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BACKGROUND: The Early Phase Cancer Prevention Clinical Trials Program (Consortia), led by the Division of Cancer Prevention, National Cancer Institute, supports and conducts trials assessing safety, tolerability, and cancer preventive potential of a variety of interventions. Accrual to cancer prevention trials includes the recruitment of unaffected populations, posing unique challenges related to minimizing participant burden and risk, given the less evident or measurable benefits to individual participants. The Accrual Quality Improvement Program was developed to address these challenges and better understand the multiple determinants of accrual activity throughout the life of the trial. Through continuous monitoring of accrual data, Accrual Quality Improvement Program identifies positive and negative factors in real-time to optimize enrollment rates for ongoing and future trials. METHODS: The Accrual Quality Improvement Program provides a web-based centralized infrastructure for collecting, analyzing, visualizing, and storing qualitative and quantitative participant-, site-, and study-level data. The Accrual Quality Improvement Program approaches cancer prevention clinical trial accrual as multi-factorial, recognizing protocol design, potential participants' characteristics, and individual site as well as study-wide implementation issues. RESULTS: The Accrual Quality Improvement Program was used across 39 Consortia trials from 2014 to 2022 to collect comprehensive trial information. The Accrual Quality Improvement Program captures data at the participant level, including number of charts reviewed, potential participants contacted and reasons why participants were not eligible for contact or did not consent to the trial or start intervention. The Accrual Quality Improvement Program also captures site-level (e.g. staffing issues) and study-level (e.g. when protocol amendments are made) data at each step of the recruitment/enrollment process, from potential participant identification to contact, consent, intervention, and study completion using a Recruitment Journal. Accrual Quality Improvement Program's functionality also includes tracking and visualization of a trial's cumulative accrual rate compared to the projected accrual rate, including a zone-based performance rating with corresponding quality improvement intervention recommendations. CONCLUSION: The challenges associated with recruitment and timely completion of early phase cancer prevention clinical trials necessitate a data collection program capable of continuous collection and quality improvement. The Accrual Quality Improvement Program collects cumulative data across National Cancer Institute, Division of Cancer Prevention early phase clinical trials, providing the opportunity for real-time review of participant-, site-, and study-level data and thereby enables responsive recruitment strategy and protocol modifications for improved recruitment rates to ongoing trials. Of note, Accrual Quality Improvement Program data collected from ongoing trials will inform future trials to optimize protocol design and maximize accrual efficiency.
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Ovarian and endometrial cancers are the most common gynecologic malignancies and emerging evidence suggests that lipid metabolism and subsequent inflammation are important etiologic factors for both tumors. Statins (HMG-CoA reductase inhibitors) are the most widely prescribed lipid-lowering drugs in the United States and are used by 25% of adults aged 40+ years. In addition to their cardio-protective actions, statins have anti-inflammatory effects and have demonstrated antiproliferative and apoptotic properties in cancer cell lines, supporting a potential role in cancer prevention. To appropriately quantify potential public health impact of statin use for cancer prevention, there is a great need to understand the potential risk reduction among individuals at a higher risk of gynecologic cancers, the group that will likely need to be targeted to effectively balance risk/benefit of medications repurposed for cancer prevention. In this commentary, we focus on summarizing emerging evidence suggesting that the anti-inflammatory and lipid-lowering mechanisms of statins may provide important cancer-preventive benefits for gynecologic cancers as well as outline important unanswered questions and future research directions.
