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BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

A prospective comparison of ER, PR, Ki67 and gene expression in paired sequential core biopsies of primary, untreated breast cancer

Authors: Sirwan M. Hadad, Lee B. Jordan, Pankaj G. Roy, Colin A. Purdie, Takayuki Iwamoto, Lajos Pusztai, Stacy L. Moulder-Thompson, Alastair M. Thompson

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

Sequential biopsy of breast cancer is used to assess biomarker effects and drug efficacy. The preoperative “window of opportunity” setting is advantageous to test biomarker changes in response to therapeutic agents in previously untreated primary cancers. This study tested the consistency over time of paired, sequential biomarker measurements on primary, operable breast cancer in the absence of drug therapy.

Methods

Immunohistochemistry was performed for ER, PR and Ki67 on paired preoperative/operative tumor samples taken from untreated patients within 2 weeks of each other. Microarray analysis on mRNA extracted from formalin fixed paraffin embedded cores was performed using Affymetrix based arrays on paired core biopsies analysed using Ingenuity Pathway Analysis (IPA) and Gene Set Analysis (GSA).

Results

In 41 core/resection pairs, the recognised trend to lower ER, PR and Ki67 score on resected material was confirmed. Concordance for ER, PR and Ki67 without changing biomarker status (e.g. ER+ to ER-) was 90, 74 and 80 % respectively. However, in 23 paired core samples (diagnostic core v on table core), Ki67 using a cut off of 13.25 % was concordant in 22/23 (96 %) and differences in ER and PR immunohistochemistry by Allred or Quickscore between the pairs did not impact hormone receptor status. IPA and GSA demonstrated substantial gene expression changes between paired cores at the mRNA level, including reduced expression of ER pathway analysis on the second core, despite the absence of drug intervention.

Conclusions

Sequential core biopsies of primary breast cancer (but not core versus resection) was consistent and is appropriate to assess the effects of drug therapy in vivo on ER, PR and Ki67 using immunohistochemistry. Conversely, studies utilising mRNA expression may require non-treatment controls to distinguish therapeutic from biopsy differences.
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Metadata
Title
A prospective comparison of ER, PR, Ki67 and gene expression in paired sequential core biopsies of primary, untreated breast cancer
Authors
Sirwan M. Hadad
Lee B. Jordan
Pankaj G. Roy
Colin A. Purdie
Takayuki Iwamoto
Lajos Pusztai
Stacy L. Moulder-Thompson
Alastair M. Thompson
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2788-x

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