Endometrial Intraepithelial Neoplasia Research Articles

BPI24-011: Impact of Obesity on Sentinel Lymph Node Mapping in Patients With Endometrial Intraepithelial Neoplasia Undergoing Robotic Surgery.

BPI24-011: Impact of Obesity on Sentinel Lymph Node Mapping in Patients With Endometrial Intraepithelial Neoplasia Undergoing Robotic Surgery.

46. Endometrial Intraepithelial Neoplasia in a 14-year-old Adolescent Presenting with Heavy Menstrual Bleeding

46. Endometrial Intraepithelial Neoplasia in a 14-year-old Adolescent Presenting with Heavy Menstrual Bleeding

Abstract A021: Pilot study of daily exemestane in patients with Endometrial Intraepithelial Neoplasia (EIN) or grade 1 endometrial cancer

Abstract Introduction: The purpose of this study is to evaluate exemestane, an aromatase inhibitor, as a potential agent for the chemoprevention of endometrial cancer. Experimental procedures: This is a multi-center, phase IIA, single arm ‘window of opportunity’ pilot study of 25 mg per day of exemestane for 21-42 days in postmenopausal patients undergoing hysterectomy for endometrial intraepithelial neoplasia (EIN) or low-grade endometrial cancer. The primary objective is to determine if there is a decrease in proliferation index, measured by percent Ki-67 expression in endometrial tissue, from pre-treatment to post-exposure. Results of Ki-67 are compared with a historic control cohort of tumors from patients matched by preoperative histologic diagnosis, age, BMI category. Specimens from the historic control cohort included a preoperative endometrial biopsy as well as a surgical specimen, separated in time by less than 42 days. Secondary outcomes include comparison of Ki67 to historic controls, circulating serum estradiol and progesterone levels, pathologic response, tissue biomarkers, safety and adverse effects. Summary of Data: Forty patients accrued to the study between January of 2018 and March of 2021. The mean age was 63 (range 52-75). Thirty-nine patients (97.5%) self identifiedself-identified as white; 1 patient (2.5%) identified as Asian. The mean BMI was 40.3 (SD 9.75, range 22.8-60.5). Preoperative diagnoses included EIN, grade 1 endometrial adenocarcinoma, and grade 2 endometrial adenocarcinoma in 11 (27.5%), 26 (65%), and 3 (7.5%) patients respectively. Thirty-nine patients (97.5%) were compliant with exemestane dosing. All patients completed the study and no patients discontinued or interrupted therapy due to treatment related adverse events. Thirty-eight patients had evaluable specimens for both pre and post-treatment Ki-67 analysis. Median Ki-67 score decreased from 40.7% [IQR (33.9%, 50.3] at baseline to 18.1% [IQR (8.8%, 31.8%)]. This represents a median absolute change from baseline of -20.4% [IQR (-29.9, -6.7), p<0.001]. In total, percentage of Ki-67 in tumor cells declined in 31 patients and increased in 7 patients. In the historic control cohort, patients also had a decrease in Ki-67 score with a median absolute change from baseline of -6.7% [IQR (-12.7%, -1.3%), p<0.001]. However, the decrease in Ki-67 was greater in the study patients than the matched historic controls, with a median difference between the groups of -13.4% [IQR= (-23.3%, 6.9%), p=0.0095]. Serum estradiol levels did not change significantly between baseline and post-treatment (p=0.16). There was a small but significant increase from baseline to post-treatment in serum progesterone (0.14 ng/mL vs 0.37 ng/mL, p<0.001). Conclusion: In this pilot window of opportunity study, exemestane demonstrates anti-proliferative effects in endometrial intraepithelial neoplasia and low-grade endometrial cancer. This agent warrants further evaluation for the chemoprevention of endometrial cancer. Citation Format: Britt K. Erickson, Lisa Barrioullet, Rebecca C. Arend, Dina El-Rayes, Mahmoud Khalifa, Amy Skubitz, Kristin Boylan, Andrew Nelson, Bharat Thyagarajan, Thomas Havighurst, Richard Chappell, Eileen Dimond, Katina Deshong, Goli Samimi, Eva Szabo, Howard Bailey. Pilot study of daily exemestane in patients with Endometrial Intraepithelial Neoplasia (EIN) or grade 1 endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A021.

