Elodie Chantalat

Bio: Elodie Chantalat is an academic researcher from University of Toulouse. The author has contributed to research in topics: Medicine & Cervical cancer. The author has an hindex of 9, co-authored 61 publications receiving 275 citations.

Estrogen Receptors and Endometriosis.

Abstract: Endometriosis is a frequent and chronic inflammatory disease with impacts on reproduction, health and quality of life. This disorder is highly estrogen-dependent and the purpose of hormonal treatments is to decrease the endogenous ovarian production of estrogens. High estrogen production is a consistently observed endocrine feature of endometriosis. mRNA and protein levels of estrogen receptors (ER) are different between a normal healthy endometrium and ectopic/eutopic endometrial lesions: endometriotic stromal cells express extraordinarily higher ERβ and significantly lower ERα levels compared with endometrial stromal cells. Aberrant epigenetic regulation such as DNA methylation in endometriotic cells is associated with the pathogenesis and development of endometriosis. Although there is a large body of data regarding ERs in endometriosis, our understanding of the roles of ERα and ERβ in the pathogenesis of endometriosis remains incomplete. The goal of this review is to provide an overview of the links between endometriosis, ERs and the recent advances of treatment strategies based on ERs modulation. We will also attempt to summarize the current understanding of the molecular and cellular mechanisms of action of ERs and how this could pave the way to new therapeutic strategies.

The AF-1-deficient estrogen receptor ERα46 isoform is frequently expressed in human breast tumors

Abstract: To date, all studies conducted on breast cancer diagnosis have focused on the expression of the full-length 66-kDa estrogen receptor alpha (ERα66). However, much less attention has been paid to a shorter 46-kDa isoform (ERα46), devoid of the N-terminal region containing the transactivation function AF-1. Here, we investigated the expression levels of ERα46 in breast tumors in relation to tumor grade and size, and examined the mechanism of its generation and its specificities of coregulatory binding and its functional activities. Using approaches combining immunohistochemistry, Western blotting, and proteomics, antibodies allowing ERα46 detection were identified and the expression levels of ERα46 were quantified in 116 ERα-positive human breast tumors. ERα46 expression upon cellular stress was studied, and coregulator bindings, transcriptional, and proliferative response were determined to both ERα isoforms. ERα46 was expressed in over 70% of breast tumors at variable levels which sometimes were more abundant than ERα66, especially in differentiated, lower-grade, and smaller-sized tumors. We also found that ERα46 can be generated via internal ribosome entry site-mediated translation in the context of endoplasmic reticulum stress. The binding affinities of both unliganded and fully-activated receptors towards co-regulator peptides revealed that the respective potencies of ERα46 and ERα66 differ significantly, contributing to the differential transcriptional activity of target genes to 17β estradiol (E2). Finally, increasing amounts of ERα46 decrease the proliferation rate of MCF7 tumor cells in response to E2. We found that, besides the full-length ERα66, the overlooked ERα46 isoform is also expressed in a majority of breast tumors. This finding highlights the importance of the choice of antibodies used for the diagnosis of breast cancer, which are able or not to detect the ERα46 isoform. In addition, since the function of both ERα isoforms differs, this work underlines the need to develop new technologies in order to discriminate ERα66 and ERα46 expression in breast cancer diagnosis which could have potential clinical relevance.

Breast desmoid tumor management in France: toward a new strategy

Abstract: Desmoid tumors (DTs) are rare tumors that originate from myofibroblastic tissue. Recently, initial wait and see was recommended (ESMO guidelines Ann Oncol 2017) in the most frequent locations. This study investigates the outcome of breast desmoid tumor (BDT) according to the initial strategy. Data from all consecutive patients treated from a BDT in four referral centers were collected. Only intra-mammary desmoid tumors were included. A pathological review and a molecular analysis (CTNNB1 gene mutation) were performed (National re-reading network of sarcomas-RRePS). Patients were grouped according to initial strategy: surgery group (SG) and active surveillance group (ASG). A total of 63 patients (61 women, 2 men) met the inclusion criteria. Median age was 50 years (16–86). CTNNB1 mutation was found in 61% (n = 36). SG included 46 patients (73%) (41 partial mastectomies, 2 mastectomies, and 3 mastectomies associated to parietectomies). Surgical margins were positive in 15 patients (33.3%). Median follow-up of SG was 24.9 (0.5–209) months; and 4 patients (8.7%) developed recurrence. ASG included 17 patients (27%). Their median follow-up was 42.2 (0–214) months, and 15 patients (88.2%) did not require any additional treatment. Six patients (35%) had a spontaneous regression, 9 patients (52%) were stable, and 2 patients presented a significant progression that was treated by partial mastectomy. This study supports an initial nonsurgical approach to BDTs followed by surgery based on tumor growth in select cases, which is consistent with current ESMO recommendations.

Body Mass Index as a Major Risk Factor for Severe Breast Cancer-Related Lymphedema

Abstract: Background: A few studies have examined the characteristics of severe breast cancer-related lymphedema (BCRL). This study aims at analyzing the factors associated with severe lymphedema (LE) across...

