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INTRODUCTION: Mammographic density is similar among women at risk of either sporadic or BRCA1/2-related breast cancer. It has been suggested that digitized mammographic images contain computer-extractable information within the parenchymal pattern, which may contribute to distinguishing between BRCA1/2 mutation carriers and non-carriers. METHODS: We compared mammographic texture pattern features in digitized mammograms from women with deleterious BRCA1/2 mutations (n = 137) versus non-carriers (n = 100). Subjects were stratified into training (107 carriers, 70 non-carriers) and testing (30 carriers, 30 non-carriers) datasets. Masked to mutation status, texture features were extracted from a retro-areolar region-of-interest in each subject's digitized mammogram. Stepwise linear regression analysis of the training dataset identified variables to be included in a radiographic texture analysis (RTA) classifier model aimed at distinguishing BRCA1/2 carriers from non-carriers. The selected features were combined using a Bayesian Artificial Neural Network (BANN) algorithm, which produced a probability score rating the likelihood of each subject's belonging to the mutation-positive group. These probability scores were evaluated in the independent testing dataset to determine whether their distribution differed between BRCA1/2 mutation carriers and non-carriers. A receiver operating characteristic analysis was performed to estimate the model's discriminatory capacity. RESULTS: In the testing dataset, a one standard deviation (SD) increase in the probability score from the BANN-trained classifier was associated with a two-fold increase in the odds of predicting BRCA1/2 mutation status: unadjusted odds ratio (OR) = 2.00, 95% confidence interval (CI): 1.59, 2.51, P = 0.02; age-adjusted OR = 1.93, 95% CI: 1.53, 2.42, P = 0.03. Additional adjustment for percent mammographic density did little to change the OR. The area under the curve for the BANN-trained classifier to distinguish between BRCA1/2 mutation carriers and non-carriers was 0.68 for features alone and 0.72 for the features plus percent mammographic density. CONCLUSIONS: Our findings suggest that, unlike percent mammographic density, computer-extracted mammographic texture pattern features are associated with carrying BRCA1/2 mutations. Although still at an early stage, our novel RTA classifier has potential for improving mammographic image interpretation by permitting real-time risk stratification among women undergoing screening mammography.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Genes BRCA1 , Genes BRCA2 , Glándulas Mamarias Humanas/anomalías , Mutación , Adulto , Anciano , Densidad de la Mama , Neoplasias de la Mama/diagnóstico , Conjuntos de Datos como Asunto , Femenino , Heterocigoto , Humanos , Mamografía , Persona de Mediana Edad , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
Strategies to bring clinical trials closer to patients gained momentum during the COVID-19 pandemic, enabling more participants to receive treatment and/or testing in their local communities. Incorporation of decentralized trial elements presents both opportunities and challenges, spanning regulatory, technical, and operational aspects. This ASCO research statement includes timely consensus-driven recommendations and a call for engagement of all research stakeholders. ASCO held multistakeholder meetings with leaders in oncology research and concluded that research-related regulatory and administrative requirements and burdens present critical barriers to decentralizing trials. One example is sponsor and contract research organization (CRO) use of US Food and Drug Administration (FDA)'s Statement of Investigator (Form 1572), which was found to exceed FDA's stated intent and used in conservative ways disproportionate to potential risks to participants and scientific integrity. As a result, research sites experience an avalanche of downstream administrative and regulatory activities that consume considerable resources. This statement recommends four key solutions to address such barriers and recalibrate regulatory and administrative expectations for decentralizing trials: (1) FDA should engage the research community in a public-private partnership to modernize standards and enable local access to trials; (2) sponsors and CROs should develop standards and protocols that accommodate flexible approaches, enable local participation, provide clarity around roles and requirements, and promote consistency; (3) research centers, networks, and sites should update policies and procedures to implement decentralized trial elements; and (4) research community should develop a streamlined, uniform mechanism to simplify regulatory data collection and documentation and use it consistently across trials. We can and must prioritize a concerted commitment to simplify and streamline regulatory requirements and practices to broaden access to and participation in cancer clinical trials.