Machine learning for prediction of concurrent endometrial carcinoma in patients diagnosed with endometrial intraepithelial neoplasia

ObjectiveTo identify predictive clinico-pathologic factors for concurrent endometrial carcinoma (EC) among patients with endometrial intraepithelial neoplasia (EIN) using machine learning. Methodsa retrospective analysis of 160 patients with a biopsy proven EIN. We analyzed the performance of multiple machine learning models (n = 48) with different parameters to predict the diagnosis of postoperative EC. The prediction variables included: parity, gestations, sampling method, endometrial thickness, age, body mass index, diabetes, hypertension, serum CA-125, preoperative histology and preoperative hormonal therapy. Python ‘sklearn’ library was used to train and test the models. The model performance was evaluated by sensitivity, specificity, PPV, NPV and AUC. Five iterations of internal cross-validation were performed, and the mean values were used to compare between the models. ResultsOf the 160 women with a preoperative diagnosis of EIN, 37.5% (60) had a post-op diagnosis of EC. In univariable analysis, there were no significant predictors of EIN. For the five best machine learning models, all the models had a high specificity (71%–88%) and a low sensitivity (23%–51%). Logistic regression model had the highest specificity 88%, XG Boost had the highest sensitivity 51%, and the highest positive predictive value 62% and negative predictive value 73%. The highest area under the curve was achieved by the random forest model 0.646. ConclusionsEven using the most elaborate AI algorithms, it is not possible currently to predict concurrent EC in women with a preoperative diagnosis of EIN. As women with EIN have a high risk of concurrent EC, there may be a value of surgical staging including sentinel lymph node evaluation, to more precisely direct adjuvant treatment in the event EC is identified on final pathology.

Defining the relationship between ovarian adult granulosa cell tumors and synchronous endometrial pathology: Does ovarian tumor size correlate with endometrial cancer?

The main feature of adult granulosa cell tumors (AGCT) is their capacity to secrete hormones, with nearly all of them capable of synthesizing oestradiol. The primary goal of this study is to identify synchronized endometrial pathologies, particularly endometrial cancer, in AGCT patients who had undergone a hysterectomy. The study cohort comprised retrospectively of 316 AGCT patients from 10 tertiary gynecological oncology centers. AGCT surgery consisted of bilateral salpingo-oophorectomy, hysterectomy, peritoneal cytology, omentectomy, and the excision of any suspicious lesion. The median tumor size value was used to define the relationship between tumor size and endometrial cancer. The relationship between each value and endometrial cancer was evaluated. Endometrial intraepithelial neoplasia, or hyperplasia with complex atypia, was detected in 7.3% of patients, and endometrial cancer in 3.1% of patients. Age, menopausal status, tumor size, International Federation of Gynecology and Obstetrics stage, ascites, and CA-125 level were not statistically significant factors to predict endometrial cancer. There was no endometrial cancer under the age of 40, and 97.8% of women diagnosed with endometrial hyperplasia were over the age of 40. During the menopausal period, the endometrial cancer risk was 4.5%. Developing endometrial cancer increased to 12.1% from 3.2% when the size of the tumor was >150 mm in menopausal patients (p = 0.036). Endometrial hyperplasia, or cancer, occurs in approximately 30% of AGCT patients. Patients diagnosed with AGCT, especially those older than 40 years, should be evaluated for endometrial pathologies. There may be a relationship between tumor size and endometrial cancer, especially in menopausal patients.

Levonorgestrel-releasing intrauterine device therapy vs oral progestin treatment for reproductive-aged patients with endometrial intraepithelial neoplasia: a systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to examine outcomes of patients with endometrial intraepithelial neoplasia treated with oral progestins or a levonorgestrel-releasing intrauterine device (IUD). We conducted a systematic review across 5 databases to examine outcomes of progestational treatment (oral progestins or levonorgestrel-releasing IUD) for patients with endometrial intraepithelial neoplasia. The primary outcome was the best complete response rate within 12 months of primary progestational treatment. Sensitivity analyses were performed by removing studies with extreme effect sizes. Secondary outcomes included the pooled pregnancy rate. We identified 21 eligible studies, including 824 premenopausal patients with endometrial intraepithelial neoplasia, for our meta-analysis. Among these, 459 patients received oral progestin, and 365 patients received levonorgestrel-releasing IUD as a primary progestational treatment. The pooled best complete response proportion within 12 months was 82% (95% confidence interval [CI] = 69% to 91%) following oral progestin treatment and 95% (95% CI = 81% to 99%) following levonorgestrel-releasing IUD treatment. After removing outlier studies, the pooled proportion was 86% (95% CI = 75% to 92%) for the oral progestin group and 96% (95% CI = 91% to 99%) for the levonorgestrel-releasing IUD group, with reduced heterogeneity. The pooled pregnancy rate was 50% (95% CI = 35% to 65%) after oral progestin and 35% (95% CI = 23% to 49%) after levonorgestrel-releasing IUD treatment. This meta-analysis provides data on the effectiveness of oral progestins and levonorgestrel-releasing IUD treatment within 12 months of treatment among premenopausal patients with endometrial intraepithelial neoplasia. Although based on small numbers, the rate of pregnancy after treatment is modest. These data may be beneficial for selecting progestational therapies that allow fertility preservation for patients with endometrial intraepithelial neoplasia.

