Molecular classification of endometrial carcinomas: a singleinstitution review (084)

Rios-Doria, Eric; Abu‐Rustum, Nadeem R.; Leitao, Mario M.; Alektiar, Kaled M.; Makker, Vicky; Liu, Ying; Zamarin, Dmitriy; Friedman, Claire F.; Aghajanian, Carol; Ellenson, Lora Hedrick; Weigelt, Britta; Mueller, Jennifer J.

doi:10.1016/s0090-8258(22)01309-9

Cited by 7 publications

(21 citation statements)

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“…11,12 The feasibility and validity of this surrogate algorithm has been confirmed in numerous studies, including data from clinical trials, consistently demonstrating the prognostic association of these molecular subtypes with outcome. 11,[13][14][15][16] Importantly, it has been shown that the prognostic relevance of the molecular classification extends to other histologic subtypes including clear cell carcinoma, carcinosarcoma and un/ dedifferentiated carcinoma, however that the prevalence of each molecular subtype varies across histologic types. 14,[17][18][19][20][21][22] With the introduction of clinical sequencing, our team has demonstrated that clinical tumor-normal sequencing data obtained from an Food and Drug Administration (FDA)-authorized cancer gene panel (MSK-IMPACT) 23 can be utilized for the molecular classification of EC across histologic types.…”

Section: Molecular Subtypes Of Ec: the Beginning And Implementation I...mentioning

confidence: 99%

“…11,[13][14][15][16] Importantly, it has been shown that the prognostic relevance of the molecular classification extends to other histologic subtypes including clear cell carcinoma, carcinosarcoma and un/ dedifferentiated carcinoma, however that the prevalence of each molecular subtype varies across histologic types. 14,[17][18][19][20][21][22] With the introduction of clinical sequencing, our team has demonstrated that clinical tumor-normal sequencing data obtained from an Food and Drug Administration (FDA)-authorized cancer gene panel (MSK-IMPACT) 23 can be utilized for the molecular classification of EC across histologic types. 14 The integration of molecular and IHC data for classification (Figure 1), including POLE mutation status, sequencing-based MSIsensor score and/or MMR IHC for the MSI-H subtype classification and TP53 mutation and/or MDM2 amplification status for the CN-H/TP53 abnormal (abn) molecular subtype, had a near perfect agreement with the conventional surrogate approach.…”

Section: Molecular Subtypes Of Ec: the Beginning And Implementation I...mentioning

confidence: 99%

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Moving into the modern era of molecular classification for endometrial cancer

Dagher,

Liu,

Mueller

et al. 2023

Journal of Surgical Oncology

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The molecular subtypes of endometrial carcinoma (EC) were first described by The Cancer Genome Atlas (TCGA) a decade ago. Using surrogate approaches, the molecular classification has been demonstrated to be prognostic across EC patients and to have predictive implications. Starting in 2020, the molecular classification has been incorporated into multiple guidelines as part of the risk assessment and most recently into the International Federation of Gynecology and Obstetrics (FIGO) staging. This review article discusses the implementation of the EC molecular classification into clinical practice, the therapeutic implications, and the molecular and clinical heterogeneity of the EC molecular subtypes.

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Section: Molecular Subtypes Of Ec: the Beginning And Implementation I...mentioning

confidence: 99%

Section: Molecular Subtypes Of Ec: the Beginning And Implementation I...mentioning

confidence: 99%

Moving into the modern era of molecular classification for endometrial cancer

Dagher,

Liu,

Mueller

et al. 2023

Journal of Surgical Oncology

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“…All 4 molecular subtypes consist of varying proportions of endometrial cancer histologies. Results presented at the 2022 SGO Annual Meeting on Women's Cancer; March 18-21, 2022; Phoenix, AZ 11. These results are preliminary and will be published in finalized form.…”

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confidence: 99%

“…10 Each molecular subtype has its own prognostic significance, with the POLE subtype associated with the best survival outcomes and the CN-H subtype associated with the poorest survival outcomes. 11 Although histology and stage are currently used to stratify patients for treatment and to predict outcomes, recent studies have found considerable histologic diversity within EC subtypes, underscoring the importance of the molecular classification of all EC tumors. 11 Molecular subtyping has informed significant therapeutic advancements in advanced/recurrent EC, as outlined in this review, and has been increasingly exploited for risk stratification for optimal personalized treatment.…”

mentioning

confidence: 99%

“…11 Although histology and stage are currently used to stratify patients for treatment and to predict outcomes, recent studies have found considerable histologic diversity within EC subtypes, underscoring the importance of the molecular classification of all EC tumors. 11 Molecular subtyping has informed significant therapeutic advancements in advanced/recurrent EC, as outlined in this review, and has been increasingly exploited for risk stratification for optimal personalized treatment. The largest cohort of patients with EC who have undergone complete molecular characterization was recently presented by investigators at Memorial Sloan Kettering Cancer Center (Figure 1).…”