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Ductal carcinoma in situ (DCIS) is a precursor lesion of invasive ductal carcinoma (IDC) of the breast. To understand the dynamics of genomic alterations in this progression, we used four multicolor fluorescence in situ hybridization probe panels consisting of the oncogenes COX2, MYC, HER2, CCND1, and ZNF217 and the tumor suppressor genes DBC2, CDH1, and TP53 to visualize copy number changes in 13 cases of synchronous DCIS and IDC based on single-cell analyses. The DCIS had a lower degree of chromosomal instability than the IDC. Despite enormous intercellular heterogeneity in DCIS and IDC, we observed signal patterns consistent with a nonrandom distribution of genomic imbalances. CDH1 was most commonly lost, and gain of MYC emerged during progression from DCIS to IDC. Four of 13 DCISs showed identical clonal imbalances in the IDCs. Six cases revealed a switch, and in four of those, the IDC had acquired a gain of MYC. In one case, the major clone in the IDC was one of several clones in the DCIS, and in another case, the major clone in the DCIS became one of the two major clones in the IDC. Despite considerable chromosomal instability, in most cases the evolution from DCIS to IDC is determined by recurrent patterns of genomic imbalances, consistent with a biological continuum.
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Neoplasias de la Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Intraductal no Infiltrante/genética , Inestabilidad Cromosómica/genética , Heterogeneidad Genética , Proteínas Proto-Oncogénicas c-myc/genética , Análisis de la Célula Individual/métodos , Adulto , Anciano , Biomarcadores de Tumor/genética , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Células Clonales , Progresión de la Enfermedad , Femenino , Genes Relacionados con las Neoplasias/genética , Genoma Humano/genética , Humanos , Hibridación Fluorescente in Situ , Persona de Mediana Edad , Invasividad Neoplásica , PloidiasRESUMEN
ABSTRACT: The COVID-19 pandemic posed unprecedented strain on enrollment to cancer clinical trials and their conduct. Here, we highlight an analysis using information from the National Cancer Institute (NCI) Clinical Trials Reporting Program database to describe enrollment patterns to interventional cancer treatment trials at NCI-Designated Cancer Centers during the pandemic. Enrollment to cancer treatment trials at NCI-Designated Cancer Centers decreased precipitously early in the pandemic and has not yet fully returned to the 2019 baseline as of mid-2021. We discuss possible reasons for this and how some of the changes in clinical trial conduct implemented during the pandemic may become part of the standard conduct of NCI-supported clinical trials and broaden access to trials.
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COVID-19 , Ensayos Clínicos como Asunto , Neoplasias , Participación del Paciente , COVID-19/epidemiología , Bases de Datos Factuales , Humanos , National Cancer Institute (U.S.) , Neoplasias/epidemiología , Neoplasias/terapia , Pandemias , Participación del Paciente/estadística & datos numéricos , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: To describe an approach for reporting master protocol research programs (MPRPs) that is consistent with existing good reporting practices and that uses structured information to convey the overall master protocol and design of each substudy. DESIGN: Qualitative analysis. DATA SOURCES: ClinicalTrials.gov trial registry. MAIN OUTCOME MEASURES: Established goals and related practices of the trial reporting system were outlined, examples and key characteristics of MPRPs were reviewed, and specific challenges in registering and reporting summary results to databases designed for traditional clinical trial designs that rely on a model of one study per protocol were identified. RESULTS: A reporting approach is proposed that accommodates the complex study design of MPRPs and their results. This approach involves the use of separate registration records for each substudy within one MPRP protocol (with potential exceptions noted). CONCLUSIONS: How the proposed approach allows for clear, descriptive, structured information about each substudy's prespecified design and supports timely reporting of results after completion of each substudy is described and illustrated. Although the focus is on reporting to ClinicalTrials.gov, the approach supports broader application across trial registries and results databases. This paper is intended to stimulate further discussion of this approach among stakeholders, build awareness about the need to improve reporting of MPRPs, and encourage harmonization across trial registries globally.