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Neoplasias Endometriales , Neoplasias de los Genitales Femeninos , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Neoplasias Endometriales/prevención & control , Neoplasias Endometriales/tratamiento farmacológico , Lípidos , AntiinflamatoriosRESUMEN
BACKGROUND: Somatic pathogenic variants (PVs) in homologous recombination DNA repair (HR)-related genes found in high-grade serous ovarian carcinomas (HGSC) are not well-characterised in older patients (≥70 years). This may reflect low testing rates in older patients. METHODS: Data from 1210 HGSC patients in AACR Project GENIE and 324 patients in an independent dataset INOVATe were analysed. Cases where somatic variants could be distinguished from germline variants were included, and analysis was restricted to those with a somatic TP53 variant, to ensure cases were HGSC. RESULTS: Of 1210 patients in GENIE, 27% (n = 325) were aged ≥70 years at testing. Patients with somatic-only PVs in BRCA2 were older compared with BRCA1 (median 71 vs 60 years, p = 0.002). Median age for 21 patients with somatic-only PVs in 11 other HR-related genes ranged from 40 to 67 years. In older patients, 7% (n = 22) had somatic BRCA1/2 PVs, and 1% (n = 2) had PVs other HR-related genes; this rate was not significantly different to younger patients (<70 years), 7% (n = 62) BRCA1/2 and 2% (n = 19) other HR-related genes (p = 0.36). The overall frequency of somatic BRCA1/2 PVs was similar in INOVATe (n = 25; 7.7%) and somatic-only BRCA2 PVs were again found in older patients compared with BRCA1 (median age: at testing, 70 vs 63 years; at diagnosis, 68 vs 60 years). CONCLUSIONS: The overall frequency of somatic-only PVs in HR-related genes was similar in older and younger patients with HGSC, highlighting the importance of somatic testing irrespective of age. Limiting somatic testing by age may exclude patients who could benefit from maintenance poly(ADP-ribose) polymerase (PARP) inhibitors.
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Female carriers of pathogenic/likely pathogenic (P/LP) BRCA1/2 variants are at increased risk of developing breast and ovarian cancer. Currently, the only effective strategy for ovarian cancer risk reduction is risk-reducing bilateral salpingo-oophorectomy (RR-BSO), which carries adverse effects related to early menopause. There is ongoing investigation of inhibition of the RANK ligand (RANKL) with denosumab as a means of chemoprevention for breast cancer in carriers of BRCA1 P/LP variants. Through the NCI Division of Cancer Prevention (DCP) Early Phase Clinical Trials Prevention Consortia, a presurgical pilot study of denosumab was developed in premenopausal carriers of P/LP BRCA1/2 variants scheduled for RR-BSO with the goal of collecting valuable data on the biologic effects of denosumab on gynecologic tissue. The study was terminated early due to the inability to accrue participants. Challenges which impacted the conduct of this study included a study design with highly selective eligibility criteria and requirements and the COVID-19 pandemic. It is critical to reflect on these issues to enhance the successful completion of future prevention studies in individuals with hereditary cancer syndromes.
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Neoplasias de la Mama , COVID-19 , Neoplasias Ováricas , Femenino , Humanos , Salpingooforectomía , Denosumab/uso terapéutico , Proyectos Piloto , Pandemias , Mutación , Proteína BRCA1/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/prevención & control , Neoplasias Ováricas/epidemiología , Neoplasias de la Mama/genética , Neoplasias de la Mama/prevención & control , Neoplasias de la Mama/epidemiología , OvariectomíaRESUMEN
Next-generation tumor tissue sequencing techniques may result in the detection of putative germline pathogenic variants (PVs), raising the possibility that germline cancer predisposition could be identified from archival medical tissue samples of deceased relatives. The approach, termed traceback, is designed to inform risk management recommendations for living family members. Provider perspectives regarding traceback testing have not yet been explored, so we conducted a cross-sectional survey of Clinical Cancer Genomics Community of Practice providers regarding their attitudes and beliefs toward traceback testing. Self-reported demographics, provider characteristics, attitudes and perceived barriers were collected. We evaluated responses in the context of whether providers had previous experience with traceback testing. Data were analyzed using chi-square and Fisher's exact testing. Among 207 respondents (of 816 eligible), most were women (89.4%), white (85.5%), and not Hispanic or Latino (89.7%). US-based providers represented the majority of respondents (87.4%). Relatively, few providers 32 of 207 (15.5%) had previous experience with traceback. Among the individuals without experience in traceback, 84.0% thought there would be barriers to implementation; however, only 68.8% of individuals with previous traceback experience agreed (p = .04). Respondents in both groups thought that traceback would be valuable in their practice (82.6%, p = .22) and that they would feel comfortable discussing the concept (83.6%, p = .83), interpreting the results (72.2%, p = .24), and discussing the results with their patients (80.7%, p = .38). Patient interest and cost were seen as less of a barrier by those with experience with traceback testing. Recurrent themes obtained in open-ended responses are also presented. Overall, providers believe that traceback would be a valuable tool in their practice. Individuals with previous experience identified less barriers with implementation of this testing, highlighting an area for future research and education.
