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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.

ABSTRACT: 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.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).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.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.

SUBMITTER: Alkner S

PROVIDER: S-EPMC5668343 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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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 S Jensen M-B MB Rasmussen B B BB Bendahl P-O PO Fernö M M Rydén L L Mouridsen H H

Breast cancer research and treatment 20170801 2

<h4>Purpose</h4>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.<h4>Method</h4>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 letr ...[more]

PMID: 28766132

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Project description:PurposeLuminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years.Patients and methodsBIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported.ResultsOf 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9% relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly over time (0- to 5-, 5- to 10-, and > 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P = .005), perhaps reflecting a longer carryover effect of tamoxifen. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up.ConclusionEfficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.

Dataset Information

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.

Publications

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.

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