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Ensayos Clínicos como Asunto , Proyectos de Investigación , Bases de Datos Factuales , Humanos , Investigación Cualitativa , Sistema de RegistrosRESUMEN
The coronavirus disease 2019 (COVID-19) pandemic and related socioeconomic events have markedly changed the environment in which cancer clinical trials are conducted. These events have resulted in a substantial, immediate-term decrease in accrual to both diagnostic and therapeutic cancer investigations as well as substantive alterations in patterns of oncologic care. The sponsors of clinical trials, including the US National Cancer Institute, as well as the cancer centers and community oncology practices that conduct such studies, have all markedly adapted their models of care, usage of healthcare personnel, and regulatory requirements in the attempt to continue clinical cancer investigations while maintaining high levels of patient safety. In doing so, major changes in clinical trials practice have been embraced nationwide. There is a growing consensus that the regulatory and clinical research process alterations that have been adopted in response to the pandemic (such as the use of telemedicine visits to reduce patient travel requirements and the application of remote informed consent procedures) should be implemented long term. The COVID-19 outbreak has also refocused the oncologic clinical trials community on the need to bring clinical trials closer to patients by dramatically enhancing clinical trial access, especially for minority and underserved communities that have been disproportionately affected by the pandemic. In this commentary, changes to the program of clinical trials supported by the National Cancer Institute that could improve clinical trial availability, effectiveness, and diversity are proposed.
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Investigación Biomédica , COVID-19/epidemiología , Ensayos Clínicos como Asunto , Oncología Médica , SARS-CoV-2 , Justicia Social , HumanosRESUMEN
Elevated mammographic density (MD) is one of the strongest risk factors for sporadic breast cancer. Epidemiologic evidence suggests that MD is, in part, genetically determined; however, the relationship between MD and BRCA1/2 mutation status is equivocal. We compared MD in unaffected BRCA1/2 mutation carriers enrolled in the U.S. National Cancer Institute's Clinical Genetics Branch's Breast Imaging Study (n = 143) with women at low-to-average breast cancer risk enrolled in the same study (n = 29) or the NCI/National Naval Medical Center's Susceptibility to Breast Cancer Study (n = 90). The latter were BRCA mutation-negative members of mutation-positive families or women with no prior breast cancer, a Pedigree Assessment Tool score <8 (i.e., low risk of a hereditary breast cancer syndrome) and a Gail score <1.67. A single experienced mammographer measured MD using a computer-assisted thresholding method. We collected standard breast cancer risk factor information in both studies. Unadjusted mean percent MD was higher in women with BRCA1/2 mutations compared with women at low-to-average breast cancer risk (37.3% vs. 33.4%; P = 0.04), but these differences disappeared after adjusting for age and body mass index (34.9% vs. 36.3%; P = 0.43). We explored age at menarche, nulliparity, age at first birth, menopausal status, number of breast biopsies, and exposure to exogenous hormonal agents as potential confounders of the MD and BRCA1/2 association. Taking these factors into account did not significantly alter the results of the age/body mass index-adjusted analysis. Our results do not provide support for an independent effect of BRCA1/2 mutation status on mammographic density.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/genética , Mamografía , Adulto , Femenino , Genes BRCA1 , Genes BRCA2 , Predisposición Genética a la Enfermedad , Humanos , Interpretación de Imagen Asistida por Computador , Persona de Mediana Edad , Mutación , Factores de RiesgoRESUMEN
Breast ductal cytologic atypia is an important risk factor for sporadic breast cancer. Characterization of the associated normal breast tissue is needed to develop additional methods of risk assessment and new targets for breast cancer prevention. We conducted a prospective clinical trial evaluating women at normal-risk or at high-risk for sporadic breast cancer. Breast ductal cells were collected and studied cytologically and by gene expression profiling, and breast ductal architectural changes were studied by breast ductal endoscopy (BDE) and breast MRI. One hundred and forty subjects were studied, 70 at high risk (RR, 2.0-4.6) and 70 at normal risk. Cytologic atypia was present in 22.9% of high-risk and 25.7% of normal-risk subjects. Ductal endoscopy was performed in 89 subjects and revealed benign intraductal abnormalities, primarily intraductal fibrous webbing suggesting chronic inflammation, in 40.4% of high-risk and 5.4% of normal-risk subjects, respectively (P 2 = 0.0002). Two high-risk subjects with atypia and no normal-risk subjects with atypia developed invasive breast cancer. Gene expression profiling of ductal cells showed comparable gene expression profiles without enriched expression of previously defined oncogenic signatures in subjects with cellular atypia compared with those without atypia, and in high-risk subjects compared with normal-risk subjects (FDR > 0.5). Cytologic ductal atypia in normal-risk subjects does not appear to be of clinical significance. Atypia in women at high risk may be associated with benign and malignant breast ductal abnormalities; these characteristics of high-risk ductal cells may not be reflected in gene expression profiles.
