Abstract 4143: Identification of molecular targets for conservative management of early stage, low-grade endometrial cancer through compartment-specific transcriptome profiling

Endometrial cancer is the most common gynecologic malignancy in the United States and the sixth most common cancer in women worldwide. Fortunately, most women who develop endometrial cancer have low-grade early-stage endometrioid carcinomas, and simple hysterectomy is curative. Unfortunately, 15% of women with endometrial cancer will develop high-risk histologic tumors including uterine carcinosarcoma or high-grade endometrioid, clear cell, or serous carcinomas. These high-risk histologic tumors account for more than 50% of deaths from this disease. In this review, we will highlight the biologic differences between low- and high-risk carcinomas with a focus on the cell of origin, early precursor lesions including atrophic and proliferative endometrium, and the potential role of stem cells. We will discuss treatment, including standard of care therapy, hormonal therapy, and precision medicine-based or targeted molecular therapies. We will also discuss the impact and need for model systems. The molecular underpinnings behind this high death to incidence ratio are important to understand and improve outcomes.

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CTNNB1 (beta-catenin) mutation identifies low grade, early stage endometrial cancer patients at increased risk of recurrence

Modern Pathology ◽

10.1038/modpathol.2017.15 ◽

2017 ◽

Vol 30 (7) ◽

pp. 1032-1041 ◽

Cited By ~ 58

Author(s):

Katherine C Kurnit ◽

Grace N Kim ◽

Bryan M Fellman ◽

Diana L Urbauer ◽

Gordon B Mills ◽

...

Keyword(s):

Endometrial Cancer ◽

Cancer Patients ◽

Early Stage ◽

Low Grade ◽

Beta Catenin ◽

Risk Of Recurrence ◽

Increased Risk ◽

Early Stage Endometrial Cancer

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Endometrial Cancer: What Is New in Adjuvant and Molecularly Targeted Therapy?

Obstetrics and Gynecology International ◽

10.1155/2010/749579 ◽

2010 ◽

Vol 2010 ◽

pp. 1-11 ◽

Cited By ~ 28

Author(s):

Flora Zagouri ◽

George Bozas ◽

Eftichia Kafantari ◽

Marinos Tsiatas ◽

Nikitas Nikitas ◽

...

Keyword(s):

Endometrial Cancer ◽

Metastatic Disease ◽

Cancer Biology ◽

Early Stage ◽

Single Agent ◽

Postoperative Management ◽

Low Grade ◽

Early Stage Disease ◽

High Risk Factors ◽

Staging Surgery

Endometrial cancer is the most common gynaecological cancer in western countries. Radiotherapy remains the mainstay of postoperative management, but accumulating data show that adjuvant chemotherapy may display promising results after staging surgery. The prognosis of patients with metastatic disease remains disappointing with only one-year survival. Progestins represent an effective option, especially for those patients with low-grade estrogen and/or progesterone receptor positive disease. Chemotherapy using the combination of paclitaxel, doxorubicin, and cisplatin is beneficial for patients with advanced or metastatic disease after staging surgery and potentially for patients with early-stage disease and high-risk factors. Toxicity is a point in question; however, the combination of paclitaxel with carboplatin may diminish these concerns. In women with multiple medical comorbidities, single-agent chemotherapy may be better tolerated with acceptable results. Our increased knowledge of the molecular aspects of endometrial cancer biology has paved the way for clinical research to develop novel targeted antineoplastic agents (everolimus, temsirolimus, gefitinib, erlotinib, cetuximab, trastuzumab, bevacizumab, sorafenib) as more effective and less toxic options. Continued investigation into the molecular pathways of endometrial cancer development and progression will increase our knowledge of this disease leading to the discovery of novel, superior agents.

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Ovarian Conservation and Overall Survival in Young Women With Early-Stage Low-Grade Endometrial Cancer

Obstetrics and Gynecology ◽

10.1097/aog.0000000000001647 ◽

2016 ◽

Vol 128 (4) ◽

pp. 761-770 ◽

Cited By ~ 32

Author(s):

Koji Matsuo ◽

Hiroko Machida ◽

Donna Shoupe ◽

Alexander Melamed ◽

Laila I. Muderspach ◽

...