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Neoplasias , Estudios Transversales , Familia , Femenino , Genómica , Humanos , Masculino , Neoplasias/genética , Medición de Riesgo , Encuestas y CuestionariosRESUMEN
The COVID-19 pandemic overloaded health care systems around the globe and brought travel restrictions and other mandates. These effects critically impacted cancer care and conduct of clinical trials, and required medical and research communities to incorporate changes and novel flexible workflows within clinical trials and regulations to improve efficiency. We report the impact of the pandemic on cancer prevention clinical trials managed by the Division of Cancer Prevention within the NCI, focusing on participant-centric, study staff-centric and regulatory elements. Learning lessons from this challenging period, the cancer prevention community has the opportunity to incorporate many of these necessitated novel approaches to future design of clinical trials, to streamline and improve clinical trial efficiency and impact.
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COVID-19 , Ensayos Clínicos como Asunto , Neoplasias , COVID-19/epidemiología , Atención a la Salud , Humanos , National Cancer Institute (U.S.) , Neoplasias/prevención & control , Pandemias , Proyectos de Investigación , Estados Unidos/epidemiologíaRESUMEN
The Division of Cancer Prevention in the NCI sponsored a Roundtable with primary care providers (PCP) to determine barriers for integrating cancer prevention within primary care and discuss potential opportunities to overcome these barriers. The goals were to: (i) assess the cancer risk assessment tools available to PCPs; (ii) gather information on use of cancer prevention resources; and (iii) understand the needs of PCPs to facilitate the implementation of cancer prevention interventions beyond routine screening and interventions. The Roundtable discussion focused on challenges and potential research opportunities related to: (i) cancer risk assessment and management of high-risk individuals; (ii) cancer prevention interventions for risk reduction; (iii) electronic health records/electronic medical records; and (iv) patient engagement and information dissemination. Time constraints and inconsistent/evolving clinical guidelines are major barriers to effective implementation of cancer prevention within primary care. Social determinants of health are important factors that influence patients' adoption of recommended preventive interventions. Research is needed to determine the best means for implementation of cancer prevention across various communities and clinical settings. Additional studies are needed to develop tools that can help providers collect clinical data that can enable them to assess patients' cancer risk and implement appropriate preventive interventions.
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Neoplasias , Atención Primaria de Salud , Humanos , Neoplasias/prevención & controlRESUMEN
Approximately 12% of routinely examined fallopian tubes of endometrial carcinoma (EC) cases have intraluminal tumor cells (ILTCs). ILTC associations with EC characteristics and outcomes are understudied, and unknown in serially examined and embedded tubal fimbriae. Glass slides of serially examined and embedded tubal fimbriae for 371 EC cases were independently reviewed by 2 pathologists who recorded ILTC presence and characterized them as mucosal if involved and floating if not. Disagreements were reviewed by a third pathologist, and agreement between any 2 determined final ILTC status. Clinico-pathologic associations and ILTC presence were tested for significance ( P <0.05) by univariable analysis, and stage and histotype determinants were included in a multivariable analysis. The Kaplan-Meier estimates and log-rank tests compared overall and EC-specific survival, and Cox proportional regression estimated hazard ratios. ILTCs were present in 56 (15.1%) cases: 30 mucosal and 26 floating. FIGO stage 3/4, lymph-vascular space invasion, deep myometrial invasion, nonendometrioid histotype, and adjunctive chemotherapy were significantly associated with ILTC presence, and only stage was significant in the multivariable analysis. Overall, 61 women died: 30 of whom died of EC. ILTCs were nonsignificantly associated with higher overall and EC-specific mortality and mucosal ILTCs had the highest hazard ratios (1.64 and 1.89, respectively). Serially examined and embedded tubal fimbriae have a higher prevalence of ILTCs than routinely examined tubes, and high FIGO stage is an independent determinant. A prognostic effect was not found, but the higher trending hazard ratios suggest additional study is needed to determine whether ILTCs and in particular mucosal ILTCs adversely affect prognosis.
