Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jun;175(2):305-316.
doi: 10.1007/s10549-019-05138-7. Epub 2019 Feb 22.

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

Ulrik Narbe  1   2 , Martin Sjöström  3 , Carina Forsare  3 , Pär-Ola Bendahl  3 , Sara Alkner  3   4 , L M Fredrik Leeb-Lundberg  5 , Kristina Lövgren  3 , Lisa Rydén  6   7 , Christian Ingvar  6   7 , Mårten Fernö  3
Affiliations

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

Ulrik Narbe et al. Breast Cancer Res Treat. 2019 Jun.

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.

Keywords: Amplified in breast cancer 1 (AIB1); Androgen receptor (AR); G protein-coupled estrogen receptor (GPER); Gene expression; Invasive lobular carcinoma (ILC); Prognostic biomarkers.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Consort diagram: Breast cancer patients with tumors primarily classified as invasive lobular carcinomas (ILC) at the Department of Pathology, Skåne University Hospital Lund and Helsingborg Hospital, (1980–1991), N = 319. ER positivity (≥ 1%) was confirmed with IHC staining on tissue microarray in N = 200 and whole tissue sections in N = 21, and with cytosol-based methods in N = 3 tumor samples
Fig. 2
Fig. 2
Representative images of immunohistochemical staining of AIB1, AR, and GPER: a AIB1 low (score 0) b AIB1: high (score 6) c AR negative (≤ 10%) d AR positive (> 10%). e Total GPER negative (level 0) f Total GPER very weak (level 1) g Total GPER weak (level 2) h Total GPER moderate (level 3). None of the TMAs were classified as total GPER strong (level 4)
Fig. 3
Fig. 3
AIB1: Breast cancer mortality (10- and 25-year FU)
Fig. 4
Fig. 4
AIB1: Risk of breast cancer death assessed by gene expression data in three independent publicly available datasets of invasive lobular carcinoma (P value: log-rank test)
See this image and copyright information in PMC

References

    1. Garcia-Fernandez A, Lain JM, Chabrera C, Garcia Font M, Fraile M, Barco I, Torras M, Rene A, Gonzalez S, Gonzalez C, Piqueras M, Veloso E, Cirera L, Pessarrodona A, Gimenez N. Comparative Long-term Study of a Large Series of Patients with Invasive Ductal Carcinoma and Invasive Lobular Carcinoma. Loco-Regional Recurrence, Metastasis, and Survival. Breast J. 2015;21(5):533–537. doi: 10.1111/tbj.12455. - DOI - PubMed
    1. Rakha EA, Gill MS, El-Sayed ME, Khan MM, Hodi Z, Blamey RW, Evans AJ, Lee AH, Ellis IO. The biological and clinical characteristics of breast carcinoma with mixed ductal and lobular morphology. Breast Cancer Res Treat. 2009;114(2):243–250. doi: 10.1007/s10549-008-0007-4. - DOI - PubMed
    1. Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ (eds) (2012) WHO Classification of Tumours of the Breast. 4th Edn. WHO press
    1. Martinez V, Azzopardi JG. Invasive lobular carcinoma of the breast: incidence and variants. Histopathology. 1979;3(6):467–488. doi: 10.1111/j.1365-2559.1979.tb03029.x. - DOI - PubMed
    1. Acs G, Lawton TJ, Rebbeck TR, LiVolsi VA, Zhang PJ. Differential expression of E-cadherin in lobular and ductal neoplasms of the breast and its biologic and diagnostic implications. Am J Clin Pathol. 2001;115(1):85–98. doi: 10.1309/FDHX-L92R-BATQ-2GE0. - DOI - PubMed

MeSH terms