Abstract P1-01-15: Breast cancer biomarkers: Global tumor biomarker quality assurance study of intratumor heterogeneity
Authors: Dabbs DJ , Clark B 
Published: May 2016

Introduction

Biomarkers (BM) are often performed on core biopsies(CB) of breast tumors for treatment purposes, yet comprehensive information on BM heterogeneity is lacking. This quality assurance study is to survey BM intra-tumor heterogeneity (ITH) by comparing BM from CB and the examination of entire breast tumors from surgical excisions (SE). This interim report supplies data on 45/100 collected cases to date.

Methods:

Whole tumor cases, 3.0cm or less were collected in years 2013-2014, excluding neoadjuvant cases and were examined with CB by two pathologists. All tissues were processed using 2013 ASCO/CAP guidelines. Immunohistochemistry (IHC) for ER/PR/Her2/Ki67 was performed on breast core biopsies and each block of a tumor surgical excision (1-13 blocks per case). IHC was performed using the Ultra Ventana-Roche device with FDA IVD clones ER (SP1), PR(1E2) Her2(4B5) Ki67(30-9). Whole slides were semi-quantitated for ER/PR using HScore (0-300), Her2 was interpreted with 2013 ASCO/CAP guidelines and Ki67 proliferation index (PI) as estimated whole slide percent of tumor cell nuclear stain. Mean HScores and PI were calculated for all BM on SE, and CB deviations from the SE mean were calculated for ER/PR/Ki67. ITH of BM was assessed by comparing results among all tissue blocks for each case. Her2 results were descriptive. Eight cases lacked CB Ki67 PI.

Results

There were no cases in which categorical hormone receptors results (positive/negative) differed between CB and SE.

2/45 (4%) cases were Her2 positive, and 13/45(28%) were equivocal by IHC with one case amplified by in situ hybridization.

Comparing ER between CB/SE , 3/45 differed in HScores by 30% or more. 10/45 SE ER had ITH of 25% or more among different tissue blocks. 14/45 cases had CB/SE PR difference in HScore of 30% or more. 18/45 cases had SE PR with ITH HScore of 25% or more between tissue blocks.

Ki67 PI differed between CB/SE by more than 25% in 18/37 cases, with ITH among tissue blocks of more than 25% in 23/37 cases. The variability of CB-SE results and ITH among tissue blocks are summarized in table 1.

Table 1 Summary of ResultsCB-SE ERITH ERCB-SE PRITH PRCB- SE PIITH PI&gt;30%&gt;25%&gt;30%&gt;25%&gt;25%&gt;25%3/4510/45 (22%)14/45 (31%)18/45 (40%)18/37(49%)23/37(62%)CB-SE: core biopsy vs surgical excision; ER PR as H Score

Conclusions

In this interim report of 45/100 cases, (1) ITH of 25% or more occurred for ER content in 22 % of cases (2) similar ITH exists for PR content in 40% of cases. (3) Ki67 PI tissue block ITH was expressed with variation of 25% or more in 23/37 cases.

(4) While this degree of variability of BM may not affect treatment decisions, the tissues show sufficient BM variability that should stimulate concern for accuracy of results of prognostic gene expression profiles and genomic testing of breast tumors.

Citation Format: Dabbs DJ, Clark B. Breast cancer biomarkers: Global tumor biomarker quality assurance study of intratumor heterogeneity. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-01-15.