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

Narbe, Ulrik LU ; Sjöström, Martin LU ; Forsare, Carina LU ; Bendahl, Pär Ola LU ; Alkner, Sara LU ; Leeb-Lundberg, L. M.Fredrik LU ; Lövgren, Kristina LU ; Rydén, Lisa LU ; Ingvar, Christian LU and Fernö, Mårten LU (2019) In Breast Cancer Research and Treatment
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... (More)

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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organization
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type
Contribution to journal
publication status
epub
subject
keywords
Amplified in breast cancer 1 (AIB1), Androgen receptor (AR), G protein-coupled estrogen receptor (GPER), Gene expression, Invasive lobular carcinoma (ILC), Prognostic biomarkers
in
Breast Cancer Research and Treatment
publisher
Springer
external identifiers
  • scopus:85061977659
ISSN
0167-6806
DOI
10.1007/s10549-019-05138-7
language
English
LU publication?
yes
id
9ba961e8-d371-4a9c-93f9-0590a426763b
date added to LUP
2019-03-07 12:12:53
date last changed
2019-03-27 04:40:23
@article{9ba961e8-d371-4a9c-93f9-0590a426763b,
  abstract     = {<p>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 &gt; 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.</p>},
  author       = {Narbe, Ulrik and Sjöström, Martin and Forsare, Carina and Bendahl, Pär Ola and Alkner, Sara and Leeb-Lundberg, L. M.Fredrik and Lövgren, Kristina and Rydén, Lisa and Ingvar, Christian and Fernö, Mårten},
  issn         = {0167-6806},
  keyword      = {Amplified in breast cancer 1 (AIB1),Androgen receptor (AR),G protein-coupled estrogen receptor (GPER),Gene expression,Invasive lobular carcinoma (ILC),Prognostic biomarkers},
  language     = {eng},
  month        = {02},
  publisher    = {Springer},
  series       = {Breast Cancer Research and Treatment},
  title        = {The estrogen receptor coactivator AIB1 is a new putative prognostic biomarker in ER-positive/HER2-negative invasive lobular carcinoma of the breast},
  url          = {http://dx.doi.org/10.1007/s10549-019-05138-7},
  year         = {2019},
}