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Annals of Oncology Advance Access first published online on October 25, 2009
This version published online on November 3, 2009

Annals of Oncology, doi:10.1093/annonc/mdp427
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Quantitative analysis of changes in ER, PR and HER2 expression in primary breast cancer and paired nodal metastases

S.J. Aitken, J.S. Thomas, S.P. Langdon, D.J. Harrison and D. Faratian*

Edinburgh Breakthrough Research Unit and Division of Pathology, University of Edinburgh, Edinburgh, UK

* Correspondence to: Dr D. Faratian, Edinburgh Breakthrough Research Unit and Division of Pathology, Crewe Road South, Edinburgh EH4 2XU, UK. Tel: +44-131-537-1763; Fax: +44-131-537-3159; E-mail: d.faratian{at}ed.ac.uk

Background: Assessment of receptors [estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)] is routinely carried out on primary tumour in order to select appropriate adjuvant therapy; the same analysis is not carried out on nodal metastases. Since de novo resistance to therapy is common, we quantified differences in receptor expression between primary and nodal disease in order to assess whether this might contribute to therapeutic resistance.

Patients and methods: A total of 385 patients with invasive primary breast carcinomas and paired lymph nodes (n = 211) were assessed for ER, PR and HER2 expression using quantitative immunofluorescence. Cut-points were defined by comparison with tumours scored by immunohistochemistry (IHC) and FISH. Differences in expression for each of the markers and molecular phenotype were analysed.

Results: Quantitative receptor expression shows a wide dynamic range compared with IHC. Overall, 46.9% cases had disparate breast/node receptor status of at least one receptor. Many of the differences in expression between primary tumour and node are large magnitude (greater than fivefold) changes. Triple-negative phenotype changes in 23.1% of cases.

Conclusions: A significant number of patients show discordant quantitative expression of molecular markers between primary and nodal disease. Appropriately measured, lymph node receptor status could be a more accurate measurement for guiding adjuvant therapy, which requires testing in a clinical trial.

breast cancer, ER, HER2, image analysis, molecular phenotype, nodal metastases, PR

Received for publication June 6, 2009. Revision received July 29, 2009. Accepted for publication July 30, 2009.


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