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Breast Cancer Research
Published in: Breast Cancer Research 4/2013

Open Access 01-08-2013 | Research article

Estrogen receptor negative/progesterone receptor positive breast cancer is not a reproducible subtype

Authors: Marco M Hefti, Rong Hu, Nicholas W Knoblauch, Laura C Collins, Benjamin Haibe-Kains, Rulla M Tamimi, Andrew H Beck

Published in: Breast Cancer Research | Issue 4/2013

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Abstract

Introduction

Estrogen receptor (ER) and progesterone receptor (PR) testing are performed in the evaluation of breast cancer. While the clinical utility of ER as a predictive biomarker to identify patients likely to benefit from hormonal therapy is well-established, the added value of PR is less well-defined. The primary goals of our study were to assess the distribution, inter-assay reproducibility, and prognostic significance of breast cancer subtypes defined by patterns of ER and PR expression.

Methods

We integrated gene expression microarray (GEM) and clinico-pathologic data from 20 published studies to determine the frequency (n = 4,111) and inter-assay reproducibility (n = 1,752) of ER/PR subtypes (ER+/PR+, ER+/PR-, ER-/PR-, ER-/PR+). To extend our findings, we utilized a cohort of patients from the Nurses’ Health Study (NHS) with ER/PR data recorded in the medical record and assessed on tissue microarrays (n = 2,011). In both datasets, we assessed the association of ER and PR expression with survival.

Results

In a genome-wide analysis, progesterone receptor was among the least variable genes in ER- breast cancer. The ER-/PR+ subtype was rare (approximately 1 to 4%) and showed no significant reproducibility (Kappa = 0.02 and 0.06, in the GEM and NHS datasets, respectively). The vast majority of patients classified as ER-/PR+ in the medical record (97% and 94%, in the GEM and NHS datasets) were re-classified by a second method. In the GEM dataset (n = 2,731), progesterone receptor mRNA expression was associated with prognosis in ER+ breast cancer (adjusted P <0.001), but not in ER- breast cancer (adjusted P = 0.21). PR protein expression did not contribute significant prognostic information to multivariate models considering ER and other standard clinico-pathologic features in the GEM or NHS datasets.

Conclusion

ER-/PR+ breast cancer is not a reproducible subtype. PR expression is not associated with prognosis in ER- breast cancer, and PR does not contribute significant independent prognostic information to multivariate models considering ER and other standard clinico-pathologic factors. Given that PR provides no clinically actionable information in ER+ breast cancer, these findings question the utility of routine PR testing in breast cancer.
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Metadata
Title
Estrogen receptor negative/progesterone receptor positive breast cancer is not a reproducible subtype
Authors
Marco M Hefti
Rong Hu
Nicholas W Knoblauch
Laura C Collins
Benjamin Haibe-Kains
Rulla M Tamimi
Andrew H Beck
Publication date
01-08-2013
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 4/2013
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3462

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