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confidence: 99%

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Current Evidence-Based Systemic Therapy for Advanced and Recurrent Endometrial Cancer

Gordhandas

Zammarrelli

Rios-Doria

et al. 2023

Journal of the National Comprehensive Cancer Network

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Endometrial cancer (EC) is the most common gynecologic malignancy, with worldwide increasing incidence and disease-associated mortality. Although most patients with EC are diagnosed with early-stage disease, systemic treatment options for patients with advanced or recurrent EC have historically been limited. EC-focused clinical trials and the ensuing therapeutic landscape have expanded since The Cancer Genome Atlas (TCGA) identified 4 distinct EC subgroups associated with differential survival. This endeavor revolutionized our understanding of the genomic characterization of EC as well as molecular drivers of this heterogeneous malignancy, leading to precision oncology approaches to therapeutics and advancement in treatment options. This review describes the current status of and recent advancements in therapeutic options for patients with advanced and recurrent EC. The NCCN Guidelines for Uterine Neoplasms provide detailed recommendations regarding the diagnosis, workup, and management of EC.

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Pathogenic germline variants in patients with endometrial cancer of diverse ancestry

Liu,

Gordhandas,

Arora

et al. 2023

Cancer

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BackgroundRacial disparities in outcomes exist in endometrial cancer (EC). The contribution of ancestry‐based variations in germline pathogenic variants (gPVs) is unknown.MethodsGermline assessment of ≥76 cancer predisposition genes was performed in patients with EC undergoing tumor‐normal Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets sequencing from January 1, 2015 through June 30, 2021. Self‐reported race/ethnicity and Ashkenazi Jewish ancestry data classified patients into groups. Genetic ancestry was inferred from Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets. Rates of gPV and genetic counseling were compared by ancestry.ResultsAmong 1625 patients with EC, 216 (13%) had gPVs; 15 had >1 gPV. Rates of gPV varied by self‐reported ancestry (Ashkenazi Jewish, 40/202 [20%]; Asian, 15/124 [12%]; Black/African American (AA), 12/171 [7.0%]; Hispanic, 15/124 [12%]; non‐Hispanic (NH) White, 129/927 [14%]; missing, 5/77 [6.5%]; p = .009], with similar findings by genetic ancestry (p < .001). We observed a lower likelihood of gPVs in patients of Black/AA (odds ratio [OR], 0.44; 95% CI, 0.22–0.81) and African (AFR) ancestry (OR, 0.42; 95% CI, 0.18–0.85) and a higher likelihood in patients of Ashkenazi Jewish genetic ancestry (OR, 1.62; 95% CI; 1.11–2.34) compared with patients of non‐Hispanic White/European ancestry, even after adjustment for age and molecular subtype. Somatic landscape influenced gPVs with lower rates of microsatellite instability‐high tumors in patients of Black/AA and AFR ancestry. Among those with newly identified gPVs (n = 114), 102 (89%) were seen for genetic counseling, with lowest rates among Black/AA (75%) and AFR patients (67%).ConclusionsIn those with EC, gPV and genetic counseling varied by ancestry, with lowest rates among Black/AA and AFR patients, potentially contributing to disparities in outcomes given implications for treatment and cancer prevention.Plain Language Summary Black women with endometrial cancer do worse than White women, and there are many reasons for this disparity. Certain genetic changes from birth (mutations) can increase the risk of cancer, and it is unknown if rates of these changes are different between different ancestry groups. Genetic mutations in 1625 diverse women with endometrial cancer were studied and the lowest rates of mutations and genetic counseling were found in Black and African ancestry women. This could affect their treatment options as well as their families and may make disparities worse.

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Molecular classification of endometrial carcinomas: a singleinstitution review (084)

Cited by 7 publications

References 0 publications

Moving into the modern era of molecular classification for endometrial cancer

Moving into the modern era of molecular classification for endometrial cancer

Current Evidence-Based Systemic Therapy for Advanced and Recurrent Endometrial Cancer

Pathogenic germline variants in patients with endometrial cancer of diverse ancestry

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