scholarly journals Uterine serous carcinoma: key advances and novel treatment approaches

2021 ◽  
pp. ijgc-2021-002753
Author(s):  
J Stuart Ferriss ◽  
Britt K Erickson ◽  
Ie-Ming Shih ◽  
Amanda N Fader
Keyword(s):  
Endometrial Cancer ◽  
Black Women ◽  
Treatment Options ◽  
Molecular Genetic ◽  
Serous Carcinoma ◽  
Cancer Syndrome ◽  
Her2 Positive ◽  
Incidence And Mortality ◽  
History Of ◽  
Uterine Serous Carcinoma

The incidence and mortality rates from endometrial cancer continue to increase worldwide, while rates in most other cancers have either plateaued or declined considerably. Uterine serous carcinoma represents a fraction of all endometrial malignancies each year, yet this histology is responsible for nearly 40% of all endometrial cancer-related deaths. These deaths disproportionately affect black women, who have higher rates of advanced disease at diagnosis. Molecular genetic analyses reveal major alterations including TP53 mutation, PIK3CA mutation/amplification, ERBB2 amplification, CCNE1 amplification, FBXW7 mutation/deletion, PPP2R1A mutation, and somatic mutations involving homologous recombination genes. Clinical risk factors for uterine serous carcinoma include advancing age, a history of breast cancer, tamoxifen usage, and the hereditary breast–ovarian cancer syndrome. Surgery remains the cornerstone of treatment. Recent advances in our understanding of uterine serous carcinoma molecular drivers have led to development of targeted therapeutics that promise improved outcomes for patients. Overexpression or amplification of HER2 in uterine serous carcinoma carries a poor prognosis; yet this actionable target has led to the incorporation of several anti-HER2 therapies, including trastuzumab which, when added to conventional chemotherapy, is associated with improved survival for women with advanced and recurrent HER2-positive disease. The combination of pembrolizumab and lenvatinib is also a promising targeted treatment strategy for women with uterine serous carcinoma, with a recent phase II study suggesting a 50% response rate in women with recurrent disease. Several trials examining additional targeted agents are ongoing. Despite years of stalled progress, meaningful, tailored treatment options are emerging for patients with this uncommon and biologically aggressive endometrial cancer subtype.

Is uterine serous carcinoma a part of hereditary breast cancer syndrome?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5587-5587
Author(s):  
Saeed Rafii ◽  
Philip Dawson ◽  
Sarah Williams ◽  
Jennifer S. Pascoe ◽  
James E. Nevin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Personal History ◽  
Tamoxifen Treatment ◽  
Serous Carcinoma ◽  
Cancer Syndrome ◽  
Younger Age ◽  
History Of ◽  
Uterine Serous Carcinoma ◽  
History Of Cancer

5587 Background: Whilst the association between breast cancer and uterine serous carcinoma (USC) is attributed to tamoxifen treatment, few studies have reported that this increased risk is independent of tamoxifen. Methods: To further investigate the relationship between breast cancer and USC, we retrospectively studied 216 patients from 5 hospital trusts in Birmingham, UK who were diagnosed with USC between 1993 and 2012. We collected personal history of cancer in these cases before or after USC diagnosis. In addition FIGO staging, clinical and survival data were collected from our local cancer registry and patients’ clinical records. Results: In this case series, 56 patients (25.9%) had personal history of at least one cancer before and 18 patients (8.3%) had history of at least one cancer after the diagnosis of USC. Within the group of patients with the history of cancer before the USC, 38 patients (68%, 17.5% of all cases) had personal history of breast cancer prior to the development of USC, higher than the UK expected age standardised relative incidence of breast cancer (350 in 100,000, CRUK 2006-2008). Although 27/38 cases (71%) had endocrine treatment for their primary breast cancer, 11/38 patients (29%) did not have any tamoxifen treatment due to hormone receptor negative breast cancer. Additionally the median age of breast cancer diagnosis for the hormone receptor negative group was significantly lower than those patients who had hormonal treatment for their breast cancer (56 vs. 64 years, p :0.036) compatible with the younger age at diagnosis expected of the familial (BRCA mutated) or triple negative breast cancer. Of 18 patients with a second cancer after diagnosis of USC, 6 patients (33%) were diagnosed with breast/ovarian cancer. This group also had no treatment with tamoxifen. Conclusions: Lack of exposure to tamoxifen and younger age at diagnosis in this subgroup suggest that other factors such as a common underlying genetic predisposition may be responsible for the development of both malignancies. We propose that at least a subgroup of USC may be a part of hereditary breast cancer syndrome. This may have implications in prevention (prophylactic hysterectomy) or trials of targeted treatments (PARP inhibitors) for a subgroup of USC patients.

Clinical application of polymorphic variants of the genes ESR1 and CYP2D6*4 in patients with breast and endometrial cancer

2017 ◽  
pp. 132-138
Author(s):  
O.V. Paliychuk ◽  
◽  
L.Z. Polishchuk ◽  
Z.I. Rossokha ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endometrial Cancer ◽  
Hormone Therapy ◽  
Molecular Genetic ◽  
Cancer Syndrome ◽  
Genetic Characteristics ◽  
Multiple Tumors ◽  
Receptor Status ◽  
Genetic Examination ◽  
The Impact

The objective: determining gene polymorphism features ERS1, CYP2D6 in patients with breast cancer (RHZ) and endometrial cancer (EC) and the impact assessment studied genetic characteristics compared to receptor status (immunohistochemical determination of expression levels of ER, PR) tumors and the results of the treatment. Patients and methods. article presents the results of complex clinical, morphological, clinical-genealogical, and molecular-genetic examination of 28 females: 19 patients with breast cancer (BC), 9 patients with endometrial cancer (EC), including 5 patients with primary-multiple tumors (PMT) with and without tumor pathology aggregation in families. Results. The It was determined that in patients’ families malignant tumors of breast, uterine body and/or ovaries prevail that corresponds to Lynch type II syndrome (family cancer syndrome). Molecular-genetic examination of genomic DNA of peripheral blood and histological sections for the presence of SNPs of ESR and CYP2D6*4 genes comparing with the results of immunohistochemical study of tumors for receptors ER and PR status have not found associations between these characteristics; although among EC patients the occurrence of genotypes 397ТТ and 351АА was significantly higher comparing with BC patients (55.55% and 10.5% for genotype 397ТТ,and 15.8% for genotype 351АА, respectively). At the same time the patients with BC and primary-multiple tumors (PMT) of female reproductive system organs (FRSO) that carried mutations in BRCA1 in all the cases demonstrated positive ER and PR receptor status and adverse combinations of polymorphous variants of the genes ESR1 (397СС, 397ТС) and CYP2D6*4 (1846G, 1846GA), suggesting combined effect of these factors on the development of malignant neoplasias of FRSO in families with positive family cancer history. In BC patients, receiving standard hormone therapy with tamoxifen, those, who had genotype 1846GG of the gene CYP2D6*4, in 3 patients (15.8%) of 19 (100%) patients disease recurrence was diagnosed. Conclusion. The obtained results allow clinical use of the assessment of polymorphism frequency of the genes ESR1 and CYP2D6*4 for selection of individual hormone therapy regimens schemes for BC patients, to increase efficacy of dispensary observation after finishing of special therapy for such patients, and also personalization of complex and combined treatment regimens. Key words: breast cancer, endometrial cancer, family cancer syndrome, single nucleotide polymorphisms (SNPs) of the genes ESR1, CYP2D6*4.

scholarly journals A 4-gene signature predicts prognosis of uterine serous carcinoma

2020 ◽  
Author(s):  
Hui Chen ◽  
Lingjun Li ◽  
Ping Qin ◽  
Hanzhen Xiong ◽  
Ruichao Chen ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Roc Curve ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
Functional Enrichment ◽  
Serous Carcinoma ◽  
Regression Analyses ◽  
Uterine Serous Carcinoma ◽  
Clinical Records

Abstract Background: Uterine serous carcinoma (USC) is an aggressive type of endometrial cancer that accounts for up to 40% of endometrial cancer deaths, creating an urgent need for prognostic biomarkers. Methods: USC RNA-Seq data and corresponding patients’ clinical records were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression datasets. Univariate cox, Lasso, and Multivariate cox regression analyses were conducted to forge a prognostic signature. Multivariable and univariable cox regression analysis and ROC curve evaluated the prediction efficiency both in the training and testing sets. Results: We uncovered 1385 genes dysregulated in 110 cases of USC tissue relative to 113 cases of normal uterine tissue. Functional enrichment analysis of these genes revealed the involvement of various cancer-related pathways in USC. A novel 4‐gene signature (KRT23, CXCL1, SOX9 and ABCA10) of USC prognosis was finally forged by serial regression analyses. Overall patient survival (OS) and recurrence-free survival (RFS) were significantly lower in the high-risk group relative to the low-risk group in both the training and testing sets. The area under the ROC curve of the 4-gene signature was highest among clinicopathological features in predicting OS and RFS. The 4-gene signature was found to be an independent prognostic indicator in USC and was a superior predictor of OS in early stage of USC. Conclusions: Our findings highlight the potential of the 4-gene signature as a guide for personalized USC treatment.

scholarly journals A 4-gene signature predicts prognosis of uterine serous carcinoma

2020 ◽  
Author(s):  
Hui Chen ◽  
Lingjun Li ◽  
Ping Qin ◽  
Hanzhen Xiong ◽  
Ruichao Chen ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Roc Curve ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
Functional Enrichment ◽  
Serous Carcinoma ◽  
Regression Analyses ◽  
Uterine Serous Carcinoma ◽  
Clinical Records

Abstract Background: Uterine serous carcinoma (USC) is an aggressive type of endometrial cancer that accounts for up to 40% of endometrial cancer deaths, creating an urgent need for prognostic biomarkers. Methods: USC RNA-Seq data and corresponding patients’ clinical records were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression datasets. Univariate cox, Lasso, and Multivariate cox regression analyses were conducted to forge a prognostic signature. Multivariable and univariable cox regression analysis and ROC curve evaluated the prediction efficiency both in the training and testing sets. Results: We uncovered 1385 genes dysregulated in 110 cases of USC tissue relative to 113 cases of normal uterine tissue. Functional enrichment analysis of these genes revealed the involvement of various cancer-related pathways in USC. A novel 4‐gene signature (KRT23, CXCL1, SOX9 and ABCA10) of USC prognosis was finally forged by serial regression analyses. Overall patient survival (OS) and recurrence-free survival (RFS) were significantly lower in the high-risk group relative to the low-risk group in both the training and testing sets. The area under the ROC curve of the 4-gene signature was highest among clinicopathological features in predicting OS and RFS. The 4-gene signature was found to be an independent prognostic indicator in USC and was a superior predictor of OS in early stage of USC. Conclusions: Our findings highlight the potential of the 4-gene signature as a guide for personalized USC treatment.

Gynecologic Cancer InterGroup (GCIG) Consensus Review for Uterine Serous Carcinoma

2014 ◽  
Vol 24 (Supp 3) ◽  
pp. S83-S89 ◽  
Author(s):  
Satoru Sagae ◽  
Nobuyuki Susumu ◽  
Akila N. Viswanathan ◽  
Daisuke Aoki ◽  
Floor J. Backes ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Gynecologic Cancer ◽  
Survival Rates ◽  
Serous Carcinoma ◽  
Molecular Characteristics ◽  
Histologic Subtype ◽  
High Propensity ◽  
Stage Disease ◽  
Uterine Serous Carcinoma

ObjectivesUterine serous carcinoma (USC) represents a rare and aggressive histologic subtype of endometrial cancer, associated with a poor prognosis. This article critically reviews the literature pertinent to the epidemiology, pathology, molecular biology, diagnosis, management, and perspectives of patients with USC.MethodsAs one of a series of The Gynecologic Cancer InterGroup (GCIG) Rare Tumor Working Group in London, November 2013, we discussed about USC many times with various experts among international GCIG groups.ResultsBoth USC and approximately 25% of high-grade endometrioid tumors represent extensive copy number alterations, few DNA methylation changes, low estrogen and progesterone levels, and frequent P53mutations. Uterine serous carcinoma shares molecular characteristics with ovarian serous and basal-like breast carcinomas. In addition to optimal surgery, platinum- and taxane-based chemotherapy should be considered in the treatment of both early- and advanced-stage disease. The combination of radiation and chemotherapy appears to be associated with the highest survival rates. The role of radiation therapy in the management of this disease, with a high propensity for distant failures, remains elusive.ConclusionsUterine serous carcinoma is a unique and biologically aggressive subtype of endometrial cancer and should be studied as a distinct entity. Futures studies should identify the optimized chemotherapy and radiation regimens, sequence of therapy and schedule, and the role of targeted biologic therapy.

scholarly journals Physical activity barriers and resources among black women with a history of breast and endometrial cancer: a systematic review

2020 ◽  
Vol 14 (4) ◽  
pp. 556-577
Author(s):  
Natasha R. Burse ◽  
Nishat Bhuiyan ◽  
Scherezade K. Mama ◽  
Kathryn H. Schmitz
Keyword(s):  
Physical Activity ◽  
Systematic Review ◽  
Endometrial Cancer ◽  
Black Women ◽  
History Of

scholarly journals History of uterine leiomyoma and risk of endometrial cancer in black women

2016 ◽  
Vol 27 (4) ◽  
pp. 545-552 ◽  
Author(s):  
Lauren A. Wise ◽  
Todd R. Sponholtz ◽  
Lynn Rosenberg ◽  
Lucile L. Adams-Campbell ◽  
Wendy Kuohung ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Black Women ◽  
Uterine Leiomyoma ◽  
History Of
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