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Open Access 01-06-2019 | Breast Cancer | Preclinical study

The estrogen receptor coactivator AIB1 is a new putative prognostic biomarker in ER-positive/HER2-negative invasive lobular carcinoma of the breast

Authors: Ulrik Narbe, Martin Sjöström, Carina Forsare, Pär-Ola Bendahl, Sara Alkner, L. M. Fredrik Leeb-Lundberg, Kristina Lövgren, Lisa Rydén, Christian Ingvar, Mårten Fernö

Published in: Breast Cancer Research and Treatment | Issue 2/2019

Abstract

Purpose

According to the 2017 St Gallen surrogate definitions of the intrinsic subtypes, Ki67, progesterone receptor (PR) and Nottingham histological grade (NHG) are used for prognostic classification of estrogen receptor (ER) positive/HER2-negative breast cancer into luminal A- or luminal B-like. The aim of the present study was to investigate if additional biomarkers, related to endocrine signaling pathways, e.g., amplified in breast cancer 1 (AIB1), androgen receptor (AR), and G protein-coupled estrogen receptor (GPER), can provide complementary prognostic information in a subset of ER-positive/HER-negative invasive lobular carcinoma (ILC).

Methods

Biomarkers from 224 patients were analyzed immunohistochemically on tissue microarray. The primary endpoint was breast cancer mortality (BCM), analyzed with 10- and 25-year follow-up (FU). In addition, the prognostic value of gene expression data for these biomarkers was analyzed in three publicly available ILC datasets.

Results

AIB1 (high vs. low) was associated to BCM in multivariable analysis (adjusted for age, tumor size, nodal status, NHG, Ki67, luminal-like classification, and adjuvant systemic therapy) with 10-year FU (HR 6.8, 95% CI 2.3–20, P = 0.001) and 25-year FU (HR 3.0, 95% CI 1.1–7.8, P = 0.03). The evidence of a prognostic effect of AIB1 could be confirmed by linking gene expression data to outcome in independent publicly available ILC datasets. AR and GPER were neither associated to BCM with 10-year nor with 25-year FU (P > 0.33). Furthermore, Ki67 and NHG were prognostic for BCM at both 10-year and 25-year FU, whereas PR was not.

Conclusions

AIB1 is a new putative prognostic biomarker in ER-positive/HER2-negative ILC.

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When averaging over two scores differing by one unit, the result will be non-integer.

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Title: The estrogen receptor coactivator AIB1 is a new putative prognostic biomarker in ER-positive/HER2-negative invasive lobular carcinoma of the breast
Authors: Ulrik Narbe
Martin Sjöström
Carina Forsare
Pär-Ola Bendahl
Sara Alkner
L. M. Fredrik Leeb-Lundberg
Kristina Lövgren
Lisa Rydén
Christian Ingvar
Mårten Fernö
Publication date: 01-06-2019
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Biomarkers
Estrogens
Androgens
Published in: Breast Cancer Research and Treatment / Issue 2/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05138-7

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