AGR2 Predicts Tamoxifen Resistance in Postmenopausal Breast Cancer Patients

Abstract

Endocrine resistance is a significant problem in breast cancer treatment. Thus identification and validation of novel resistance determinants is important to improve treatment efficacy and patient outcome. In our work, AGR2 expression was determined by qRT-PCR in Tru-Cut needle biopsies from tamoxifen-treated postmenopausal breast cancer patients. Our results showed inversed association of AGR2 mRNA levels with primary treatment response (P = 0.0011) and progression-free survival (P = 0.0366) in 61 ER-positive breast carcinomas. As shown by our experimental and clinical evaluations, elevated AGR2 expression predicts decreased efficacy of tamoxifen treatment. From this perspective, AGR2 is a potential predictive biomarker enabling selection of an optimal algorithm for adjuvant hormonal therapy in postmenopausal ER-positive breast cancer patients.

Anterior Gradient 2 is a Poor Outcome Indicator in Luminal Breast Cancer

“…[13][14][15] Interestingly, a worse DFS was also apparent in AGR2-positive luminal cancers with LN metastases but not in LN-negative cases. When adjusted for treatment and other prognostic factors, AGR2 was an independent prognostic factor, together with pT, pN, and HER2 status for DFS in node-positive luminal cancers.…”

“…11 Clinically, high AGR2 expression is associated with poor outcome in ER-positive cancers and hormonally treated breast cancers. 8,[12][13][14][15] It also correlates with lower Electronic supplementary material The online version of this article (…”

“…11 Clinically, high AGR2 expression is associated with poor outcome in ER-positive cancers and hormonally treated breast cancers. 8,[12][13][14][15] It also correlates with lower tumor grade, epidermal growth factor receptor (EGFR) negativity, and ER positivity. 2,15 Apart from these, relatively little is known about AGR2 in breast cancers, its relationship with clinicopathologic parameters, or its metastatic status.…”

Mechanisms of anterior gradient-2 regulation and function in cancer

“…In addition to the induction of agr2 expression by oestrogen or oestrogen-mimetics like tamoxifen, in post-menopausal women, agr2 expression also predicts poor responses [66], possibly through an AKT signalling pathway [67] or an EGFR-dependent pathway [68]. Although agr2 and/or agr3 expression are reported to be linked to oestrogens or androgens in some cancers, there are clearly hormone-independent pathways that trigger their induction in liver, colorectal, lung, and pancreas to name a few [17,69,70].…”

AGR2 oncoprotein inhibits p38 MAPK and p53 activation through a DUSP10‐mediated regulatory pathway

“…Later, it was shown that AGR2 expression is directly stimulated by ER signaling (Salmans et al., 2013) and correlates with poor outcome of patients with ER‐positive breast cancer (Hrstka et al., 2010; Innes et al., 2006), which emphasizes the importance of estrogen receptors in the regulation of AGR2 expression. From a functional perspective, AGR2 was shown to promote tumor metastasis, cell survival, cell proliferation and resistance to therapy (Hrstka et al., 2013; Ramachandran et al., 2008; Wang et al., 2008). In addition to breast cancer, AGR2 was also detected in many other adenocarcinomas (Brychtova et al., 2011).…”