Membrane and Nuclear Estrogen Receptor Alpha Actions: From Tissue Specificity to Medical Implications

Abstract: Estrogen receptor alpha (ERα) has been recognized now for several decades as playing a key role in reproduction and exerting functions in numerous nonreproductive tissues. In this review, we attempt to summarize the in vitro studies that are the basis of our current understanding of the mechanisms of action of ERα as a nuclear receptor and the key roles played by its two activation functions (AFs) in its transcriptional activities. We then depict the consequences of the selective inactivation of these AFs in mouse models, focusing on the prominent roles played by ERα in the reproductive tract and in the vascular system. Evidence has accumulated over the two last decades that ERα is also associated with the plasma membrane and activates non-nuclear signaling from this site. These rapid/nongenomic/membrane-initiated steroid signals (MISS) have been characterized in a variety of cell lines, and in particular in endothelial cells. The development of selective pharmacological tools that specifically activate MISS and the generation of mice expressing an ERα protein impeded for membrane localization have begun to unravel the physiological role of MISS in vivo. Finally, we discuss novel perspectives for the design of tissue-selective ER modulators based on the integration of the physiological and pathophysiological roles of MISS actions of estrogens.

Iconographies supplémentaires de l'article : Feasibility and clinical outcome of laparoscopic colorectal resection for endometriosis

Abstract: OBJECTIVE This study was undertaken to evaluate the feasibility and complications of laparoscopic segmental colorectal resection for endometriosis and its efficacy on gynecologic and digestive symptoms. STUDY DESIGN After magnetic resonance imaging and rectal endoscopic sonographic evaluation of symptomatic colorectal endometriosis, 40 consecutive women requiring colorectal resection were included in this study. Symptom questionnaires were completed before and after the procedure. Perioperative complications and linear intensity scores for several gynecologic and digestive symptoms were recorded. RESULTS Thirty-six women (90%) underwent laparoscopic segmental colorectal resection and 4 required laparoconversion. Major complications occurred in 4 cases (10%), including 3 rectovaginal fistulae and 1 pelvic abscess. Transient urinary dysfunction occurred in 7 women (17.5%). Median follow-up after colorectal resection was 15 months (3-22 months). Median overall preoperative and postoperative pain scores were 8 +/- 1 (range 4-10) and 2 +/- 2 (0-10), respectively ( P < .0001). Nonmenstrual pelvic pain ( P = .0001), dysmenorrhea ( P < .0001), dyspareunia ( P = .0001), and pain on defecation ( P < .0005) were improved by colorectal resection. Lower back pain and asthenia were not improved. CONCLUSION Our results suggest that laparoscopic segmental colorectal resection for endometriosis is feasible but carries a risk of major postoperative complications. Colorectal resection improved gynecologic and digestive symptoms, and the overall pain score.

Mechanisms for estrogen receptor expression in human cancer.

Abstract: Estrogen is a steroid hormone that has critical roles in reproductive development, bone homeostasis, cardiovascular remodeling and brain functions. However, estrogen also promotes mammary, ovarian and endometrial tumorigenesis. Estrogen antagonists and drugs that reduce estrogen biosynthesis have become highly successful therapeutic agents for breast cancer patients. The effects of estrogen are largely mediated by estrogen receptor (ER) α and ERβ, which are members of the nuclear receptor superfamily of transcription factors. The mechanisms underlying the aberrant expression of ER in breast cancer and other types of human tumors are complex, involving considerable alternative splicing of ERα and ERβ, transcription factors, epigenetic and post-transcriptional regulation of ER expression. Elucidation of mechanisms for ER expression may not only help understand cancer progression and evolution, but also shed light on overcoming endocrine therapy resistance. Herein, we review the complex mechanisms for regulating ER expression in human cancer.

Resistance to endocrine therapy in breast cancer: molecular mechanisms and future goals.

Abstract: The majority of breast cancers (BCs) are characterized by the expression of estrogen receptor alpha (ERα+). ERα acts as ligand-dependent transcription factor for genes associated with cell survival, proliferation, and tumor growth. Thus, blocking the estrogen agonist effect on ERα is the main strategy in the treatment of ERα+ BCs. However, despite the development of targeted anti-estrogen therapies for ER+ BC, around 30–50% of early breast cancer patients will relapse. Acquired resistance to endocrine therapy is a great challenge in ER+ BC patient treatment. Anti-estrogen resistance is a consequence of molecular changes, which allow for tumor growth irrespective of estrogen presence. Those changes may be associated with ERα modifications either at the genetic, regulatory or protein level. Additionally, the activation of alternate growth pathways and/or cell survival mechanisms can lead to estrogen-independence and endocrine resistance. This comprehensive review summarizes molecular mechanisms associated with resistance to anti-estrogen therapy, focusing on genetic alterations, stress responses, cell survival mechanisms, and cell reprogramming.