Does breast tumor heterogeneity necessitate further immunohistochemical staining on surgical specimens?

Lauren T. Greer, Martin Rosman, W. Charles Mylander, Jeffrey Hooke, Albert Kovatich, Kristen Sawyer, Robert R. Buras, Craig D. Shriver, Lorraine Tafra

Research output: Contribution to journalArticle

Abstract

Background: Prognostic and predictive tumor markers in breast cancer are most commonly performed on core needle biopsies (CNB) of the primary tumor. Because treatment recommendations are influenced by these markers, it is imperative to verify strong concordance between tumor markers on CNB specimens and the corresponding surgical specimens (SS). Study Design: A prospective study was performed on 165 women (205 samples) with breast cancer diagnosed from January 2009 to July 2011. Tumor type, grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki67 expression by immunohistochemical (IHC) testing were retrospectively analyzed in the CNB and SS. Contingency tables and agreement modeling were performed. Results: There was substantial agreement between the CNB and SS for PR% and HER2; moderate agreement for tumor type, grade, and ER%; and fair agreement for Ki67%. In 8% of patients (n = 13), tumor heterogeneity was seen. In heterogeneous tumors the overall concordance between the CNB and SS was worse, especially for HER2. Six of these patients had areas of tumor that were positive for HER2, which were not detected in their CNBs. Nine patients had multiple distinct molecular subtypes within their tumor(s). Conclusions: The heterogeneous distribution of antigens in breast cancer tumors raises concern that the CNB may not adequately represent the true biologic profile in all patients. There is strong concordance for tumor type, ER, and PR between CNB and SS (although a quantitative decline was noted from CNB to SS); however, HER2 activity does not appear to be adequately detected on CNB in patients with heterogeneous tumors. These data suggest that IHC testing on the CNB alone may not be adequate to tailor targeted therapy in all patients.

Original languageEnglish (US)
Pages (from-to)239-251
Number of pages13
JournalJournal of the American College of Surgeons
Volume216
Issue number2
DOIs
StatePublished - Feb 2013
Externally publishedYes

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Large-Core Needle Biopsy
Staining and Labeling
Breast Neoplasms
Epidermal Growth Factor
Neoplasms
Progesterone Receptors
Estrogen Receptors
Tumor Biomarkers
Prospective Studies

Keywords

  • AAMC
  • Anne Arundel Medical Center
  • CNB
  • core needle biopsy
  • ER
  • estrogen receptor
  • FISH
  • fluorescent in situ hybridization
  • H&E
  • hematoxylin and eosin
  • HER2
  • human epidermal growth factor 2
  • IHC
  • immunohistochemical
  • PR
  • progesterone receptor
  • Walter Reed National Military Medical Center
  • WRNMMC

ASJC Scopus subject areas

  • Surgery

Cite this

Does breast tumor heterogeneity necessitate further immunohistochemical staining on surgical specimens? / Greer, Lauren T.; Rosman, Martin; Mylander, W. Charles; Hooke, Jeffrey; Kovatich, Albert; Sawyer, Kristen; Buras, Robert R.; Shriver, Craig D.; Tafra, Lorraine.

In: Journal of the American College of Surgeons, Vol. 216, No. 2, 02.2013, p. 239-251.

Research output: Contribution to journalArticle

Greer, LT, Rosman, M, Mylander, WC, Hooke, J, Kovatich, A, Sawyer, K, Buras, RR, Shriver, CD & Tafra, L 2013, 'Does breast tumor heterogeneity necessitate further immunohistochemical staining on surgical specimens?', Journal of the American College of Surgeons, vol. 216, no. 2, pp. 239-251. https://doi.org/10.1016/j.jamcollsurg.2012.09.007
Greer, Lauren T. ; Rosman, Martin ; Mylander, W. Charles ; Hooke, Jeffrey ; Kovatich, Albert ; Sawyer, Kristen ; Buras, Robert R. ; Shriver, Craig D. ; Tafra, Lorraine. / Does breast tumor heterogeneity necessitate further immunohistochemical staining on surgical specimens?. In: Journal of the American College of Surgeons. 2013 ; Vol. 216, No. 2. pp. 239-251.
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abstract = "Background: Prognostic and predictive tumor markers in breast cancer are most commonly performed on core needle biopsies (CNB) of the primary tumor. Because treatment recommendations are influenced by these markers, it is imperative to verify strong concordance between tumor markers on CNB specimens and the corresponding surgical specimens (SS). Study Design: A prospective study was performed on 165 women (205 samples) with breast cancer diagnosed from January 2009 to July 2011. Tumor type, grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki67 expression by immunohistochemical (IHC) testing were retrospectively analyzed in the CNB and SS. Contingency tables and agreement modeling were performed. Results: There was substantial agreement between the CNB and SS for PR{\%} and HER2; moderate agreement for tumor type, grade, and ER{\%}; and fair agreement for Ki67{\%}. In 8{\%} of patients (n = 13), tumor heterogeneity was seen. In heterogeneous tumors the overall concordance between the CNB and SS was worse, especially for HER2. Six of these patients had areas of tumor that were positive for HER2, which were not detected in their CNBs. Nine patients had multiple distinct molecular subtypes within their tumor(s). Conclusions: The heterogeneous distribution of antigens in breast cancer tumors raises concern that the CNB may not adequately represent the true biologic profile in all patients. There is strong concordance for tumor type, ER, and PR between CNB and SS (although a quantitative decline was noted from CNB to SS); however, HER2 activity does not appear to be adequately detected on CNB in patients with heterogeneous tumors. These data suggest that IHC testing on the CNB alone may not be adequate to tailor targeted therapy in all patients.",
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AU - Greer, Lauren T.

