Prior Adjuvant Tamoxifen Treatment in Breast Cancer Is Linked to Increased AIB1 and HER2 Expression in Metachronous Contralateral Breast Cancer

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Mar 10

PMID 26959415

Citations 6

Authors

Sara Alkner

Par-Ola Bendahl

Anna Ehinger

Kristina Lovgren

Lisa Ryden

Marten Ferno

Affiliations

Soon will be listed here.

Abstract

Aim: The estrogen receptor coactivator Amplified in Breast Cancer 1 (AIB1) has been associated with an improved response to adjuvant tamoxifen in breast cancer, but also with endocrine treatment resistance. We hereby use metachronous contralateral breast cancer (CBC) developed despite prior adjuvant tamoxifen for the first tumor as an "in vivo"-model for tamoxifen resistance. AIB1-expression in the presumable resistant (CBC after prior tamoxifen) and naïve setting (CBC without prior tamoxifen) is compared and correlated to prognosis after CBC.

Methods: From a well-defined population-based cohort of CBC-patients we have constructed a unique tissue-microarray including >700 patients.

Results: CBC developed after adjuvant tamoxifen more often had a HER2-positive/triple negative-subtype and a high AIB1-expression (37% vs. 23%, p = 0.009), than if no prior endocrine treatment had been administered. In patients with an estrogen receptor (ER) positive CBC, a high AIB1-expression correlated to an inferior prognosis. However, these patients seemed to respond to tamoxifen, but only if endocrine therapy had not been administered for BC1.

Conclusions: Metachronous CBC developed after prior endocrine treatment has a decreased ER-expression and an increased HER2-expression. This is consistent with endocrine treatment escape mechanisms previously suggested, and indicates metachronous CBC to be a putative model for studies of treatment resistance "in vivo". The increased AIB1-expression in CBC developed after prior tamoxifen suggests a role of AIB1 in endocrine treatment resistance. In addition, we found indications that the response to tamoxifen in CBC with a high AIB1-expression seem to differ depending on previous exposure to this drug. A different function for AIB1 in the tamoxifen treatment naïve vs. resistant setting is suggested, and may explain previously conflicting results where a high AIB1-expression has been correlated to both a good response to adjuvant tamoxifen and tamoxifen resistance.

Citing Articles

AIB1/SRC-3/NCOA3 function in estrogen receptor alpha positive breast cancer.

Kiliti A, Sharif G, Martin M, Wellstein A, Riegel A Front Endocrinol (Lausanne). 2023; 14:1250218.

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Plasma membrane expression of G protein-coupled estrogen receptor (GPER)/G protein-coupled receptor 30 (GPR30) is associated with worse outcome in metachronous contralateral breast cancer.

Tutzauer J, Sjostrom M, Bendahl P, Ryden L, Ferno M, Leeb-Lundberg L PLoS One. 2020; 15(4):e0231786.

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Expression of HIF-1α is related to a poor prognosis and tamoxifen resistance in contralateral breast cancer.

Jogi A, Ehinger A, Hartman L, Alkner S PLoS One. 2019; 14(12):e0226150.

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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 U, Sjostrom M, Forsare C, Bendahl P, Alkner S, Leeb-Lundberg L Breast Cancer Res Treat. 2019; 175(2):305-316.

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A unifying biology of sex steroid-induced apoptosis in prostate and breast cancers.

Maximov P, Abderrahman B, Curpan R, Hawsawi Y, Fan P, Jordan V Endocr Relat Cancer. 2017; 25(2):R83-R113.

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