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Prognostic and predictive importance of the estrogen receptor coactivator AIB1 in a randomized trial comparing adjuvant letrozole and tamoxifen therapy in postmenopausal breast cancer : the Danish cohort of BIG 1-98

Alkner, S. LU ; Jensen, Brian M. ; Rasmussen, Birgitte B. ; Bendahl, P. O. LU ; Fernö, M. LU ; Rydén, L. LU orcid and Mouridsen, H. (2017) In Breast Cancer Research and Treatment 166. p.481-490
Abstract

Purpose: To evaluate the estrogen receptor coactivator amplified in breast cancer 1 (AIB1) as a prognostic marker, as well as a predictive marker for response to adjuvant tamoxifen and/or aromatase inhibitors, in early estrogen receptor-positive breast cancer. Method: AIB1 was analyzed with immunohistochemistry in tissue microarrays of the Danish subcohort (N = 1396) of the International Breast Cancer Study Group’s trial BIG 1-98 (randomization between adjuvant tamoxifen versus letrozole versus the sequence of the two drugs). Results: Forty-six percent of the tumors had a high AIB1 expression. In line with previous studies, AIB1 correlated to a more aggressive tumor-phenotype (HER2 amplification and a high malignancy grade). High AIB1... (More)

Purpose: To evaluate the estrogen receptor coactivator amplified in breast cancer 1 (AIB1) as a prognostic marker, as well as a predictive marker for response to adjuvant tamoxifen and/or aromatase inhibitors, in early estrogen receptor-positive breast cancer. Method: AIB1 was analyzed with immunohistochemistry in tissue microarrays of the Danish subcohort (N = 1396) of the International Breast Cancer Study Group’s trial BIG 1-98 (randomization between adjuvant tamoxifen versus letrozole versus the sequence of the two drugs). Results: Forty-six percent of the tumors had a high AIB1 expression. In line with previous studies, AIB1 correlated to a more aggressive tumor-phenotype (HER2 amplification and a high malignancy grade). High AIB1 also correlated to higher estrogen receptor expression (80–100 vs. 1–79%), and ductal histological type. High AIB1 expression was associated with a poor disease-free survival (univariable: hazard ratio 1.35, 95% confidence interval 1.12–1.63. Multivariable: hazard ratio 1.29, 95% confidence interval 1.06–1.58) and overall survival (univariable: hazard ratio 1.34, 95% confidence interval 1.07–1.68. Multivariable: hazard ratio 1.25, 95% confidence interval 0.99–1.60). HER2 did not seem to modify the prognostic effect of AIB1. No difference in treatment effect between tamoxifen and letrozole in relation to AIB1 was found. Conclusions: In a subset of the large international randomized trial BIG 1-98, we confirm AIB1 to be a strong prognostic factor in early breast cancer. Hence, although tumor AIB1 expression does not seem to be useful for the choice of tamoxifen versus an aromatase inhibitor in postmenopausal endocrine-responsive breast cancer, AIB1 is an interesting target for new anti-cancer therapies and further investigations of this biomarker is warranted.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Amplified in breast cancer 1 (AIB1), Aromatase inhibitor, BIG 1-98, Breast cancer, Randomized trial, Tamoxifen
in
Breast Cancer Research and Treatment
volume
166
pages
481 - 490
publisher
Springer
external identifiers
  • pmid:28766132
  • wos:000414472400014
  • scopus:85026549097
ISSN
0167-6806
DOI
10.1007/s10549-017-4416-0
language
English
LU publication?
yes
id
ecdb404e-dcd4-4e8d-9a4b-a59a1549a9f3
date added to LUP
2017-08-21 15:04:53
date last changed
2022-05-02 21:48:32
@article{ecdb404e-dcd4-4e8d-9a4b-a59a1549a9f3,
  abstract     = {{<p>Purpose: To evaluate the estrogen receptor coactivator amplified in breast cancer 1 (AIB1) as a prognostic marker, as well as a predictive marker for response to adjuvant tamoxifen and/or aromatase inhibitors, in early estrogen receptor-positive breast cancer. Method: AIB1 was analyzed with immunohistochemistry in tissue microarrays of the Danish subcohort (N = 1396) of the International Breast Cancer Study Group’s trial BIG 1-98 (randomization between adjuvant tamoxifen versus letrozole versus the sequence of the two drugs). Results: Forty-six percent of the tumors had a high AIB1 expression. In line with previous studies, AIB1 correlated to a more aggressive tumor-phenotype (HER2 amplification and a high malignancy grade). High AIB1 also correlated to higher estrogen receptor expression (80–100 vs. 1–79%), and ductal histological type. High AIB1 expression was associated with a poor disease-free survival (univariable: hazard ratio 1.35, 95% confidence interval 1.12–1.63. Multivariable: hazard ratio 1.29, 95% confidence interval 1.06–1.58) and overall survival (univariable: hazard ratio 1.34, 95% confidence interval 1.07–1.68. Multivariable: hazard ratio 1.25, 95% confidence interval 0.99–1.60). HER2 did not seem to modify the prognostic effect of AIB1. No difference in treatment effect between tamoxifen and letrozole in relation to AIB1 was found. Conclusions: In a subset of the large international randomized trial BIG 1-98, we confirm AIB1 to be a strong prognostic factor in early breast cancer. Hence, although tumor AIB1 expression does not seem to be useful for the choice of tamoxifen versus an aromatase inhibitor in postmenopausal endocrine-responsive breast cancer, AIB1 is an interesting target for new anti-cancer therapies and further investigations of this biomarker is warranted.</p>}},
  author       = {{Alkner, S. and Jensen, Brian M. and Rasmussen, Birgitte B. and Bendahl, P. O. and Fernö, M. and Rydén, L. and Mouridsen, H.}},
  issn         = {{0167-6806}},
  keywords     = {{Amplified in breast cancer 1 (AIB1); Aromatase inhibitor; BIG 1-98; Breast cancer; Randomized trial; Tamoxifen}},
  language     = {{eng}},
  month        = {{08}},
  pages        = {{481--490}},
  publisher    = {{Springer}},
  series       = {{Breast Cancer Research and Treatment}},
  title        = {{Prognostic and predictive importance of the estrogen receptor coactivator AIB1 in a randomized trial comparing adjuvant letrozole and tamoxifen therapy in postmenopausal breast cancer : the Danish cohort of BIG 1-98}},
  url          = {{http://dx.doi.org/10.1007/s10549-017-4416-0}},
  doi          = {{10.1007/s10549-017-4416-0}},
  volume       = {{166}},
  year         = {{2017}},
}