Predicting Progestin Therapy Response With PTEN, PAX2, and β-Catenin in Patients With Endometrioid Precancer.

This study investigates the predictive value of biomarkers PTEN, PAX2, and β-catenin for therapeutic outcomes in patients with atypical endometrial hyperplasia or endometrioid intraepithelial neoplasia undergoing progestin therapy. In a retrospective study of 128 patients, we analyzed a total of 351 endometrial biopsy samples and categorized outcomes into responders (absence of residual disease) and nonresponders (presence of residual disease). We found aberrant biomarker expression in pretreatment cases: 48% for PTEN, 65% for PAX2, and 36% for β-catenin. Approximately 77.3% of patients responded to progestin treatment, with nonresponders showing significantly higher initial PTEN loss (75.86% vs 39.79%, P < 0.001). Nonresponders also demonstrated significant PTEN loss (53.33% vs 20.55%, P < 0.001), PAX2 loss (57.33% vs 41.22%, P < 0.05), and β-catenin nuclear staining (53.45% vs 27.91%, P < 0.01) in follow-up samples. In addition, nonresponders exhibited lower recovery of intact PTEN and PAX2, along with higher β-catenin aberrancy in cases initially showing normal β-catenin levels. We conclude that persistent aberrant PTEN and PAX2 expression, coupled with emerging aberrant β-catenin in follow-ups, indicates a greater likelihood of treatment failure. Conversely, the absence of these aberrations suggests successful progestin therapy. Our findings highlight the utility of this 3-marker panel in assessing residual disease status and predicting progestin treatment outcomes, thus offering critical insights for patient management.

CXCR4 Expression and Cancer-associated Fibroblasts May Play an Important Role in the Invasion of Low-grade Endometrioid Carcinoma.

Well-differentiated endometrioid carcinoma (EC) is a low-grade cancer with relatively indolent behavior. However, even with well-differentiated histology, it sometimes tends to invade extensively and shows metastatic potential, suggesting that this is a group of cancers with heterogeneous behavior. In contrast, due to its tendency for younger onset, the treatment strategy for EC frequently considers fertility preservation, highlighting the need for a more accurate evaluation of myometrial invasion through biopsy and imaging diagnostics. We previously reported the involvement of the CXCR4-CXCL12 and CXCL14 axes in EC invasion. Accordingly, we investigated whether CXCR4 expression could reflect invasive potential and explored its interaction with cancer-associated fibroblasts that produce chemokines in the tumor microenvironment. Immunohistochemical expression of CXCR4 was assessed in 71 cases of EC (14 of EC confined to the endometrium and 57 of myoinvasive EC), 6 cases of endometrial intraepithelial neoplasia, and 42 cases of noncarcinomatous conditions. CXCR4 expression was significantly higher in myoinvasive EC than in noncancerous conditions, endometrial intraepithelial neoplasia, and endometrium-confined EC. By univariate and multivariate analysis, CXCR4 expression significantly reflected myometrial invasion. CXCR4 expression in the biopsied and resected specimens correlated weakly positively. Invasion and wound-healing assays were performed culturing an EC cell line in a cancer-associated fibroblast-conditioned medium. The invasion and wound-healing potentials were dependent on CXCR4 and cancer-associated fibroblast. Our study demonstrated that CXCR4 expression is an independent factor in myometrial invasion and can support diagnostic evaluation before treatment in the biopsy sample.

Fertility After Endometrial Intraepithelial Neoplasia and Early Endometrial Cancer: Ovulation Induction May Shorten Time to Conception.

The purpose of this study was to determine whether utilization of assisted reproductive technology following clearance of endometrial intraepithelial neoplasia (EIN) or early endometrial cancer (EC)shortens time to conception (TTC) and reduces recurrence. Patients aged 18 to 45 with EIN or early EC who achieved pathologic response following progesterone treatment were identified via retrospective chart review. Study groups included patients who pursued ovulation induction (OI), in vitro fertilization (IVF), and spontaneous pregnancy. Primary outcomes were TTC and recurrence rate. Three hundred forty-six charts were reviewed, with 86 patients meeting inclusion criteria and 53 attempting pregnancy. Of those 53 patients, 11 became pregnant and seven had a live birth. Median times to pregnancy were 183days for IVF, 54days for OI, and 347days for spontaneous conception (p < 0.05). No differences were seen in recurrence or progression based on attempted pregnancy method, nor with duration of fertility treatment. Forty-two of 86 patients (49%) were lost to follow-up. For patients with a history of treated EIN or EC, OI may decrease TTC. Larger prospective studies are needed to definitively answer this question. Although no differences in recurrence or progression were identified, the significant loss to follow-up rate in this study is concerning and warrants further investigation.

The Impact of Surgical Delay: A Single Institutional Experience at the Epicenter of the COVID Pandemic Treatment Delays in Women with Endometrial Cancer and Endometrial Intraepithelial Hyperplasia

The spread of COVID-19 led to a lockdown in New York in March of 2020. Nonemergent surgeries were postponed, including oncologic procedures. The backlog of surgeries was addressed starting May 2020. Our goal was to examine the change in waiting times for endometrial cancer surgeries during the COVID-19 pandemic in our institution. Data on surgery incidence and waiting time was gathered for patients diagnosed with endometrial intraepithelial neoplasia and endometrial cancer. The association between days from diagnosis to surgery was adjusted for age, obesity, presence of comorbid conditions, race, smoking history and diagnosis and was examined using a general linear model. A total of 190 patients were identified for this retrospective study. Five subjects were missing information on race and were excluded from all analyses, resulting in 185 subjects in the final analyses. Mean waiting time during COVID-19 was 70.9 days (95%CI 55.0, 91.3), compared to 49.3 (95%CI 49.8, 63.8) days during the reference period. No significant associations were seen between the time and any of the clinical or demographic factors.

The clinical and reproductive outcomes of endometrial intraepithelial neoplasia: experience of 117 cases

The clinical and reproductive outcomes of endometrial intraepithelial neoplasia: experience of 117 cases

Glandular Crowdings in Endometrial Polyps: Clinical Follow-Up and Possible Worrisome Features.

Interpretation of changes and premalignant lesions in endometrial polyps can be challenging. We evaluated the clinical course of patients with focal gland crowdings in endometrial polyps via repeat biopsies and searched for possible morphological findings in the initial biopsy that may foresee a premalignant course. Specimens diagnosed as endometrial polyp and focal gland crowding in patients who had a repeat biopsy in a 1-year period were reexamined. Morphological findings in the initial biopsies were recorded. The group whose repeat biopsies were "premalignant or malignant" (Group 1), and the group with "benign" repeat biopsies (Group 2) were compared. "Endometrial polyp and gland crowdings" was diagnosed in 115 specimens of which 38 patients had repeat biopsies. Among these 8 (21%) were diagnosed as "endometrial intraepithelial neoplasia (EIN)" (Group 1) and 30 (79%) as "benign" (Group 2). Morphological features in the initial biopsies were evaluated; PAX2 loss was 6 of 8 (75%) for Group 1 and 7 of 30 (23%) for Group 2 (P = .020), and altered epithelial cytological features were present in 5 of 8 (62%) versus 4 of 30 (13%) (P = .015), both significantly higher in Group 1. Dark intraluminal secretion, intraluminal histiocytes, intraglandular epithelial proliferation, and mean diameter of crowded gland areas were not statistically different between the 2 groups. "Focal gland crowdings" in endometrial polyps do carry a risk of EIN in subsequent biopsies. We suggest that the loss/decrease of PAX2 and altered epithelial cytological features in these areas in the initial biopsy are indicative of a premalignant course.

Abstract A132: Time to treatment by neighborhood among endometrial intraepithelial neoplasia and endometrial cancer patients

Abstract Objective: To examine interval wait time for surgery in EIN and Endometrial Cancer patients at a single institution and identify potential disparities in access to care Methods: At this single institution, five priority neighborhoods where medically underserved populations reside have been designated from a Community Health Needs Assessment. We performed a retrospective chart review of patients with EIN or endometrial cancer at a single institution between 2016-2019. Patients from one of five priority neighborhoods were compared with patients from other zip codes within the same state. Results: 100 patients from priority neighborhoods and 104 patients from other neighborhoods within the same state were identified. Mean age was similar (59.74 vs 58.15 yrs, p 0.372) and rates of private insurance status were similar (66% vs 52%, p 0.08). Priority neighborhood patients were more likely to identify as Black or Hispanic (30.0% vs 4.81%; 18.0% vs 0%, p &amp;lt;0.001), and were more likely to speak a non-English primary language (19.0% vs 2.88%, p 0.005). Priority neighborhood patients had a higher Charlson Deyo co-morbidity score (2.44 vs 2.49, p 0.809). Patients had a similar rates of advanced stage disease (Stage III or IV 16 vs 16, p 0.213) and histologic subtype (Endometrioid 47.5% vs 59.6%; Serous or Clear Cell 13.46% vs 14.75%, p 0.962). The mean interval to treatment by primary surgery from referral visit was 68.9 days for non-priority neighborhood patients compared to 80.12 days for priority neighborhood patients (p 0.478). In univariate analysis, race/ethnicity, primary language, and insurance status were not significant factors impacting time to treatment.   Conclusion: Interval wait time to primary surgery among a single institution cohort was longer for priority neighborhood patients. This study highlights potential barriers to healthcare access that are unaddressed by current systems. Citation Format: Victoria Wang, Hadley Reid, Andrea Pelletier, Trinity Russell, Lucy Chen, Reagan Marsh, Colleen Feltmate, Alexi Wright, Kevin Elias. Time to treatment by neighborhood among endometrial intraepithelial neoplasia and endometrial cancer patients [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A132.

Management of Endometrial Intraepithelial Neoplasia or Atypical Endometrial Hyperplasia

(Abstracted from Obstet Gynecol 2023;142(3)) Endometrial cancer incidence is rising in the United States and disproportionally affects patients based on race, geography, and socioeconomic status. Endometrial intraepithelial neoplasia (EIN) or atypical endometrial hyperplasia (AEH) is often precursor lesions to adenocarcinoma in the endometrium.

Association of Body Mass Index With Early Age at Diagnosis of Endometrial Intraepithelial Neoplasia

(Abstracted from Gynecol Oncol 2023;175:15–19) The development of endometrial intraepithelial neoplasia (EIN), a precursor lesion to endometrioid endometrial cancer, is related to prolonged and unopposed excess estrogen stimulation in the endometrium. The 2 conditions are frequently diagnosed concurrently.

Age as a Predictor of Time to Response for Patients Undergoing Medical Management of Endometrial Cancer

Objective: To explore the pathologic response rate to primary progesterone treatment in patients with Endometrial Intraepithelial Neoplasia (EIN) and early-stage endometrioid-type Endometrial Adenocarcinoma (EAC). Methods: Retrospective chart data were collected for patients with either EIN or EAC receiving primary progesterone treatment between 2015 and 2022. The presence of complete or partial response, time to response, and other demographic and treatment factors were recorded to determine independent predictors of response to progestin treatment. Results: In total, 112 women who were diagnosed with EIN or EAC were treated with upfront progestin therapy, of whom 79 had sufficient follow-up to assess response. Fifty patients (63%) responded, of whom 10 (20%) ultimately relapsed. Response was more robust among patients with EIN (79%, n = 33) compared with patients who had cancer (46%, n = 17). The median time to respond was 5.8 months overall. Diagnosis of EIN, younger age at diagnosis, and any pathologic evidence of progesterone effect were all predictors of treatment response. Younger patients had a significantly shorter time to partial or complete response with a median time to response of 5.9 months in patients ≤ 45 and 13.8 months in patients &gt; 45. Conclusion: Our study demonstrated a lower overall response rate (63%) than reported in previous studies, especially for patients with cancer (46%). Younger patients had a significantly shorter time to respond than older patients. Pathologic progesterone effect observed at any time during treatment was a significant predictor of treatment response regardless of diagnosis and could serve as an early predictor of response to therapy.

Predictors of response to progesterone therapy in pre-menopausal women with endometrial intraepithelial neoplasia (1136)

Predictors of response to progesterone therapy in pre-menopausal women with endometrial intraepithelial neoplasia (1136)

Matchmaker, matchmaker: Pairing mismatch repair proteins with diagnosis of concurrent cancer on endometrial intraepithelial neoplasia (EIN) biopsy (2277)

Matchmaker, matchmaker: Pairing mismatch repair proteins with diagnosis of concurrent cancer on endometrial intraepithelial neoplasia (EIN) biopsy (2277)

Increasing use and outcomes of oral and intrauterine progestin therapy for premenopausal women with endometrial intraepithelial neoplasia (2198)

Increasing use and outcomes of oral and intrauterine progestin therapy for premenopausal women with endometrial intraepithelial neoplasia (2198)

Safety of same-day discharge after minimally invasive hysterectomy for endometrial cancer and endometrial intraepithelial neoplasia among patients with morbid obesity (1187)

Safety of same-day discharge after minimally invasive hysterectomy for endometrial cancer and endometrial intraepithelial neoplasia among patients with morbid obesity (1187)