no. 6, pp. 828-840. https://doi.org/10.1097/01.sla.0000128687.59439.d6
Gillanders, William E. ; Mikhitarian, Kaidi ; Hebert, Renee ; Mauldin, Patrick D. ; Palesch, Yuko ; Walters, Kenneth C ; Urist, Marshall M. ; Mann, G. Bruce ; Doherty, Gerard ; Herrmann, Virginia M. ; Hill, Arnold D. ; Eremin, Oleg ; El-Sheemy, Mohamed ; Orr, Richard K. ; Valle, Alvaro A. ; Henderson, Michael A. ; Dewitty, Robert L. ; Sugg, Sonia L. ; Frykberg, Eric ; Yeh, Karen ; Bell, Richard M. ; Metcalf, John S. ; Elliott, Bruce M. ; Brothers, Thomas ; Robison, Jay ; Mitas, Michael ; Cole, David J. ; Bland, Kirby I. ; Beauchamp, R. Daniel ; Kuerer, Henry M. ; Wood, William C. ; Edwards, Michael J. ; Perry, Roger R. / Molecular detection of micrometastatic breast cancer in histopathology-negative axillary lymph nodes correlates with traditional predictors of prognosis : An interim analysis of a prospective multi-institutional cohort study. In: Annals of Surgery. 2004 ; Vol. 239, No. 6. pp. 828-840.
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title = "Molecular detection of micrometastatic breast cancer in histopathology-negative axillary lymph nodes correlates with traditional predictors of prognosis: An interim analysis of a prospective multi-institutional cohort study",
abstract = "Objective: We sought to establish the clinical relevance of micrometastatic disease detected by reverse transcription polymerase chain reaction (RT-PCR) in axillary lymph nodes (ALN) of breast cancer patients. Background: The presence of ALN metastases remains one of the most valuable prognostic indicators in women with breast cancer. However, the clinical relevance of molecular detection of micrometastatic breast cancer in sentinel lymph nodes (SLN) and non-sentinel ALN has not been established. Methods: Four hundred eighty-nine patients with T1-T3 primary breast cancers were analyzed in a prospective, multi-institutional cohort study. ALN were analyzed by standard histopathology (H&E staining) and by multimarker, real-time RT-PCR analysis (mam, mamB, muc1, CEA, PSE, CK19, and PIP) designed to detect breast cancer micrometastases. Results: A positive marker signal was observed in 126 (87{\%}) of 145 subjects with pathology-positive ALN, and in 112 (33{\%}) of 344 subjects with pathology-negative ALN. In subjects with pathology-negative ALN, a positive marker signal was significantly associated with traditional indicators of prognosis, such as histologic grade (P = 0.0255) and St. Gallen risk category (P = 0.022). Mammaglobin was the most informative marker in the panel. Conclusion: This is the first report to show that overexpression of breast cancer-associated genes in breast cancer subjects with pathology-negative ALN correlates with traditional indicators of disease prognosis. These interim results provide strong evidence that molecular markers could serve as valid surrogates for the detection of occult micrometastases in ALN. Correlation of real-time RT-PCR analyses with disease-free survival in this patient cohort will help to define the clinical relevance of micrometastatic disease in this patient population.",
author = "Gillanders, {William E.} and Kaidi Mikhitarian and Renee Hebert and Mauldin, {Patrick D.} and Yuko Palesch and Walters, {Kenneth C} and Urist, {Marshall M.} and Mann, {G. Bruce} and Gerard Doherty and Herrmann, {Virginia M.} and Hill, {Arnold D.} and Oleg Eremin and Mohamed El-Sheemy and Orr, {Richard K.} and Valle, {Alvaro A.} and Henderson, {Michael A.} and Dewitty, {Robert L.} and Sugg, {Sonia L.} and Eric Frykberg and Karen Yeh and Bell, {Richard M.} and Metcalf, {John S.} and Elliott, {Bruce M.} and Thomas Brothers and Jay Robison and Michael Mitas and Cole, {David J.} and Bland, {Kirby I.} and Beauchamp, {R. Daniel} and Kuerer, {Henry M.} and Wood, {William C.} and Edwards, {Michael J.} and Perry, {Roger R.}",
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TY - JOUR

T1 - Molecular detection of micrometastatic breast cancer in histopathology-negative axillary lymph nodes correlates with traditional predictors of prognosis

T2 - An interim analysis of a prospective multi-institutional cohort study

AU - Gillanders, William E.