AU - Rosman, Martin

AU - Mylander, W. Charles

AU - Hooke, Jeffrey

AU - Kovatich, Albert

AU - Sawyer, Kristen

AU - Buras, Robert R.

AU - Shriver, Craig D.

AU - Tafra, Lorraine

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N2 - Background: Prognostic and predictive tumor markers in breast cancer are most commonly performed on core needle biopsies (CNB) of the primary tumor. Because treatment recommendations are influenced by these markers, it is imperative to verify strong concordance between tumor markers on CNB specimens and the corresponding surgical specimens (SS). Study Design: A prospective study was performed on 165 women (205 samples) with breast cancer diagnosed from January 2009 to July 2011. Tumor type, grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki67 expression by immunohistochemical (IHC) testing were retrospectively analyzed in the CNB and SS. Contingency tables and agreement modeling were performed. Results: There was substantial agreement between the CNB and SS for PR% and HER2; moderate agreement for tumor type, grade, and ER%; and fair agreement for Ki67%. In 8% of patients (n = 13), tumor heterogeneity was seen. In heterogeneous tumors the overall concordance between the CNB and SS was worse, especially for HER2. Six of these patients had areas of tumor that were positive for HER2, which were not detected in their CNBs. Nine patients had multiple distinct molecular subtypes within their tumor(s). Conclusions: The heterogeneous distribution of antigens in breast cancer tumors raises concern that the CNB may not adequately represent the true biologic profile in all patients. There is strong concordance for tumor type, ER, and PR between CNB and SS (although a quantitative decline was noted from CNB to SS); however, HER2 activity does not appear to be adequately detected on CNB in patients with heterogeneous tumors. These data suggest that IHC testing on the CNB alone may not be adequate to tailor targeted therapy in all patients.

AB - Background: Prognostic and predictive tumor markers in breast cancer are most commonly performed on core needle biopsies (CNB) of the primary tumor. Because treatment recommendations are influenced by these markers, it is imperative to verify strong concordance between tumor markers on CNB specimens and the corresponding surgical specimens (SS). Study Design: A prospective study was performed on 165 women (205 samples) with breast cancer diagnosed from January 2009 to July 2011. Tumor type, grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki67 expression by immunohistochemical (IHC) testing were retrospectively analyzed in the CNB and SS. Contingency tables and agreement modeling were performed. Results: There was substantial agreement between the CNB and SS for PR% and HER2; moderate agreement for tumor type, grade, and ER%; and fair agreement for Ki67%. In 8% of patients (n = 13), tumor heterogeneity was seen. In heterogeneous tumors the overall concordance between the CNB and SS was worse, especially for HER2. Six of these patients had areas of tumor that were positive for HER2, which were not detected in their CNBs. Nine patients had multiple distinct molecular subtypes within their tumor(s). Conclusions: The heterogeneous distribution of antigens in breast cancer tumors raises concern that the CNB may not adequately represent the true biologic profile in all patients. There is strong concordance for tumor type, ER, and PR between CNB and SS (although a quantitative decline was noted from CNB to SS); however, HER2 activity does not appear to be adequately detected on CNB in patients with heterogeneous tumors. These data suggest that IHC testing on the CNB alone may not be adequate to tailor targeted therapy in all patients.

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KW - hematoxylin and eosin

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KW - PR

KW - progesterone receptor

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KW - WRNMMC

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