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Neoplasias Endometriales , Trompas Uterinas , Neoplasias Endometriales/patología , Trompas Uterinas/patología , Femenino , Humanos , Estadificación de Neoplasias , Pelvis/patología , PronósticoRESUMEN
As clinical guidelines for cancer prevention refer individuals to primary care physicians (PCP) for risk assessment and clinical management, PCPs may be expected to play an increasing role in cancer prevention. It is crucial that PCPs are adequately supported to assess an individual's cancer risk and make appropriate recommendations. The objective of this study is to assess use, familiarity, attitude, and behaviors of PCPs regarding breast and ovarian cancer risk and prevention, to better understand the factors that influence their prescribing behaviors. We conducted a cross-sectional, web-based survey of PCPs in the United States, recruited from an opt-in healthcare provider panel. Invitations were sent in batches until the target sample size of 750 respondents (250 each for obstetrics/gynecology, internal medicine, and family medicine) was met. Self-reported use of breast/ovarian cancer risk assessments was low (34.7%-59.2%) compared with discussion of cancer family history (96.9%), breast exams (87.1%), and mammograms (92.8%). Although most respondents (48.0%-66.8%) were familiar with cancer prevention interventions, respondents who reported to be less familiar were more likely to report cautious attitudes. When presented with hypothetical cases depicting patients at different breast/ovarian cancer risks, up to 34.0% of respondents did not select any of the clinically recommended course(s) of action. This survey suggests that PCP use of breast/ovarian cancer risk assessment tools and ability to translate the perceived risks to clinical actions is variable. Improving implementation of cancer risk assessment and clinical management guidelines within primary care may be necessary to improve the appropriate prescribing of cancer prevention interventions.Prevention Relevance: Primary care physicians are becoming more involved in cancer prevention management, so it is important that cancer risk assessment and medical society guideline recommendations for cancer prevention are better integrated into primary care to improve appropriate prescribing of cancer prevention interventions and help reduce cancer risk.
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Neoplasias de la Mama/prevención & control , Detección Precoz del Cáncer/estadística & datos numéricos , Neoplasias Ováricas/prevención & control , Médicos de Atención Primaria/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adulto , Anciano , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Competencia Clínica/estadística & datos numéricos , Estudios Transversales , Detección Precoz del Cáncer/métodos , Detección Precoz del Cáncer/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/epidemiología , Médicos de Atención Primaria/normas , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/normas , Medición de Riesgo/normas , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Encuestas y Cuestionarios/estadística & datos numéricos , Estados UnidosRESUMEN
The Division of Cancer Prevention and the Division of Cancer Biology at the National Cancer Institute and the Gynecologic Health and Disease Branch in the National Institute of Child Health and Human Development organized a workshop in April 2019 to explore current insights into the progression of gynecologic cancers from benign conditions. Working groups were formed based on 3 gynecologic disease types: (1) Endometriosis or Endometrial Cancer and Endometrial-Associated Ovarian Cancer, (2) Uterine Fibroids (Leiomyoma) or Leiomyosarcoma, and (3) Adenomyosis or Adenocarcinoma. In this report, we highlight the key questions and current challenges that emerged from the working group discussions and present potential research opportunities that may advance our understanding of the progression of gynecologic benign conditions to cancer.
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Enfermedades de los Genitales Femeninos/patología , Neoplasias de los Genitales Femeninos/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/terapia , Adenomiosis/diagnóstico , Adenomiosis/genética , Adenomiosis/patología , Adenomiosis/terapia , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/terapia , Progresión de la Enfermedad , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Neoplasias Endometriales/terapia , Endometriosis/diagnóstico , Endometriosis/genética , Endometriosis/patología , Endometriosis/terapia , Estrógenos , Femenino , Enfermedades de los Genitales Femeninos/diagnóstico , Enfermedades de los Genitales Femeninos/genética , Enfermedades de los Genitales Femeninos/terapia , Neoplasias de los Genitales Femeninos/diagnóstico , Neoplasias de los Genitales Femeninos/genética , Neoplasias de los Genitales Femeninos/terapia , Humanos , Leiomioma/diagnóstico , Leiomioma/genética , Leiomioma/patología , Leiomioma/terapia , Leiomiosarcoma/diagnóstico , Leiomiosarcoma/genética , Leiomiosarcoma/patología , Leiomiosarcoma/terapia , National Cancer Institute (U.S.) , National Institute of Child Health and Human Development (U.S.) , Células Madre Neoplásicas , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapia , Terminología como Asunto , Estados Unidos , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologíaRESUMEN
BACKGROUND: Basal-like breast cancer (BLBC) is a poorly characterised, heterogeneous disease. Patients are diagnosed with aggressive, high-grade tumours and often relapse with chemotherapy resistance. Detailed understanding of the molecular underpinnings of this disease is essential to the development of personalised therapeutic strategies. Inhibitor of differentiation 4 (ID4) is a helix-loop-helix transcriptional regulator required for mammary gland development. ID4 is overexpressed in a subset of BLBC patients, associating with a stem-like poor prognosis phenotype, and is necessary for the growth of cell line models of BLBC through unknown mechanisms. METHODS: Here, we have defined unique molecular insights into the function of ID4 in BLBC and the related disease high-grade serous ovarian cancer (HGSOC), by combining RIME proteomic analysis, ChIP-seq mapping of genomic binding sites and RNA-seq. RESULTS: These studies reveal novel interactions with DNA damage response proteins, in particular, mediator of DNA damage checkpoint protein 1 (MDC1). Through MDC1, ID4 interacts with other DNA repair proteins (γH2AX and BRCA1) at fragile chromatin sites. ID4 does not affect transcription at these sites, instead binding to chromatin following DNA damage. Analysis of clinical samples demonstrates that ID4 is amplified and overexpressed at a higher frequency in BRCA1-mutant BLBC compared with sporadic BLBC, providing genetic evidence for an interaction between ID4 and DNA damage repair deficiency. CONCLUSIONS: These data link the interactions of ID4 with MDC1 to DNA damage repair in the aetiology of BLBC and HGSOC.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Carcinoma Basocelular/genética , Carcinoma Basocelular/metabolismo , Proteínas Inhibidoras de la Diferenciación/genética , Proteínas Inhibidoras de la Diferenciación/metabolismo , Animales , Apoptosis/fisiología , Neoplasias de la Mama/patología , Carcinoma Basocelular/patología , Diferenciación Celular/fisiología , Línea Celular Tumoral , Proliferación Celular/fisiología , Cromatina/genética , Cromatina/metabolismo , Daño del ADN , Femenino , Xenoinjertos , Humanos , Ratones , Ratones Endogámicos NOD , Ratones SCID , Pronóstico , Proteogenómica , Células Tumorales CultivadasRESUMEN
Cancer-associated fibroblasts (CAFs) are the most abundant cell type in the tumor microenvironment and are responsible for producing the desmoplastic reaction that is a poor prognostic factor in ovarian cancer. Long non-coding RNAs (lncRNAs) have been shown to play important roles in cancer. However, very little is known about the role of lncRNAs in the tumor microenvironment. We aimed to identify lncRNAs expressed in ovarian CAFs that were associated with patient survival and used computational approaches to predict their function. Increased expression of 9 lncRNAs and decreased expression of 1 lncRNA in ovarian CAFs were found to be associated with poorer overall survival. A "guilt-by-association" approach was used to predict the function of these lncRNAs. In particular, MIR155HG was predicted to play a role in immune response. Further investigation revealed high MIR155HG expression to be associated with higher infiltrates of immune cell subsets. In conclusion, these data indicate expression on several lncRNAs in CAFs are associated with patient survival and are likely to play an important role in regulating CAF function.
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Fibroblastos Asociados al Cáncer/metabolismo , Neoplasias Ováricas/genética , Neoplasias Ováricas/mortalidad , ARN Largo no Codificante/genética , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/patología , Pronóstico , ARN Largo no Codificante/metabolismo , Análisis de Supervivencia , Microambiente TumoralRESUMEN
PURPOSE: Acceptability and uptake of cancer preventive interventions is associated with physician recommendation, which is dependent on physician familiarity with available preventive options. The goal of this study is to evaluate cancer prevention perceptions, understanding of breast and ovarian cancer risk factors, and prescribing behaviors of primary care physicians. METHODS: We conducted cross-sectional. Web-based survey of 750 primary care physicians (250 each for obstetrics/gynecology, internal medicine, and family medicine) in the United States. Survey respondents were recruited from an opt-in health care provider panel. RESULTS: Perception of importance and the practice of recommending general and cancer-specific preventive screenings and interventions significantly differed by provider type. These perceptions and behaviors reflected the demographics of the population that the primary care physicians see within their respective practices. The majority of respondents recognized genetic/hereditary risk factors for breast or ovarian cancer, while epidemiologic or clinical risk factors were less frequently recognized. Prescribing behaviors were related to familiarity with the interventions, with physicians indicating that they more frequently reinforced a specialist's recommendation rather than prescribed a preventive intervention. CONCLUSIONS: Cancer prevention perceptions, recognition of cancer risk factors, and prescribing behaviors differ among practice types and were related to familiarity with preventive options. Cancer prevention education and risk assessment resources should be more widely available to primary care physicians.
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Neoplasias de la Mama/prevención & control , Neoplasias Ováricas/prevención & control , Pautas de la Práctica en Medicina/estadística & datos numéricos , Atención Primaria de Salud/métodos , Medición de Riesgo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/etiología , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Ováricas/etiología , Atención Primaria de Salud/estadística & datos numéricos , Medición de Riesgo/métodos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
Mucinous ovarian carcinoma (MOC) is a unique subtype of ovarian cancer with an uncertain etiology, including whether it genuinely arises at the ovary or is metastatic disease from other organs. In addition, the molecular drivers of invasive progression, high-grade and metastatic disease are poorly defined. We perform genetic analysis of MOC across all histological grades, including benign and borderline mucinous ovarian tumors, and compare these to tumors from other potential extra-ovarian sites of origin. Here we show that MOC is distinct from tumors from other sites and supports a progressive model of evolution from borderline precursors to high-grade invasive MOC. Key drivers of progression identified are TP53 mutation and copy number aberrations, including a notable amplicon on 9p13. High copy number aberration burden is associated with worse prognosis in MOC. Our data conclusively demonstrate that MOC arise from benign and borderline precursors at the ovary and are not extra-ovarian metastases.
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Adenocarcinoma Mucinoso/genética , Carcinoma Epitelial de Ovario/genética , Perfilación de la Expresión Génica/métodos , Neoplasias Ováricas/genética , Adenocarcinoma Mucinoso/clasificación , Adenocarcinoma Mucinoso/metabolismo , Carcinoma Epitelial de Ovario/clasificación , Carcinoma Epitelial de Ovario/metabolismo , Estudios de Cohortes , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Mutación , Neoplasias Ováricas/clasificación , Neoplasias Ováricas/metabolismo , Análisis de Secuencia de ADN/métodos , Análisis de SupervivenciaRESUMEN
Individuals at high risk for cancer, including those already diagnosed with premalignant lesions, can potentially benefit from chemopreventive interventions to reduce cancer risk. However, uptake and acceptability have been hindered due to the risk of systemic toxicity and other adverse effects. Locally delivered chemopreventive agents, where direct action on the primary organ may limit systemic toxicity, are emerging as an option for high-risk individuals. While a number of clinical trials support the development of chemopreventive agents, it is crucial to understand the factors and barriers that influence their acceptability and use. We conducted 36 focus groups with 198 individuals at average and high risk of breast/ovarian, gynecologic, and head/neck/oral and lung cancers to examine the perceptions and acceptability of chemopreventive agents. Participants' willingness to use chemopreventive agents was influenced by several factors, including perceived risk of cancer, skepticism around prevention, previous knowledge of chemopreventive agents, support from trusted sources of health information, participation in other cancer-related risk-reduction activities, previous experience with similar modalities, cost, regimen, side effects, and perceived effectiveness of the preventive intervention. Our findings indicate that individuals may be more receptive to locally delivered chemopreventive agents if they perceive themselves to be at high risk for cancer and are given the necessary information regarding regimen and side effects to make an informed decision. Clinical trials that collect additional patient-centered data including side effects and how these interventions fit into an individual's lifestyle are imperative to improve uptake of chemopreventive agents.