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

Young Women ◽

Early Stage ◽

Low Grade ◽

Ovarian Conservation

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Surgical treatment and fertility perservation in endometrial cancer

Radiology and Oncology ◽

10.2478/raon-2021-0009 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Nina Kovacevic

Keyword(s):

Endometrial Cancer ◽

Standard Treatment ◽

Early Stage ◽

Hormonal Treatment ◽

Signs And Symptoms ◽

Treatment Modalities ◽

Low Grade ◽

Minimally Invasive Approach ◽

Invasive Approach ◽

Node Biopsy

Abstract Background Endometrial cancer (EC) represents a high health burden in Slovenia and worldwide. The incidence is increasing due to lifestyle and behavioural risk factors such as obesity, smoking, oestrogen exposure and aging of the population. In many cases, endometrial cancer is diagnosed at an early stage due to obvious signs and symptoms. The standard treatment is surgery with or without adjuvant therapy, depending on the stage of the disease and the risk of recurrence. However, treatment modalities have changed in the last decades, considerably in the extent of lymphadenectomy. Conclusions The gold standard of treatment for is surgery, which may be the only treatment modality in the early stages of low-grade tumours. In recent years, a minimally invasive approach with sentinel node biopsy (SNB) has been proposed. A conservative approach with hormonal treatment is used if fertility preservation is desired. If EC is in advance stage, high-risk histology, or high grade, radiotherapy, chemotherapy, or a combination of both is recommended.

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Abstract PO049: Compartment-specific profiling for evaluation of disrupted signaling in early stage, low-grade endometrial cancer

10.1158/1557-3265.endomet20-po049 ◽

2021 ◽

Author(s):

Qian Zhang ◽

Xiaoping Su ◽

Joseph Celestino ◽

Ying Yuan ◽

Samuel C. Mok ◽

...

Keyword(s):

Endometrial Cancer ◽

Early Stage ◽

Low Grade

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Baseline Serum HE4 But Not Tissue HE4 Expression Predicts Response to the Levonorgestrel-Releasing Intrauterine System in Atypical Hyperplasia and Early Stage Endometrial Cancer

Cancers ◽

10.3390/cancers12020276 ◽

2020 ◽

Vol 12 (2) ◽

pp. 276 ◽

Cited By ~ 1

Author(s):

Roya Behrouzi ◽

Neil A. J. Ryan ◽

Chloe E. Barr ◽

Abigail E. Derbyshire ◽

Y. Louise Wan ◽

...

Keyword(s):

Endometrial Cancer ◽

Early Stage ◽

Smoking Status ◽

Histological Grade ◽

Menopausal Status ◽

Tissue Expression ◽

Atypical Hyperplasia ◽

Low Grade ◽

Baseline Serum ◽

Early Stage Endometrial Cancer

The levonorgestrel-releasing intrauterine system (LNG-IUS) is a conservative management option for atypical hyperplasia (AH) and low grade early stage endometrial cancer (EEC), but around 1 in 3 patients fail to respond to treatment. The aim of this study was to investigate if serum and/or tissue HE4 expression could predict response to LNG-IUS therapy. Patients with AH or presumed Stage I EEC had serum and endometrial samples taken at baseline and at 3-month intervals over 12 months post-insertion of LNG-IUS. 74 patients were recruited and baseline demographics recorded. Of 57 patients for whom response was histologically determinable, 39 (68%) were responders and 18 (32%) non-responders. Mean baseline serum HE4 was significantly lower in responders (62.1 ± 1.1 pM, 95% confidence interval (CI) 52.7–73.2), compared to non-responders (125.6 ± 1.3 pM, 95% CI 74.5–211.7, p = 0.014), including when considering age, BMI, menopausal status, smoking status, and histological grade as covariables (p = 0.005). Baseline tissue HE4 expression was not significantly different in responders compared to non-responders (p = 0.999). Responders showed a significant mean reduction (−9.8 ± 3.4%, 95% CI −16.7 to −2.8%, p = 0.008) in serum HE4 between baseline and 3 months (p = 0.008), whereas non-responders showed no significant change (p = 0.676). Neither responders nor non-responders showed a significant percentage change in serum HE4 from baseline beyond 3 months (p > 0.05). Change in serum HE4 between baseline and 3 and 6 months and tissue HE4 tissue expression between baseline and 3, 6, and 12 months was not significantly different in responders compared to non-responders (p > 0.05). This study suggests that baseline serum HE4, but not baseline tissue HE4 expression, is independently predictive of response to the LNG-IUS and could be used to guide management decisions.

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