AU - Mikhitarian, Kaidi

AU - Hebert, Renee

AU - Mauldin, Patrick D.

AU - Palesch, Yuko

AU - Walters, Kenneth C

AU - Urist, Marshall M.

AU - Mann, G. Bruce

AU - Doherty, Gerard

AU - Herrmann, Virginia M.

AU - Hill, Arnold D.

AU - Eremin, Oleg

AU - El-Sheemy, Mohamed

AU - Orr, Richard K.

AU - Valle, Alvaro A.

AU - Henderson, Michael A.

AU - Dewitty, Robert L.

AU - Sugg, Sonia L.

AU - Frykberg, Eric

AU - Yeh, Karen

AU - Bell, Richard M.

AU - Metcalf, John S.

AU - Elliott, Bruce M.

AU - Brothers, Thomas

AU - Robison, Jay

AU - Mitas, Michael

AU - Cole, David J.

AU - Bland, Kirby I.

AU - Beauchamp, R. Daniel

AU - Kuerer, Henry M.

AU - Wood, William C.

AU - Edwards, Michael J.

AU - Perry, Roger R.

PY - 2004/6/1

Y1 - 2004/6/1

N2 - Objective: We sought to establish the clinical relevance of micrometastatic disease detected by reverse transcription polymerase chain reaction (RT-PCR) in axillary lymph nodes (ALN) of breast cancer patients. Background: The presence of ALN metastases remains one of the most valuable prognostic indicators in women with breast cancer. However, the clinical relevance of molecular detection of micrometastatic breast cancer in sentinel lymph nodes (SLN) and non-sentinel ALN has not been established. Methods: Four hundred eighty-nine patients with T1-T3 primary breast cancers were analyzed in a prospective, multi-institutional cohort study. ALN were analyzed by standard histopathology (H&E staining) and by multimarker, real-time RT-PCR analysis (mam, mamB, muc1, CEA, PSE, CK19, and PIP) designed to detect breast cancer micrometastases. Results: A positive marker signal was observed in 126 (87%) of 145 subjects with pathology-positive ALN, and in 112 (33%) of 344 subjects with pathology-negative ALN. In subjects with pathology-negative ALN, a positive marker signal was significantly associated with traditional indicators of prognosis, such as histologic grade (P = 0.0255) and St. Gallen risk category (P = 0.022). Mammaglobin was the most informative marker in the panel. Conclusion: This is the first report to show that overexpression of breast cancer-associated genes in breast cancer subjects with pathology-negative ALN correlates with traditional indicators of disease prognosis. These interim results provide strong evidence that molecular markers could serve as valid surrogates for the detection of occult micrometastases in ALN. Correlation of real-time RT-PCR analyses with disease-free survival in this patient cohort will help to define the clinical relevance of micrometastatic disease in this patient population.

AB - Objective: We sought to establish the clinical relevance of micrometastatic disease detected by reverse transcription polymerase chain reaction (RT-PCR) in axillary lymph nodes (ALN) of breast cancer patients. Background: The presence of ALN metastases remains one of the most valuable prognostic indicators in women with breast cancer. However, the clinical relevance of molecular detection of micrometastatic breast cancer in sentinel lymph nodes (SLN) and non-sentinel ALN has not been established. Methods: Four hundred eighty-nine patients with T1-T3 primary breast cancers were analyzed in a prospective, multi-institutional cohort study. ALN were analyzed by standard histopathology (H&E staining) and by multimarker, real-time RT-PCR analysis (mam, mamB, muc1, CEA, PSE, CK19, and PIP) designed to detect breast cancer micrometastases. Results: A positive marker signal was observed in 126 (87%) of 145 subjects with pathology-positive ALN, and in 112 (33%) of 344 subjects with pathology-negative ALN. In subjects with pathology-negative ALN, a positive marker signal was significantly associated with traditional indicators of prognosis, such as histologic grade (P = 0.0255) and St. Gallen risk category (P = 0.022). Mammaglobin was the most informative marker in the panel. Conclusion: This is the first report to show that overexpression of breast cancer-associated genes in breast cancer subjects with pathology-negative ALN correlates with traditional indicators of disease prognosis. These interim results provide strong evidence that molecular markers could serve as valid surrogates for the detection of occult micrometastases in ALN. Correlation of real-time RT-PCR analyses with disease-free survival in this patient cohort will help to define the clinical relevance of micrometastatic disease in this patient population.

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