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Quimioprevención/psicología , Toma de Decisiones , Conocimientos, Actitudes y Práctica en Salud , Neoplasias/prevención & control , Educación del Paciente como Asunto , Conducta de Reducción del Riesgo , Femenino , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Neoplasias/psicología , Investigación CualitativaRESUMEN
PURPOSE: To evaluate factors associated with compliance to the National Comprehensive Cancer Network (NCCN) guidelines for BRCA1/2 testing and identify groups who are at risk of under- and over-use of BRCA1/2 testing. METHODS: Data included 20,758 women from Dr. Susan Love Research Foundation's The Health of Women (HOW) Study®. Multinomial logistic regression was used to examine the association of socioeconomic and demographic characteristics with whether the woman was over-, under-, or appropriately tested for BRCA1/2 mutations, per 2015 NCCN guidelines. RESULTS: 3894 women (18.8%) reported BRCA1/2 testing. 5628 (27.1%) women who met NCCN criteria for testing were not tested. Among women with a history of breast cancer, those without health insurance were more likely to be under-tested (OR 2.04, 95% CI 1.15-3.60) than those with managed care insurance, and higher education was associated with a lower likelihood of under-testing (Graduate/professional degree OR 0.71, 95% CI 0.55-0.91). CONCLUSION: Almost 30% of women were under-tested, indicating that many high-risk women who may benefit from genetic testing are currently being missed. Without appropriate testing, providers are unable to tailor screening recommendations to those carrying mutations who are at highest risk. Patient and healthcare provider education and outreach targeted to low-income and under-served populations may assist in reducing under-testing.
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Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Genes BRCA1 , Genes BRCA2 , Salud de la Mujer , Neoplasias de la Mama/diagnóstico , Femenino , Pruebas Genéticas , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Guías de Práctica Clínica como Asunto , Factores de RiesgoRESUMEN
In 2018, there will be approximately 22,240 new cases of ovarian cancer diagnosed and 14,070 ovarian cancer deaths in the United States. Herein, the American Cancer Society provides an overview of ovarian cancer occurrence based on incidence data from nationwide population-based cancer registries and mortality data from the National Center for Health Statistics. The status of early detection strategies is also reviewed. In the United States, the overall ovarian cancer incidence rate declined from 1985 (16.6 per 100,000) to 2014 (11.8 per 100,000) by 29% and the mortality rate declined between 1976 (10.0 per 100,000) and 2015 (6.7 per 100,000) by 33%. Ovarian cancer encompasses a heterogenous group of malignancies that vary in etiology, molecular biology, and numerous other characteristics. Ninety percent of ovarian cancers are epithelial, the most common being serous carcinoma, for which incidence is highest in non-Hispanic whites (NHWs) (5.2 per 100,000) and lowest in non-Hispanic blacks (NHBs) and Asians/Pacific Islanders (APIs) (3.4 per 100,000). Notably, however, APIs have the highest incidence of endometrioid and clear cell carcinomas, which occur at younger ages and help explain comparable epithelial cancer incidence for APIs and NHWs younger than 55 years. Most serous carcinomas are diagnosed at stage III (51%) or IV (29%), for which the 5-year cause-specific survival for patients diagnosed during 2007 through 2013 was 42% and 26%, respectively. For all stages of epithelial cancer combined, 5-year survival is highest in APIs (57%) and lowest in NHBs (35%), who have the lowest survival for almost every stage of diagnosis across cancer subtypes. Moreover, survival has plateaued in NHBs for decades despite increasing in NHWs, from 40% for cases diagnosed during 1992 through 1994 to 47% during 2007 through 2013. Progress in reducing ovarian cancer incidence and mortality can be accelerated by reducing racial disparities and furthering knowledge of etiology and tumorigenesis to facilitate strategies for prevention and early detection. CA Cancer J Clin 2018;68:284-296. © 2018 American Cancer Society.
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Carcinoma/epidemiología , Neoplasias Ováricas/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , American Cancer Society , Carcinoma/diagnóstico , Detección Precoz del Cáncer , Femenino , Disparidades en el Estado de Salud , Humanos , Incidencia , Persona de Mediana Edad , Neoplasias Ováricas/diagnóstico , Pronóstico , Estados Unidos/epidemiologíaRESUMEN
Background: Chemoresistance is a major challenge in ovarian cancer treatment, resulting in poor survival rates. Identifying markers of treatment response is imperative for improving outcome while minimizing unnecessary side effects. We have previously demonstrated that expression of transducin-like enhancer of split 3 (TLE3) is associated with favorable progression-free survival in taxane-treated ovarian cancer patients with nonserous histology. The purpose of this study was to perform an independent evaluation of the association of TLE3 expression with response to taxane-based chemotherapy in nonserous ovarian cancer, to validate its role as a potential therapeutic response marker for taxane-based chemotherapy.Methods: We performed immunohistochemical staining of TLE3 on ovarian cancer specimens from the Australian Ovarian Cancer Study, the Westmead Gynaecological Oncology Biobank, and Memorial Sloan Kettering Cancer Center. Progression-free survival and overall survival were assessed to validate an association between TLE3 expression and response to taxane therapy that we previously observed in a smaller study.Results: Expression of TLE3 was associated with favorable outcome only in patients who had received paclitaxel as part of their treatment regimen for both 3-year progression-free survival (n = 160; HR, 0.56; P = 0.03) and 5-year overall survival (HR, 0.53; P = 0.04). Further analysis revealed that the predictive association between TLE3 expression and outcome was strongest in tumors with clear cell histology.Conclusions: The association between high TLE3 expression and a favorable response to taxane-containing chemotherapy regimens was validated in patients with nonserous ovarian cancer.Impact: TLE3 expression may serve as a marker of chemosensitivity in taxane-treated patients with nonserous histologies. Cancer Epidemiol Biomarkers Prev; 27(6); 680-8. ©2018 AACR.
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Proteínas Co-Represoras/metabolismo , Neoplasias Ováricas/genética , Hidrocarburos Aromáticos con Puentes , Estudios de Cohortes , Femenino , Humanos , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Tasa de Supervivencia , TaxoidesRESUMEN
The utility of circulating DNA as a source of clinical biomarkers in blood is limited by its low concentration and small fragment size. Effective purification methods can maximize circulating DNA yield and contribute to the success of downstream protocols. We describe the evaluation of 4 commercial DNA purification kits-QIAamp Circulating Nucleic Acids kit, QIAamp DNA Blood Mini kit, QIAamp Ultrasens Virus kit and the QIASymphony DSP Virus kit-for the extraction of high and low molecular weight DNA from blood plasma. Using qPCR to quantitate endogenous Alu sequences, as well as spiked exogenous high and low molecular weight zebrafish DNA, we found that the Circulating Nucleic Acids kit and the DSP kit were both efficient at purifying DNA from plasma regardless of fragment size, whereas the DNA Blood Mini kit was only able to effectively extract high molecular weight DNA. The Ultrasens Virus Kit produced the lowest yields for both large and small fragments. The use of carrier RNA with the Circulating Nucleic Acids and the DSP kits improved yields. Appropriate choice of kit can be an important factor in determining experiment outcome.
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Ácidos Nucleicos Libres de Células/sangre , Animales , Ácidos Nucleicos Libres de Células/química , Humanos , Biopsia Líquida/métodos , Peso Molecular , Reacción en Cadena de la Polimerasa/métodos , Pez CebraRESUMEN
OBJECTIVE: Many high-grade serous carcinomas initiate in fallopian tubes as serous tubal intraepithelial carcinoma (STIC), a microscopic lesion identified with specimen processing according to the Sectioning and Extensive Examination of the Fimbria protocol (SEE-Fim). Given that the tubal origin of these cancers was recently recognized, we conducted a survey of pathology practices to assess processing protocols that are applied to gynecologic surgical pathology specimens in clinical contexts in which finding STIC might have different implications. METHODS: We distributed a survey electronically to the American Society for Clinical Pathology list-serve to determine practice patterns and compared results between practice types by chi-square (χ2) tests for categorical variables. Free text comments were qualitatively reviewed. RESULTS: Survey responses were received from 159 laboratories (72 academic, 87 non-academic), which reported diverse specimen volumes and percentage of gynecologic samples. Overall, 74.1% of laboratories reported performing SEE-Fim for risk-reducing surgical specimens (82.5% academic versus 65.7% non-academic, pâ¯<â¯0.05). In specimens from surgery for benign indications in which initial microscopic sections showed an unanticipated suspicious finding, 75.9% of laboratories reported using SEE-Fim to process the remainder of the specimen (94.8% academic versus 76.4% non-academic, pâ¯<â¯0.01), and 84.6% submitted the entire fimbriae. CONCLUSIONS: Changes in the theories of pathogenesis of high-grade serous carcinoma have led to implementation of pathology specimen processing protocols that include detailed analysis of the fallopian tubes. These results have implications for interpreting trends in cancer incidence data and considering the feasibility of developing a bank of gynecologic tissues containing STIC or early cancer precursors.