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

J Am Coll Surg. 2013 Feb;216(2):239-51. doi: 10.1016/j.jamcollsurg.2012.09.007. Epub 2012 Nov 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biomarkers, Tumor / analysis
  • Biopsy, Needle
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery*
  • Female
  • Humans
  • Immunohistochemistry*
  • Neoplasm Grading
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Retrospective Studies
  • Sensitivity and Specificity


  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone