Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 867
Filtrar
1.
Zhonghua Fu Chan Ke Za Zhi ; 54(12): 848-853, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31874475

RESUMO

Objective: To study influencing factors which cause the endometrial diseases in patients with breast cancer after operation. Methods: A retrospective study was performed on 212 breast cancer post-operation patients with endometrial diseases between June 2006 and January 2018 in Women's Hospital School of Medicine Zhejiang University to analyse the factors which influenced the endometrial diseases. Results: The abnormal uterine bleeding and endometrial thickness were related to the severity of endometrial disease in patients with breast cancer, and they were independent risk factors for breast cancer patients to have endometrial cancer (P<0.05) . When the diagnostic cut off value of endometrial thickness was ≥0.49 cm, the sensitivity and specificity to endometrial cancer were 78% and 25%, respectively. The average endometrial thickness was (0.56±0.39) cm in patients who were treated by selective estrogen receptor modulator (SERM) after gynecological surgery, which was significantly thicker than that of aromatase inhibitor (AI) group [ (0.33±0.23) cm] and no treatment group [ (0.44±0.28) cm, P<0.05]. The endometrial disease recurrent rate and reoperation rate in SERM group were (26.2%, 14.3%) slightly higher than that of AI group (9.5%, 4.8%) and no treatment group (21.6%, 4.9%), but there were not significant differences (all P>0.05). Conclusions: The clinical symptom of abnormal uterine bleeding and thickening endometrium are risk factors for breast cancer patients to have endometrial cancer. The endometrial thickness has high predictive value for breast cancer patients to diagnose endometrial cancer. The SERM treatment increases the endometrial thickness, recurrent rate and reoperation rate in post-operation patients.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Hiperplasia Endometrial/induzido quimicamente , Neoplasias do Endométrio/induzido quimicamente , Endométrio/efeitos dos fármacos , Moduladores de Receptor Estrogênico/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Hemorragia Uterina/etiologia , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Terapia Combinada , Hiperplasia Endometrial/epidemiologia , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/patologia , Endométrio/patologia , Moduladores de Receptor Estrogênico/uso terapêutico , Feminino , Humanos , Estudos Retrospectivos , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Índice de Gravidade de Doença , Ultrassonografia
2.
Niger J Clin Pract ; 22(1): 92-100, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30666026

RESUMO

Objectives: A prospective case-control study was carried out to assess the value of elastosonography in identifying endometrial pathology in women using Tamoxifen (TAM) for breast cancer. Materials and Methods: In total, 66 women using TAM for breast cancer were enrolled for the study with 61 premenopausal and 61 postmenopausal healthy controls. Ultrasonographic findings (strain ratio, endometrial thickness) were evaluated in regard to the duration of TAM usage, histopathological findings, and menopausal status. Results: Patients with endometrial cancer (EC) and cystic endometrial hyperplasia (CEH) were found to have longer duration of TAM usage, increased endometrial thickness, and higher strain ratios compared with controls. A significant positive correlation was found between duration of TAM usage, endometrial thickness, and the strain ratios. Endometrial thickness and the strain ratios were significant predictors for groups under risk. Cutoff values for endometrial thickness, strain ratios, and duration of TAM usage were 12.55 mm, 2.46, and 18 months in premenopausal group and 7.75 mm, 7.70, and 32 months in postmenopausal group to predict risky population, respectively. Conclusion: Endometrial tissue strain ratio was found to be significantly increased in cases with endometrial pathologies. Addition of elastosonography modality to B-mode may improve the diagnostic accuracy during the follow-up of women using TAM for breast cancer.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Técnicas de Imagem por Elasticidade/métodos , Hiperplasia Endometrial/diagnóstico por imagem , Neoplasias do Endométrio/diagnóstico por imagem , Endométrio/diagnóstico por imagem , Tamoxifeno/efeitos adversos , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Hiperplasia Endometrial/induzido quimicamente , Neoplasias do Endométrio/induzido quimicamente , Endométrio/efeitos dos fármacos , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Pré-Menopausa , Estudos Prospectivos , Tamoxifeno/uso terapêutico
3.
Environ Mol Mutagen ; 60(5): 395-403, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-29124779

RESUMO

In the Diethylstilbestrol [DES] Combined Cohort Follow-up, the age- and calendar-year specific standardized incidence ratio [SIR] for clear cell adenocarcinoma [CCA] was 27.6 (95% confidence interval [CI] 7.51-70.6) for the exposed women. The SIR for breast cancer was 1.17 (95% CI 1.01-1.36) and the hazard ratio [HR] adjusted for birth year and cohort for comparison with the unexposed was 1.05 (95% CI 0.79-1.41). The SIR for pancreatic cancer was 2.43 (95% CI 1.21-4.34) and the adjusted HR for comparison with unexposed women was 7.16 (95% CI 0.84-61.5). There was little evidence of excess risk for other sites. There appeared to be a deficit in risk for endometrial cancer among the exposed (SIR 0.61; 95% CI 0.35-0.98), and an excess in the unexposed (SIR 1.55; 95% CI 0.95-2.40); the adjusted HR was 0.45 (95% CI 0.22-0.93) for the internal comparison. There was no overall excess cancer risk in exposed women compared with general population rates (1.06; 95% CI 0.95-1.17) or with unexposed participants (adjusted HR 1.03; 95% CI 0.84-1.25). These data do not support the suggestion that there is a diathesis of cancers in DES exposed female offspring The excess risk of breast and pancreatic cancers that we observed is concerning and warrants continued follow-up and mechanistic investigation. Environ. Mol. Mutagen. 60:395-403, 2019. Published 2017. This article is a US Government work and is in the public domain in the USA.


Assuntos
Carcinógenos/toxicidade , Dietilestilbestrol/toxicidade , Exposição Materna , Troca Materno-Fetal/fisiologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Adenocarcinoma de Células Claras/induzido quimicamente , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/epidemiologia , Neoplasias do Endométrio/induzido quimicamente , Neoplasias do Endométrio/epidemiologia , Feminino , Humanos , Neoplasias Pancreáticas/induzido quimicamente , Neoplasias Pancreáticas/epidemiologia , Gravidez , Inquéritos e Questionários
4.
J Toxicol Sci ; 43(9): 557-563, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30185696

RESUMO

There is sometimes controversy over whether or not statistically significant responses produced in carcinogenicity studies have biologically significance. Ambiguous results from our previous two-year oral carcinogenicity study on acotiamide hydrochloride hydrate (acotiamide-HH), a prokinetic drug for functional dyspepsia, in rats made it unclear whether the drug may exhibit uterine carcinogenicity. To check this finding, we performed a second long-term carcinogenicity study using two identical control groups to more accurately evaluate uterine carcinogenesis by considering the incidence of spontaneous neoplasms. Female Fischer 344 rats were divided into three groups: the two control groups (control 1 and 2) were administered vehicle (0.5% w/v methylcellulose) and the acotiamide-HH-treated group was administered 2,000 mg/kg/day of acotiamide-HH by oral gavage for two years. Among all groups, the incidence of endometrial adenocarcinoma (EmA) was highest in the control 2 group, followed by the acotiamide-HH-treated group and the control 1 group. Moreover, acotiamide-HH did not affect the incidence of precursor lesions of EmA. In cases where an ambiguous difference is observed, the use of two control groups allows for a more informed interpretation of the findings in the drug-treated groups. The outcomes in this study strongly support the hypothesis that the increase in EmA in rats treated with acotiamide-HH in our previous study is unrelated to administration of the drug.


Assuntos
Adenocarcinoma/induzido quimicamente , Benzamidas/toxicidade , Testes de Carcinogenicidade/métodos , Grupos Controle , Neoplasias do Endométrio/induzido quimicamente , Tiazóis/toxicidade , Administração Oral , Animais , Benzamidas/administração & dosagem , Reações Falso-Positivas , Feminino , Ratos Endogâmicos F344 , Tiazóis/administração & dosagem , Fatores de Tempo
5.
Cancer Sci ; 109(10): 3316-3325, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30063274

RESUMO

A meta-analysis published in 2015 noted a marginally increased risk of endometrial and ovarian cancers in non-smoking women with dietary acrylamide intake, but only a few studies were included, and they were limited to Western countries. The aim of this study was to investigate the association between dietary acrylamide intake and endometrial or ovarian cancer risk in the Japan Public Health Center-based Prospective Study (JPHC Study). In this prospective cohort study, 47 185 participants aged 45-74 years at the follow-up starting point in the JPHC Study were enrolled. Dietary acrylamide intake was assessed using a validated food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI). In participants with endometrial and ovarian cancer, the average follow-up periods were 15.5 and 15.6 years, respectively, and 161 and 122 cases of endometrial and ovarian cancer were diagnosed, respectively. Energy-adjusted dietary acrylamide intake was negatively associated with endometrial cancer, but the association disappeared after adjusting for coffee consumption with an adjusted HR for the highest vs lowest tertile of 0.85 (95%CI: 0.54-1.33). No association was observed, however, for ovarian cancer (adjusted HR, 0.77; 95%CI: 0.49-1.23). Furthermore, after stratifying by smoking status, coffee consumption, alcohol consumption, body mass index, and menopause status, no association was observed. Dietary acrylamide intake was not associated with the risk of endometrial or ovarian cancer in Japanese women with a relatively lower dietary intake of acrylamide compared with Western populations.


Assuntos
Acrilamida/toxicidade , Inquéritos sobre Dietas/estatística & dados numéricos , Neoplasias do Endométrio/epidemiologia , Neoplasias Ovarianas/epidemiologia , Idoso , Índice de Massa Corporal , Café , Neoplasias do Endométrio/induzido quimicamente , Comportamento Alimentar , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/induzido quimicamente , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
6.
Toxicol Pathol ; 46(5): 574-596, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29895210

RESUMO

Developmental exposure to estrogenic chemicals is an established risk factor for cancer of the female reproductive tract. This increase in risk has been associated with disruption of normal patterns of cellular differentiation during critical stages of morphogenesis. The goal of this study was to document uterine epithelial phenotypes over time following neonatal treatment with the synthetic estrogen diethylstilbestrol (DES) or the soy phytoestrogen genistein (GEN) in female CD-1 mice. Both DES and GEN induced three distinct populations of abnormal endometrial epithelial cells: luminal (SIX1+/P63-/CK14-/CK18+), basal (SIX1+/P63+/CK14+/CK18-), and mixed/bipotential (SIX1+/P63-/CK14+/CK18+), which were all established by early adulthood. In older animals, DES and GEN resulted in uterine carcinomas with mixed glandular, basal, and squamous cell elements. All carcinomas were composed largely of the three abnormal cell types. These findings identify novel epithelial differentiation patterns in the uterus and support the idea that disruption of cellular programming in early development can influence cancer risk later in life.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Neoplasias do Endométrio/induzido quimicamente , Endométrio/efeitos dos fármacos , Estrogênios/toxicidade , Morfogênese/efeitos dos fármacos , Lesões Pré-Cancerosas/induzido quimicamente , Animais , Animais Recém-Nascidos , Dietilestilbestrol/toxicidade , Neoplasias do Endométrio/patologia , Endométrio/crescimento & desenvolvimento , Endométrio/patologia , Feminino , Genisteína/toxicidade , Imuno-Histoquímica , Camundongos Endogâmicos , Lesões Pré-Cancerosas/patologia
7.
Cochrane Database Syst Rev ; 5: CD008830, 2018 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-29763969

RESUMO

BACKGROUND: Endometrial cancer is the sixth most common cancer in women worldwide and most commonly occurs after the menopause (75%) (globocan.iarc.fr). About 319,000 new cases were diagnosed worldwide in 2012. Endometrial cancer is commonly considered as a potentially 'curable cancer,' as approximately 75% of cases are diagnosed before disease has spread outside the uterus (FIGO (International Federation of Gynecology and Obstetrics) stage I). The overall five-year survival for all stages is about 86%, and, if the cancer is confined to the uterus, the five-year survival rate may increase to 97%. The majority of women diagnosed with endometrial cancer have early-stage disease, leading to a good prognosis after hysterectomy and removal of the ovaries (oophorectomy), with or without radiotherapy. However, women may have early physiological and psychological postmenopausal changes, either pre-existing or as a result of oophorectomy, depending on age and menopausal status at the time of diagnosis. Lack of oestrogen can cause hot flushes, night sweats, genital tract atrophy and longer-term adverse effects, such as osteoporosis and cardiovascular disease. These changes may be temporarily managed by using oestrogens, in the form of hormone replacement therapy (HRT). However, there is a theoretical risk of promoting residual tumour cell growth and increasing cancer recurrence. Therefore, this is a potential survival disadvantage in a woman who has a potentially curable cancer. In premenopausal women with endometrial cancer, treatment induces early menopause and this may adversely affect overall survival. Additionally, most women with early-stage disease will be cured of their cancer, making longer-term quality of life (QoL) issues more pertinent. Following bilateral oophorectomy, premenopausal women may develop significant and debilitating menopausal symptoms, so there is a need for information about the risk and benefits of taking HRT, enabling women to make an informed decision, weighing the advantages and disadvantages of using HRT for their individual circumstances. OBJECTIVES: To assess the risks and benefits of HRT (oestrogen alone or oestrogen with progestogen) for women previously treated for endometrial cancer. SEARCH METHODS: We searched the Cochrane Register of Controlled Trials (CENTRAL 2017, Issue 5), MEDLINE (1946 to April, week 4, 2017) and Embase (1980 to 2017, week 18). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of review articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs), in all languages, that examined the efficacy of symptom relief and the safety of using HRT in women treated for endometrial cancer, where safety in this situation was considered as not increasing the risk of recurrence of endometrial cancer above that of women not taking HRT. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified 2190 unique records, evaluated the full text of seven studies and included one study with 1236 participants. This study reported tumour recurrence in 2.3% of women in the oestrogen arm versus 1.9% of women receiving placebo (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.54 to 2.50; very low-certainty evidence). The study reported one woman in the HRT arm (0.16%) and three women in the placebo arm (0.49%) who developed breast cancer (new malignancy) during follow-up (RR 0.80, 95% CI 0.32 to 2.01; 1236 participants, 1 study; very low-certainty evidence). The study did not report on symptom relief, overall survival or progression-free survival for HRT versus placebo. However, they did report the percentage of women alive with no evidence of disease (94.3% in the HRT group and 95.6% in the placebo group) and the percentage of women alive irrespective of disease progression (95.8% in the HRT group and 96.9% in the placebo group) at the end of the 36 months' follow-up. The study did not report time to recurrence and it was underpowered due to closing early. The authors closed it as a result of the publication of the Women's Health Initiative (WHI) study, which, at that time, suggested that risks of exogenous hormone therapy outweighed benefits and had an impact on study recruitment. No assessment of efficacy was reported. AUTHORS' CONCLUSIONS: Currently, there is insufficient high-quality evidence to inform women considering HRT after treatment for endometrial cancer. The available evidence (both the single RCT and non-randomised evidence) does not suggest significant harm, if HRT is used after surgical treatment for early-stage endometrial cancer. There is no information available regarding use of HRT in higher-stage endometrial cancer (FIGO stage II and above). The use of HRT after endometrial cancer treatment should be individualised, taking account of the woman's symptoms and preferences, and the uncertainty of evidence for and against HRT use.


Assuntos
Neoplasias do Endométrio/induzido quimicamente , Terapia de Reposição de Estrogênios/efeitos adversos , Recidiva Local de Neoplasia/induzido quimicamente , Neoplasias da Mama/epidemiologia , Término Precoce de Ensaios Clínicos , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Recidiva Local de Neoplasia/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Qualidade de Vida
8.
J Obstet Gynaecol Res ; 44(6): 1140-1149, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29516573

RESUMO

AIM: The purpose of this study was to determine the prognostic factors and patterns of failure in lymphovascular space invasion (LVSI)-positive women with stage IIIC endometrioid endometrial cancer (EC). METHODS: A multicenter, retrospective, department database review was performed to identify LVSI-positive patients with stage IIIC endometrioid EC at five gynecological oncology centers in Turkey. Demographic, clinicopathological and survival data were collected. RESULTS: We identified 172 LVSI-positive women with stage IIIC endometrioid EC during the study period; 75 (43.6%) were classified as Stage IIIC1 and 97 (56.4%) as Stage IIIC2 . The median age at diagnosis was 59 years, and the median duration of follow up was 34.5 months. The total number of recurrences was 46 (26.7%). We observed 14 (8.1%) locoregional recurrences, 12 (7.0%) retroperitoneal failures and 20 (11.6%) distant relapses. For the entire study cohort, 5-year progression-free survival (PFS) was 67.4%, while the 5-year overall survival (OS) rate was 75.1%. Grade 3 histology (hazard ratio [HR] 2.62, 95% confidence interval [CI] 1.34-5.12; P = 0.005), cervical stromal invasion (HR 2.33, 95% CI 1.09-4.99; P = 0.028) and myometrial invasion (MMI) ≥50% (HR 4.0, 95% CI 1.16-13.69; P = 0.028) were found to be independent prognostic factors for decreased OS. CONCLUSION: Uterine factors such as grade 3 disease, cervical stromal invasion and deep MMI seem to be independently associated with decreased OS in LVSI-positive women with stage IIIC endometrioid EC. The high distant recurrence rate in this subgroup of patients warrants further studies in order to identify the most effective treatment strategy for those patients.


Assuntos
Carcinoma Endometrioide , Neoplasias do Endométrio , Vasos Linfáticos/patologia , Recidiva Local de Neoplasia , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/epidemiologia , Carcinoma Endometrioide/patologia , Intervalo Livre de Doença , Neoplasias do Endométrio/induzido quimicamente , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Turquia/epidemiologia
9.
Climacteric ; 21(4): 321-325, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29583028

RESUMO

It is well established that unopposed estrogen for hormone therapy in postmenopausal women (MHT) induces a dose-related stimulation of the endometrium associated with an increased risk of hyperplasia and endometrial cancer. Progesterone acts physiologically to counteract the proliferative effects of estradiol during the menstrual cycle. In MHT, progestogens protect the endometrium against the proliferative effects of estrogens in women with a uterus. Recent data suggest that, whereas micronized progesterone is apparently safer for the breast, it could be less efficient than synthetic progestin on the endometrium. An update on progestogen and endometrial safety in MHT is the subject of this review.


Assuntos
Mama/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Terapia de Reposição de Estrogênios/métodos , Progesterona/fisiologia , Progestinas/fisiologia , Neoplasias da Mama/induzido quimicamente , Neoplasias do Endométrio/induzido quimicamente , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Humanos , Perimenopausa , Progesterona/efeitos adversos , Progestinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Cell Physiol Biochem ; 44(6): 2357-2367, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29262396

RESUMO

BACKGROUND/AIMS: Benzotriazole (BTR) and its derivatives, such as intermediates and UV stabilizers, are important man-made organic chemicals found in everyday life that have been recently identified as environmental toxins and a threat to female reproductive health. Previous studies have shown that BTR could act as a carcinogen by mimicking estrogen. Environmental estrogen mimics could promote the initiation and development of female cancers, such as endometrial carcinoma, a type of estrogenic-sensitive malignancy. However, there is little information on the relationship between BTR and endometrial carcinoma. In this study, we aimed to demonstrate the biological function of BTR in endometrial carcinoma and explored the underlying mechanism. METHODS: The CCK-8 assay was performed to detect cell viability; transwell-filter assay was used to assess cell invasion; gene microarray analysis was employed to determine gene expression patterns in response to BTR treatment; western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were carried out to detect the expression levels of BTR-related genes. RESULTS: Our data showed that BTR could induce the invasion and migration of endometrial carcinoma cells (Ishikawa and HEC-1-B). In addition, BTR increased the expression level of CTBP1, which could enhance the epithelial-mesenchymal transition (EMT) in cancer cells. Moreover, CTBP1 silencing reversed the effect of BTR on EMT progression in endometrial carcinoma cells. CONCLUSION: This study indicates that BTR could act as a carcinogen to promote the development of endometrial carcinoma mainly through CTBP1-mediated EMT, which deserves more attention.


Assuntos
Carcinógenos Ambientais/efeitos adversos , Neoplasias do Endométrio/induzido quimicamente , Neoplasias do Endométrio/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Triazóis/efeitos adversos , Oxirredutases do Álcool/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Neoplasias do Endométrio/genética , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia
12.
Eur J Cancer ; 84: 60-68, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28783542

RESUMO

AIM: We aimed to assess the overall cancer risk among contemporary menopausal hormone therapy (MHT) users in Sweden and the risk for different cancer types. METHODS: A nationwide Swedish population-based cohort study including all 290,186 women aged ≥ 40 years having used systemic MHT during the study period (July 2005 and December 2012), compared with the Swedish female background population. MHT ever-use (all MHT, oestrogen-only MHT [E-MHT] and oestrogen plus progestin MHT [EP-MHT]) was based on the nationwide Prescribed Drug Registry. Cancer diagnoses were grouped into 16 different anatomical locations, for which standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated. RESULTS: The SIR of any cancer was 1.09 (95% CI: 1.07-1.11) following ever MHT, 1.04 (95% CI: 1.01-1.06) for E-MHT and 1.14 (95% CI: 1.12-1.17) for EP-MHT. The highest SIR was found for EP-MHT among users aged ≥70 years (SIR = 1.33, 95% CI: 1.26-1.40). The risk for invasive breast, endometrial or ovarian cancer combined was increased for any MHT (SIR = 1.31, 95% CI: 1.28-1.34). The risk of invasive breast cancer was increased following MHT and increased with age for EP-MHT users. The risk of gastrointestinal cancers combined was decreased (SIR = 0.90, 95% CI: 0.86-0.94), particularly the oesophagus (SIR = 0.81, 95% CI: 0.64-1.00), liver (SIR = 0.81, 95% CI: 0.65-0.99) and colon (SIR = 0.90, 95% CI: 0.84-0.95). CONCLUSIONS: MHT, notably EP-MHT, was associated with a limited increase in overall cancer risk. The increased risk of female reproductive organ cancers was almost balanced by a decreased risk of gastrointestinal cancers.


Assuntos
Terapia de Reposição de Estrogênios/efeitos adversos , Estrogênios/efeitos adversos , Menopausa , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Progestinas/efeitos adversos , Adulto , Idoso , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/epidemiologia , Neoplasias do Sistema Digestório/epidemiologia , Neoplasias do Sistema Digestório/prevenção & controle , Esquema de Medicação , Composição de Medicamentos , Neoplasias do Endométrio/induzido quimicamente , Neoplasias do Endométrio/epidemiologia , Estrogênios/administração & dosagem , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/prevenção & controle , Neoplasias Ovarianas/induzido quimicamente , Neoplasias Ovarianas/epidemiologia , Progestinas/administração & dosagem , Fatores de Proteção , Sistema de Registros , Medição de Risco , Fatores de Risco , Suécia/epidemiologia , Fatores de Tempo
13.
Toxicol Lett ; 279 Suppl 1: 75-97, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-28676441

RESUMO

Octamethylcyclotetrasiloxane (D4) is a cyclic volatile methylsiloxane primarily used in the synthesis of silicon-based materials used in a variety of consumer products. This paper details the chronic toxicity and oncogenicity evaluation of D4 in the Fischer 344 rat. Animals were exposed to 0, 10, 30, 150, or 700ppm D4 vapor for 6h/day, 5days/week for up to 104 weeks in whole-body inhalation chambers. Effects of two year chronic exposure included increased liver, kidney, testes, and uterine weight with correlating microscopic findings of hepatocellular hypertrophy (males only), chronic nephropathy (both sexes), interstitial cell hyperplasia, and cystic endometrial hyperplasia and endometrial adenoma, respectively. Upper respiratory tract irritation and lymphocytic leukocytosis were evident in both sexes. Increased neoplasia was demonstrated only in the uterus. Uterine endometrial adenomas were present in four of sixty animals exposed to 700ppm D4 for 24 months. None were present in the other treatment groups. In contrast, in 700ppm D4 group males the incidence of pituitary and pancreatic neoplasia was reduced as was thyroid c-cell adenoma/carcinoma in 700ppm females. This study has identified that D4 is a mild respiratory irritant and increases liver and kidney weight without inducing neoplasia in these tissues. The increased incidence of uterine adenoma was the only treatment-related neoplastic finding associated with chronic exposure to D4.


Assuntos
Adenoma/induzido quimicamente , Doença Hepática Induzida por Substâncias e Drogas/patologia , Neoplasias do Endométrio/induzido quimicamente , Nefropatias/induzido quimicamente , Siloxanas/toxicidade , Tecido Adiposo Marrom/química , Tecido Adiposo Marrom/metabolismo , Administração por Inalação , Animais , Relação Dose-Resposta a Droga , Poluentes Ambientais/administração & dosagem , Poluentes Ambientais/química , Poluentes Ambientais/metabolismo , Poluentes Ambientais/toxicidade , Feminino , Nefropatias/patologia , Masculino , Estrutura Molecular , Distribuição Aleatória , Ratos , Ratos Endogâmicos F344 , Siloxanas/administração & dosagem , Siloxanas/química , Siloxanas/metabolismo
14.
PLoS One ; 12(7): e0179360, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28742092

RESUMO

Estrogen-mimicking chemicals, such as cadmium, may be associated with increased susceptibility to hormone-dependent cancers, though supporting data are sparse, particularly for endometrial cancer. The Health and Environmental Exposure Research (HEER) study worked with the Arkansas Central Cancer Registry, Iowa Cancer Registry and Missouri Cancer Registry to obtain names of women diagnosed with endometrial cancer who were willing to be contacted for participation in our case control study. Voter registration lists from Iowa and Missouri were used to randomly select similarly aged women as represented in the case population. Participants were interviewed by telephone to obtain information on known or suspected endometrial risk factors. Urine kits were sent to participants for home collection and returned for analysis. Our case-control study consisted of 631 incident cases of endometrial cancer diagnosed from January 2010 to October 2012 and 879 age-matched population-based controls, ages 18-81 years (mean age 65 years). We quantified cadmium amounts in urine and standardized these values through creatinine adjustment. Using data from all survey completers, we developed a multivariable model for endometrial cancer. Creatinine-adjusted cadmium concentration was added to this model. Odds ratio (OR) and 95% confidence intervals (CIs) for endometrial cancer were calculated. After multivariable adjustment, higher creatinine-adjusted cadmium exposure was associated with a statistically significant increase of endometrial cancer risk (OR: 1.22; 95% CI: 1.03-1.44). Our results provide evidence that cadmium may increase the risk of endometrial cancer, possibly through estrogenic effects.


Assuntos
Cádmio/toxicidade , Neoplasias do Endométrio/induzido quimicamente , Neoplasias do Endométrio/epidemiologia , Exposição Ambiental/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cádmio/urina , Estudos de Casos e Controles , Intervalos de Confiança , Neoplasias do Endométrio/urina , Poluentes Ambientais/toxicidade , Poluentes Ambientais/urina , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Sistema de Registros , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
15.
Cancer Invest ; 35(5): 313-324, 2017 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-28402678

RESUMO

Tamoxifen treatment in breast cancer patients is associated with increased risk of endometrial malignancies. Significantly, higher AGR2 expression was found in endometrial cancers that developed in women previously treated with tamoxifen compared to those who had not been exposed to tamoxifen. An association of elevated AGR2 level with myometrial invasion occurrence and invasion depth was also found. In vitro analyses identified a stimulatory effect of AGR2 on cellular proliferation. Although adverse tamoxifen effects on endometrial cells remain elusive, our work identifies elevated AGR2 as a candidate tamoxifen-dependent mechanism of action responsible for increased incidence of endometrial cancer.


Assuntos
Adenocarcinoma/induzido quimicamente , Adenocarcinoma/metabolismo , Antineoplásicos Hormonais/toxicidade , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/induzido quimicamente , Neoplasias do Endométrio/induzido quimicamente , Endométrio/efeitos dos fármacos , Proteínas/metabolismo , Tamoxifeno/toxicidade , Células A549 , Adenocarcinoma/genética , Adenocarcinoma/patologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Endométrio/metabolismo , Endométrio/patologia , Feminino , Humanos , Células MCF-7 , Invasividade Neoplásica , Proteínas/genética , Interferência de RNA , Estudos Retrospectivos , Fatores de Risco , Transdução de Sinais/efeitos dos fármacos , Transfecção , Regulação para Cima
16.
Sci Rep ; 7: 43940, 2017 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-28266626

RESUMO

Tamoxifen is administered for estrogen receptor positive (ER+) breast cancers, but it can induce uterine endometrial cancer and non-alcoholic fatty liver disease (NAFLD). Importantly, ten years of tamoxifen treatment has greater protective effect against ER+ breast cancer than five years of such treatment. Tamoxifen was also approved by the FDA as a chemopreventive agent for those deemed at high risk for the development of breast cancer. The side effects are of substantial concern because of these extended methods of tamoxifen administration. In this study, we found that anordrin, marketed as an antifertility medicine in China, inhibited tamoxifen-induced endometrial epithelial cell mitosis and NAFLD in mouse uterus and liver as an anti-estrogenic and estrogenic agent, respectively. Additionally, compared with tamoxifen, anordiol, the active metabolite of anordrin, weakly bound to the ligand binding domain of ER-α. Anordrin did not regulate the classic estrogen nuclear pathway; thus, it did not affect the anti-tumor activity of tamoxifen in nude mice. Taken together, these data suggested that anordrin could eliminate the side effects of tamoxifen without affecting its anti-tumor activity.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Anticoncepcionais Orais Sintéticos/administração & dosagem , Neoplasias do Endométrio/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Norandrostanos/administração & dosagem , Tamoxifeno/efeitos adversos , Animais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/farmacologia , Linhagem Celular Tumoral , Neoplasias do Endométrio/induzido quimicamente , Feminino , Xenoenxertos , Humanos , Camundongos Endogâmicos ICR , Camundongos Nus , Transplante de Neoplasias , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Tamoxifeno/administração & dosagem , Tamoxifeno/farmacologia , Resultado do Tratamento
17.
Cochrane Database Syst Rev ; 3: CD010931, 2017 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-28349511

RESUMO

BACKGROUND: Medical treatment for subfertility principally involves the use of ovary-stimulating agents, including selective oestrogen receptor modulators (SERMs), such as clomiphene citrate, gonadotropins, gonadotropin-releasing hormone (GnRH) agonists and antagonists, as well as human chorionic gonadotropin. Ovary-stimulating drugs may act directly or indirectly upon the endometrium (lining of the womb). Nulliparity and some causes of subfertility are recognized as risk factors for endometrial cancer. OBJECTIVES: To evaluate the association between the use of ovary-stimulating drugs for the treatment of subfertility and the risk of endometrial cancer. SEARCH METHODS: A search was performed in CENTRAL, MEDLINE (Ovid) and Embase (Ovid) databases up to July 2016, using a predefined search algorithm. A search in OpenGrey, ProQuest, ClinicalTrials.gov, ZETOC and reports of major conferences was also performed. We did not impose language and publication status restrictions. SELECTION CRITERIA: Cohort and case-control studies reporting on the association between endometrial cancer and exposure to ovary-stimulating drugs for subfertility in adult women were deemed eligible. DATA COLLECTION AND ANALYSIS: Study characteristics and findings were extracted by review authors independently working in pairs. Inconsistency between studies was quantified by estimating I2. Random-effects (RE) models were used to calculate pooled effect estimates. Separate analyses were performed, comparing treated subfertile women versus general population and/or unexposed subfertile women, to address the superimposition of subfertility as an independent risk factor for endometrial cancer. MAIN RESULTS: Nineteen studies were eligible for inclusion (1,937,880 participants). Overall, the quality of evidence was very low, due to serious risk of bias and indirectness (non-randomised studies (NRS), which was reflected on the GRADE assessment.Six eligible studies, including subfertile women, without a general population control group, found that exposure to any ovary-stimulating drug was not associated with an increased risk of endometrial cancer (RR 0.96, 95% CI 0.67 to 1.37; 156,774 participants; very low quality evidence). Fifteen eligible studies, using a general population as the control group, found an increased risk after exposure to any ovary-stimulating drug (RR 1.75, 95% CI 1.18 to 2.61; 1,762,829 participants; very low quality evidence).Five eligible studies, confined to subfertile women (92,849 participants), reported on exposure to clomiphene citrate; the pooled studies indicated a positive association ( RR 1.32; 95% CI 1.01 to 1.71; 88,618 participants; very low quality evidence), although only at high dosage (RR 1.69, 95% CI 1.07 to 2.68; two studies; 12,073 participants) and at a high number of cycles (RR 1.69, 95% CI 1.16 to 2.47; three studies; 13,757 participants). Four studies found an increased risk of endometrial cancer in subfertile women who required clomiphene citrate compared to a general population control group (RR 1.87, 95% CI 1.00 to 3.48; four studies, 19,614 participants; very low quality evidence). These data do not tell us whether the association is due to the underlying conditions requiring clomiphene or the treatment itself.Using unexposed subfertile women as controls, exposure to gonadotropins was associated with an increased risk of endometrial cancer (RR 1.55, 95% CI 1.03 to 2.34; four studies; 17,769 participants; very low quality evidence). The respective analysis of two studies (1595 participants) versus the general population found no difference in risk (RR 2.12, 95% CI 0.79 to 5.64: very low quality evidence).Exposure to a combination of clomiphene citrate and gonadotropins, compared to unexposed subfertile women, produced no difference in risk of endometrial cancer (RR 1.18, 95% CI 0.57 to 2.44; two studies; 6345 participants; very low quality evidence). However, when compared to the general population, an increased risk was found , suggesting that the key factor might be subfertility, rather than treatment (RR 2.99, 95% CI 1.53 to 5.86; three studies; 7789 participants; very low quality evidence). AUTHORS' CONCLUSIONS: The synthesis of the currently available evidence does not allow us to draw robust conclusions, due to the very low quality of evidence. It seems that exposure to clomiphene citrate as an ovary-stimulating drug in subfertile women is associated with increased risk of endometrial cancer, especially at doses greater than 2000 mg and high (more than 7) number of cycles. This may largely be due to underlying risk factors in women who need treatment with clomiphene citrate, such as polycystic ovary syndrome, rather than exposure to the drug itself. The evidence regarding exposure to gonadotropins was inconclusive.


Assuntos
Clomifeno/efeitos adversos , Neoplasias do Endométrio/induzido quimicamente , Fármacos para a Fertilidade Feminina/efeitos adversos , Gonadotropinas/efeitos adversos , Infertilidade Feminina/tratamento farmacológico , Estudos de Casos e Controles , Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/efeitos adversos , Clomifeno/administração & dosagem , Quimioterapia Combinada/efeitos adversos , Neoplasias do Endométrio/epidemiologia , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/efeitos adversos , Humanos , Infertilidade Feminina/complicações , Indução da Ovulação , Estudos Retrospectivos , Risco
18.
J Clin Psychiatry ; 78(6): 714-719, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28199787

RESUMO

BACKGROUND: The use of antipsychotics may increase the risk of endometrial cancer through elevation of prolactin levels. We investigated the association between antipsychotics that are known to cause prolactin elevation and the risk of endometrial cancer. METHODS: In data from the United Kingdom Clinical Practice Research Datalink, all women who were newly treated with antipsychotics from 1990-2013 were identified and followed until 2014. Within this cohort of antipsychotic users, a nested case-control analysis was conducted. Main exposure was nonsporadic use of prolactin-elevating antipsychotics, and the active comparator was prolactin-sparing antipsychotics. Cases were women newly diagnosed with endometrial cancer (ICD-10) matched with up to 20 controls on age, calendar year of cohort entry, linkability to the Hospital Episode Statistics repository, and duration of follow-up. Conditional logistic regression models were used to determine the association of prolactin-elevating antipsychotics and endometrial cancer compared with prolactin-sparing antipsychotics. All analyses were adjusted for relevant potential confounders, including smoking, obesity, and diabetes mellitus. RESULTS: The cohort included 65,930 women. During 366,112 person-years of follow-up, there were 139 cases of endometrial cancer (incidence rate: 38/100,000 person-years), which were matched to 1,603 controls. Compared with the use of prolactin-sparing antipsychotics, the use of prolactin-elevating antipsychotics was not associated with an increased risk of endometrial cancer (adjusted odds ratio [aOR] = 1.00; 95% CI, 0.68-1.48). These findings remained similar with different durations of use (≤ 1 year, aOR = 1.07; 95% CI, 0.64-1.78, and > 1 year, aOR = 0.95; 95% CI, 0.58-1.54) and were robust to various sensitivity analyses. CONCLUSIONS: Prolactin-elevating antipsychotics were not associated with an increased risk of endometrial cancer.


Assuntos
Antipsicóticos/efeitos adversos , Neoplasias do Endométrio/induzido quimicamente , Transtornos Mentais/tratamento farmacológico , Prolactina/efeitos dos fármacos , Idoso , Estudos de Casos e Controles , Neoplasias do Endométrio/epidemiologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Reino Unido/epidemiologia
19.
Toxicol Lett ; 279 Suppl 1: 42-53, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-28109826

RESUMO

Octamethylcyclotetrasiloxane (D4) is a cyclic siloxane primarily used as a monomer or intermediate in the production of silicone polymers resulting in potential exposure of workers, and potential low level inhalation or dermal exposure for consumers and the general public. Following a two-year inhalation toxicity study with D4 in rats, increases in uterine endometrial cystic hyperplasia and adenomas were observed at the highest concentration of D4 administered (700ppm). No other neoplasms were increased with D4 treatment. In addition, chronic inhalation exposure of rats to D4 induced changes in relative liver and kidney weights, and produced a chronic nephropathy. This manuscript examines the biological relevance and possible modes of action for the effects observed in the F344 rat following chronic inhalation exposure to D4. D4 is not genotoxic and appears to exert its effects through a nongenotoxic mode of action. An alteration in the estrous cycle in the aging F344 rat was the most likely mode of action for the observed uterine effects following chronic inhalation exposure. Data support the conclusion that D4 acts indirectly via a dopamine-like mechanism leading to alteration of the pituitary control of the estrous cycle in aging F344 rats with a decrease in progesterone and an increase in the estrogen/progesterone ratio most likely induced by a decrease in prolactin concentration. D4 also inhibited the pre-ovulatory LH surge causing a delay in ovulation, persistent follicles and thus a prolonged exposure to elevated estrogen in the adult Sprague Dawely rat. A lengthening of the estrous cycle in the F344 rat with an increase in endogenous estrogen was also induced by D4 inhalation. Although the mode of action responsible for induction of uterine adenomas in the female F344 rat has not been clearly confirmed, the subtlety of effects on the effects of D4 on cyclicity may prevent further assessment and definition of the mode of action. The occurrence of uterine endometrial adenoma in the rat is not relevant for human risk characterization because (1) there are differences in ovulatory cycle regulation in rats compared to humans, (2) cystic hyperplasia without atypia in women is not a cancer precursor, and (3) there is no endometrial lesion in women that is directly analogous to endometrial adenoma in the rat. The effects of D4 on liver are due to a phenobarbital-like mechanism that results in induction of cytochrome P450 and other enzymes of xenobiotic biotransformation. The liver effects are adaptive and not adverse. Kidney findings included chonic progressive nephropathy, a rat lesion that has no counterpart in the human and that should not be used in human risk assessment.


Assuntos
Neoplasias do Endométrio/induzido quimicamente , Fígado/efeitos dos fármacos , Siloxanas/toxicidade , Administração por Inalação , Animais , Esquema de Medicação , Ciclo Estral/efeitos dos fármacos , Feminino , Fígado/anatomia & histologia , Tamanho do Órgão , Ratos , Ratos Endogâmicos F344 , Siloxanas/administração & dosagem , Siloxanas/química , Siloxanas/farmacocinética
20.
Eur J Cancer Prev ; 26(3): 225-231, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27222938

RESUMO

Metformin may reduce the risk of endometrial cancer whereas other drugs for the treatment of type 2 diabetes mellitus appear to increase it, although the evidence is still limited. We investigated this issue using data from a nested case-control study within the healthcare utilization databases of the Lombardy Region, Italy. This study included 376 diabetic women with endometrial cancer and 7485 diabetic controls matched for cases on age, date at cohort entry, and duration of follow-up. We used conditional logistic regression models to estimate the odds ratio (OR) of endometrial cancer in relation to use of antidiabetic drugs, adjusted for the Charlson's comorbidity index, selected medical conditions, prescription of selected drugs, and concomitant use of other antidiabetic drugs. At cohort entry, no significant associations were observed for metformin [OR=0.99, 95% confidence interval (CI) 0.80-1.23], sulfonylureas (OR=1.14, 95% CI 0.91-1.42), insulin (OR=0.72, 95% CI 0.34-1.56), and other antidiabetic drugs (OR=1.21, 95% CI 0.75-1.95). When we considered use during follow-up, a borderline significant excess risk was found for metformin (OR=1.30, 95% CI 1.00-1.70). However, this estimate decreased to 1.07 (95% CI 0.82-1.41) when taking into account BMI using a Monte Carlo sensitivity analysis. No significant associations were found for sulfonylureas (OR=1.16, 95% CI 0.91-1.47), thiazolidinediones (OR=0.77, 95% CI 0.48-1.24), repaglinide (OR=1.32, 95% CI 0.94-1.87), incretins (OR=1.21, 95% CI 0.63-2.32), and insulin (OR=1.19, 95% CI 0.82-1.71). Our data indicate that metformin, insulin, and other antidiabetic drugs did not meaningfully affect the risk of endometrial cancer.


Assuntos
Bases de Dados Factuais/tendências , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/epidemiologia , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Neoplasias do Endométrio/induzido quimicamente , Feminino , Seguimentos , Humanos , Hipoglicemiantes/efeitos adversos , Itália/epidemiologia , Metformina/efeitos adversos , Pessoa de Meia-Idade , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA