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Journal of Clinical Oncology : Official... Jan 2018Leiomyosarcoma (LMS) is one of the most common subtypes of soft tissue sarcoma in adults and can occur in almost any part of the body. Uterine leiomyosarcoma is the most... (Review)
Review
Leiomyosarcoma (LMS) is one of the most common subtypes of soft tissue sarcoma in adults and can occur in almost any part of the body. Uterine leiomyosarcoma is the most common subtype of uterine sarcoma. Increased awareness of this unique histology has allowed for the development of drugs that are specific to LMS and has begun to shed light on the similarities and possible unique aspects of soft tissue and uterine LMS. In this review, we summarize the current understanding of the epidemiology, diagnosis, genomics, and treatment options for LMS.
Topics: Adult; Drug Development; Female; Genomics; Humans; Leiomyosarcoma; Sarcoma; Soft Tissue Neoplasms; Uterine Neoplasms
PubMed: 29220301
DOI: 10.1200/JCO.2017.75.9845 -
Gynecologic Oncology Jul 2021Serous endometrial cancer represents a relative rare entity accounting for about 10% of all diagnosed endometrial cancer, but it is responsible for 40% of endometrial... (Review)
Review
Serous endometrial cancer represents a relative rare entity accounting for about 10% of all diagnosed endometrial cancer, but it is responsible for 40% of endometrial cancer-related deaths. Patients with serous endometrial cancer are often diagnosed at earlier disease stage, but remain at higher risk of recurrence and poorer prognosis when compared stage-for-stage with endometrioid subtype endometrial cancer. Serous endometrial cancers are characterized by marked nuclear atypia and abnormal p53 staining in immunohistochemistry. The mainstay of treatment for newly diagnosed serous endometrial cancer includes a multi-modal therapy with surgery, chemotherapy and/or radiotherapy. Unfortunately, despite these efforts, survival outcomes still remain poor. Recently, The Cancer Genome Atlas (TCGA) Research Network classified all endometrial cancer types into four categories, of which, serous endometrial cancer mostly is found within the "copy number high" group. This group is characterized by the increased cell cycle deregulation (e.g., CCNE1, MYC, PPP2R1A, PIKCA, ERBB2 and CDKN2A) and TP53 mutations (90%). To date, the combination of pembrolizumab and lenvatinib is an effective treatment modality in second-line therapy, with a response rate of 50% in advanced/recurrent serous endometrial cancer. Owing to the unfavorable outcomes of serous endometrial cancer, clinical trials are a priority. At present, ongoing studies are testing novel combinations of various targeted and immunotherapeutic agents in newly diagnosed and advanced/recurrent endometrial cancer - an important strategy for serous endometrial cancer, whereby tumors are usually p53+ and pMMR, making response to PD-1 inhibitor monotherapy unlikely. Here, the rare tumor working group (including members from the European Society of Gynecologic Oncology (ESGO), Gynecologic Cancer Intergroup (GCIG), and Japanese Gynecologic Oncology Group (JGOG)), performed a narrative review reporting on the current landscape of serous endometrial cancer and focusing on standard and emerging therapeutic options for patients affected by this difficult disease.
Topics: Clinical Trials, Phase III as Topic; Cystadenocarcinoma, Serous; Female; Humans; Randomized Controlled Trials as Topic; Uterine Neoplasms
PubMed: 33934848
DOI: 10.1016/j.ygyno.2021.04.029 -
Journal of the National Cancer Institute Dec 2022Hair products may contain hazardous chemicals with endocrine-disrupting and carcinogenic properties. Previous studies have found hair product use to be associated with a...
BACKGROUND
Hair products may contain hazardous chemicals with endocrine-disrupting and carcinogenic properties. Previous studies have found hair product use to be associated with a higher risk of hormone-sensitive cancers including breast and ovarian cancer; however, to our knowledge, no previous study has investigated the relationship with uterine cancer.
METHODS
We examined associations between hair product use and incident uterine cancer among 33 947 Sister Study participants aged 35-74 years who had a uterus at enrollment (2003-2009). In baseline questionnaires, participants in this large, racially and ethnically diverse prospective cohort self-reported their use of hair products in the prior 12 months, including hair dyes; straighteners, relaxers, or pressing products; and permanents or body waves. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) to quantify associations between hair product use and uterine cancer using Cox proportional hazard models. All statistical tests were 2-sided.
RESULTS
Over an average of 10.9 years of follow-up, 378 uterine cancer cases were identified. Ever vs never use of straightening products in the previous 12 months was associated with higher incident uterine cancer rates (HR = 1.80, 95% CI = 1.12 to 2.88). The association was stronger when comparing frequent use (>4 times in the past 12 months) vs never use (HR = 2.55, 95% CI = 1.46 to 4.45; Ptrend = .002). Use of other hair products, including dyes and permanents or body waves, was not associated with incident uterine cancer.
CONCLUSION
These findings are the first epidemiologic evidence of association between use of straightening products and uterine cancer. More research is warranted to replicate our findings in other settings and to identify specific chemicals driving this observed association.
Topics: Female; Humans; Hair Preparations; Prospective Studies; Uterine Neoplasms; Proportional Hazards Models; Hair; Risk Factors; Breast Neoplasms
PubMed: 36245087
DOI: 10.1093/jnci/djac165 -
International Journal of Molecular... Aug 2022Uterine fibroids (UFs) are the most common benign tumors of female genital diseases, unlike uterine leiomyosarcoma (LMS), a rare and aggressive uterine cancer. This... (Review)
Review
Uterine fibroids (UFs) are the most common benign tumors of female genital diseases, unlike uterine leiomyosarcoma (LMS), a rare and aggressive uterine cancer. This narrative review aims to discuss the biology and diagnosis of LMS and, at the same time, their differential diagnosis, in order to distinguish the biological and molecular origins. The authors performed a Medline and PubMed search for the years 1990-2022 using a combination of keywords on the topics to highlight the many genes and proteins involved in the pathogenesis of LMS. The mutation of these genes, in addition to the altered expression and functions of their enzymes, are potentially biomarkers of uterine LMS. Thus, the use of this molecular and protein information could favor differential diagnosis and personalized therapy based on the molecular characteristics of LMS tissue, leading to timely diagnoses and potential better outcomes for patients.
Topics: Female; Humans; Leiomyoma; Leiomyosarcoma; Pelvic Neoplasms; Uterine Neoplasms; Uterus
PubMed: 36077127
DOI: 10.3390/ijms23179728 -
Seminars in Cancer Biology Apr 2020Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is an autosomal dominant hereditary cancer syndrome with incomplete penetrance. It is caused by a germline... (Review)
Review
Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is an autosomal dominant hereditary cancer syndrome with incomplete penetrance. It is caused by a germline amorphic allele of the FH gene, which encodes the TCA cycle enzyme, fumarate hydratase (FH). HLRCC patients are genetically predisposed to develop skin leiomyomas, uterine fibroids, and the aggressive kidney cancer of type 2 papillary morphology. Loss-of-heterozygocity at the FH locus that cause a complete loss of FH enzymatic function is always detected in these tumor tissues. Molecular pathway elucidation, genomic studies, and systematic genetics screens reported over the last two decades have identified several FH-inactivation driven pathways alterations, as well as rationally conceived treatment strategies that specifically target FH tumor cells. These treatment strategies include ferroptosis induction, oxidative stress promotion, and metabolic alteration. As the fundamental biology of HLRCC continues to be uncovered, these treatment strategies continue to be refined and may one day lead to a strategy to prevent disease onset among HLRCC patients. With a more complete picture of HLRCC biology, the safe translation of experimental treatment strategies into clinical practice is achievable in the foreseeable future.
Topics: Biomarkers, Tumor; Disease Management; Disease Susceptibility; Fumarate Hydratase; Genes, Tumor Suppressor; Genetic Predisposition to Disease; Genetic Testing; Genomics; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Leiomyomatosis; Mutation; Neoplastic Syndromes, Hereditary; Proteome; Signal Transduction; Skin Neoplasms; Translational Research, Biomedical; Uterine Neoplasms
PubMed: 31689495
DOI: 10.1016/j.semcancer.2019.10.016 -
International Journal of Gynaecology... Oct 2021Gestational trophoblastic disease (GTD) arises from abnormal placenta and is composed of a spectrum of premalignant to malignant disorders. Changes in epidemiology of...
Gestational trophoblastic disease (GTD) arises from abnormal placenta and is composed of a spectrum of premalignant to malignant disorders. Changes in epidemiology of GTD have been noted in various countries. In addition to histology, molecular genetic studies can help in the diagnostic pathway. Earlier detection of molar pregnancy by ultrasound has resulted in changes in clinical presentation and decreased morbidity from uterine evacuation. Follow-up with human chorionic gonadotropin (hCG) is essential for early diagnosis of gestational trophoblastic neoplasia (GTN). The duration of hCG monitoring varies depending on histological type and regression rate. Low-risk GTN (FIGO Stages I-III: score <7) is treated with single-agent chemotherapy but may require additional agents; although scores 5-6 are associated with more drug resistance, overall survival approaches 100%. High-risk GTN (FIGO Stages II-III: score ≥7 and Stage IV) is treated with multiagent chemotherapy, with or without adjuvant surgery for excision of resistant foci of disease or radiotherapy for brain metastases, achieving a survival rate of approximately 90%. Gentle induction chemotherapy helps reduce early deaths in patients with extensive tumor burden, but late mortality still occurs from recurrent treatment-resistant tumors.
Topics: Chorionic Gonadotropin; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Induction Chemotherapy; Neoplasm Recurrence, Local; Pregnancy; Uterine Neoplasms
PubMed: 34669197
DOI: 10.1002/ijgo.13877 -
Critical Reviews in Oncology/hematology Apr 2023Leiomyosarcoma (LMS) is a soft tissue sarcoma of smooth muscle origin that can arise in multiple anatomical sites and is broadly classified as extra-uterine LMS or... (Review)
Review
Leiomyosarcoma (LMS) is a soft tissue sarcoma of smooth muscle origin that can arise in multiple anatomical sites and is broadly classified as extra-uterine LMS or uterine LMS. There is substantial interpatient heterogeneity within this histological subtype, and despite multi-modal therapy, clinical management remains challenging with poor patient prognosis and few new therapies available. Here we discuss the current treatment landscape of LMS in both the localised and advanced disease setting. We further describe the latest advances in our evolving understanding of the genetics and biology of this group of heterogeneous diseases and summarise the key studies delineating the mechanisms of acquired and intrinsic chemotherapy resistance in this histological subtype. We conclude by providing a perspective on how novel targeted agents such as PARP inhibitors may usher in a new paradigm of biomarker-driven therapies that will ultimately impact the outcomes of patients with LMS.
Topics: Female; Humans; Leiomyosarcoma; Sarcoma; Antineoplastic Agents; Uterine Neoplasms; Biology
PubMed: 36893945
DOI: 10.1016/j.critrevonc.2023.103955 -
The Yale Journal of Biology and Medicine Jun 2015It has been known for more than 150 years that the risk of carcinoma of the uterine cervix correlates with the number of sexual partners. Laboratory and epidemiological... (Review)
Review
It has been known for more than 150 years that the risk of carcinoma of the uterine cervix correlates with the number of sexual partners. Laboratory and epidemiological evidence demonstrated that infection with certain human papillomavirus (HPV) types initiates the vast majority of, if not all, cervical cancer, as well as a substantial fraction of other cancers, including other anogenital cancer and oropharyngeal cancer. Pap smear testing resulted in a dramatic reduction in the incidence of cervical cancer in the developed world, and HPV vaccination has the potential to eradicate HPV-associated cancer worldwide and represents a major public health breakthrough. The major current challenge is to ensure that HPV vaccines are widely administered.
Topics: Female; Humans; Nuns; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines; Sexual Behavior; Uterine Neoplasms
PubMed: 26029011
DOI: No ID Found -
Obstetrics and Gynecology Apr 2022The Centers for Disease Control and Prevention recognized the need for educational materials for clinicians on the prevention and early diagnosis of gynecologic cancers.... (Review)
Review
The Centers for Disease Control and Prevention recognized the need for educational materials for clinicians on the prevention and early diagnosis of gynecologic cancers. The American College of Obstetricians and Gynecologists convened a panel of experts in evidence review from the Society for Academic Specialists in General Obstetrics and Gynecology and content experts from the Society of Gynecologic Oncology to review relevant literature, best practices, and existing practice guidelines as a first step toward developing evidence-based educational materials for women's health care clinicians about uterine cancer. Panel members conducted structured literature reviews, which were then reviewed by other panel members and discussed at a virtual meeting of stakeholder professional and patient advocacy organizations in January 2021. This article is the evidence summary of the relevant literature and existing recommendations to guide clinicians in the prevention, early diagnosis, and special considerations of uterine cancer. Substantive knowledge gaps are noted and summarized to provide guidance for future research.
Topics: Congresses as Topic; Female; Genital Neoplasms, Female; Gynecology; Humans; Obstetrics; Pregnancy; Uterine Neoplasms; Women's Health
PubMed: 35272316
DOI: 10.1097/AOG.0000000000004711 -
Histochemistry and Cell Biology Aug 2020Several risk factors like obesity and hyperlipidemia were described for endometrial cancer. Here, the nuclear NAD-dependent histone-deacetylase Sirtuin1 (SIRT1) seems to...
Several risk factors like obesity and hyperlipidemia were described for endometrial cancer. Here, the nuclear NAD-dependent histone-deacetylase Sirtuin1 (SIRT1) seems to be important. SIRT1 is also involved in cell regulatory mechanisms and can serve as tumor promotor or suppressor. Its role in tumor biology is not clear yet. In this study, we evaluated and correlated the SIRT1 expression with patients' tumor characteristics in endometrioid and clear-cell cancer of the uterus. 65 paraffin-embedded samples of patients with endometrial and clear-cell cancer of the uterus were immunohistochemically stained and SIRT1 expression was evaluated by immunoreactive score. The results were correlated to clinical and pathological tumor characteristics as well as to the expression of ARID1A and β-Catenin. The staining was significantly more intensive in uterine endometrioid carcinoma compared to uterine clear-cell carcinoma (p = 0.007). The expression of SIRT1 correlated significantly with the membranous expression of β-Catenin (p = 0.028) and ARID1A (p = 0.021). Patients with positive Sirtuin1 expression had a significantly better progression-free survival (p = 0.042), the overall survival showed a trend towards a better prognosis (p = 0.070). SIRT1 expression seems to be associated with improved progression-free survival in uterine cancer (endometrioid and clear-cell) and is correlated to the tumor suppressors β-Catenin and ARID1A. Further studies are necessary to elucidate the role of SIRT1 in uterine and ovarian cancer and its potential as a therapeutic target.
Topics: Adenocarcinoma, Clear Cell; Aged; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Sirtuin 1; Survival Analysis; Uterine Neoplasms
PubMed: 32388637
DOI: 10.1007/s00418-020-01873-x