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
(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
- Alkner, S. LU ; Jensen, Brian M. ; Rasmussen, Birgitte B. ; Bendahl, P. O. LU ; Fernö, M. LU ; Rydén, L. LU and Mouridsen, H.
- organization
- publishing date
- 2017-08-01
- 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
-
- scopus:85026549097
- pmid:28766132
- wos:000414472400014
- 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
- 2024-06-09 21:52:06
@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}}, }