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Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Citodiagnóstico/métodos , Medición de Riesgo/métodos , Adulto , Anciano , Biomarcadores de Tumor/genética , Mama/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal no Infiltrante/genética , Carcinoma Intraductal no Infiltrante/metabolismo , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Pronóstico , Estudios ProspectivosRESUMEN
PURPOSE: Ductal lavage has been used for risk stratification and biomarker development and to identify intermediate endpoints for risk-reducing intervention trials. Little is known about patient characteristics associated with obtaining nipple aspirate fluid (NAF) and adequate cell counts (> or =10 cells) in ductal lavage specimens from BRCA mutation carriers. METHODS: We evaluated patient characteristics associated with obtaining NAF and adequate cell counts in ductal lavage specimens from the largest cohort of women from BRCA families yet studied (BRCA1/2 = 146, mutation-negative = 23, untested = 2). Fisher's exact test was used to evaluate categorical variables; Wilcoxon nonparametric test was used to evaluate continuous variables associated with NAF or ductal lavage cell count adequacy. Logistic regression was used to identify independent correlates of NAF and ductal lavage cell count adequacy. RESULTS: From 171 women, 45 (26%) women had NAF and 70 (41%) women had ductal lavage samples with > or =10 cells. Postmenopausal women with intact ovaries compared with premenopausal women [odds ratio (OR), 4.8; P = 0.03] and women without a prior breast cancer history (OR, 5.2; P = 0.04) had an increased likelihood of yielding NAF. Having breast-fed (OR, 3.4; P = 0.001), the presence of NAF before ductal lavage (OR, 3.2; P = 0.003), and being premenopausal (OR, 3.0; P = 0.003) increased the likelihood of ductal lavage cell count adequacy. In known BRCA1/2 mutation carriers, only breast-feeding (OR, 2.5; P = 0.01) and the presence of NAF (OR, 3.0; P = 0.01) were independent correlates of ductal lavage cell count adequacy. CONCLUSIONS: Ductal lavage is unlikely to be useful in breast cancer screening among BRCA1/2 mutation carriers because the procedure fails to yield adequate specimens sufficient for reliable cytologic diagnosis or to support translational research activities.
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Neoplasias de la Mama/genética , Carcinoma Ductal de Mama/genética , Células Epiteliales/patología , Genes BRCA1 , Genes BRCA2 , Predisposición Genética a la Enfermedad/genética , Pruebas Genéticas , Pezones/patología , Adulto , Biomarcadores de Tumor , Líquidos Corporales/citología , Neoplasias de la Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Irrigación TerapéuticaRESUMEN
PURPOSE: The Oncotype Dx Recurrence Score (RS), is often employed in patients with estrogen receptor-positive, node negative (ER+LN-) breast cancer. We investigated the impact of the RS on actual chemotherapy administration and the effect of the assay on a panel of breast oncology experts. PATIENTS AND METHODS: The prospective adjuvant chemotherapy recommendations (prior to RS) and actual adjuvant therapy (after RS) for consecutive patients with ER+LN- breast cancer were recorded. After 6 months and with the same information, a panel of five experts made adjuvant therapy recommendations with and without RS and rated the strength of their recommendations. Rates of panel consensus, recommendation changes, and changes in recommendation strength were compared. RESULTS: There were 29 patients (28 women). RS results altered the plan for chemotherapy in 9 patients (31%); 7 of 13 patients (54%) initially recommended for chemotherapy did not receive it, and 2 of 16 (13%) received chemotherapy following initial recommendations against it. RS results changed the panel's chemotherapy recommendation in 7 patients (24%): 5 of 12 (42%) recommendations for changed to against, and 2 of 17 (12%) recommendations against changed to for chemotherapy. RS increased consensus by the panel 10%, but did not increase the reported strength in chemotherapy recommendations. CONCLUSIONS: RS results were associated with real-world decision changes in 31% of patients and 24% of panel recommendations and increased panel consensus by 10%. However RS did not increase the strength of panelist's recommendations.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Neoplasias de la Mama/tratamiento farmacológico , Perfilación de la Expresión Génica , Recurrencia Local de Neoplasia/prevención & control , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/patología , Neoplasias de la Mama/prevención & control , Neoplasias de la Mama Masculina/química , Neoplasias de la Mama Masculina/tratamiento farmacológico , Quimioterapia Adyuvante , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisisRESUMEN
BACKGROUND: Physical activity is being studied as a breast cancer prevention strategy. Women at risk of breast cancer report interest in lifestyle modification, but recruitment to randomized physical activity intervention studies is challenging. METHODS: We conducted an analysis of recruitment techniques used for a prospective, randomized pilot study of physical activity in women at risk of breast cancer. We evaluated differences in proportion of eligible patients, enrolled patients, and successful patients identified by each individual recruitment method. The Fisher-Freeman-Halton test (an extension of Fisher's exact test from 2 x 2 tables to general row by column tables) was used to compare the success of different recruitment strategies. RESULTS: We received 352 inquiries from women interested in participating, of whom 171 (54%) were eligible. Ninety-nine women completed a baseline activity evaluation, and 58 (34% of eligible; 16% of total inquiries) were randomized. Recruitment methods fell into three broad categories: media techniques, direct contact with potential participants, and contacts with health care providers. Recruitment strategies differed significantly in their ability to identify eligible women (p = 0.01), and women who subsequently enrolled in the study (p = 0.02). CONCLUSION: Recruitment techniques had varying success. Our data illustrate the challenges in recruiting to behavior modification studies, and provide useful information for tailoring future recruitment efforts for lifestyle intervention trials. TRIAL REGISTRATION NO(S): CDR0000393790, NCI-04-C-0276, NCI-NAVY-B05-001.
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Neoplasias de la Mama/terapia , Ejercicio Físico/fisiología , Selección de Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Neoplasias de la Mama/patología , Medios de Comunicación/estadística & datos numéricos , Femenino , Promoción de la Salud/métodos , Humanos , Aceptación de la Atención de Salud/estadística & datos numéricos , Participación del Paciente/estadística & datos numéricos , Reproducibilidad de los Resultados , Factores de RiesgoRESUMEN
Cancer clinical trials represent an important option for patients with a diagnosis of cancer and the clinician-investigators involved in their care who seek options for their disease. For all who are impacted by cancer, these studies offer opportunities for greater learning. Conducting these important studies involves several challenges, including recruiting eligible participants. To address barriers that arise over the course of these activities, the Department of Veterans Affairs (VA) and National Cancer Institute (NCI) have partnered to increase Veteran participation in oncology clinical trials. This initiative, the NCI And VA Interagency Group to Accelerate Trials Enrollment, or NAVIGATE, is focused on addressing recruitment across the VA healthcare system and finding systematic solutions related to activating, recruiting for and conducting oncology clinical trials at VA Medical Centers. Additional goals include (1) establishing a sustainable network that can serve as a model for other VA sites interested in doing cancer clinical trials, (2) recruitment of minority patients, and (3) developing best practices and policies that can be deployed across the VA healthcare system. In this manuscript, we describe the scope, organization, activities, and future directions of NAVIGATE while also highlighting key needs for successfully conducting cancer clinical trials within the VA system. This partnership between 2 large federal agencies with a shared commitment to improving cancer care may provide lessons to others who are also dedicated to helping those affected by the disease.
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Ensayos Clínicos como Asunto/organización & administración , Oncología Médica/organización & administración , Manejo de Atención al Paciente/organización & administración , Humanos , Oncología Médica/métodos , Oncología Médica/normas , National Cancer Institute (U.S.) , Atención al Paciente , Mejoramiento de la Calidad , Estados Unidos , United States Department of Veterans AffairsRESUMEN
BACKGROUND: Mammographic density is a risk factor for breast cancer. Mammographic density and breast magnetic resonance imaging (MRI) volume (MRIV) assess the amount of fibroglandular tissue in the breast. Mammographic density and MRIV can be modulated with hormonal interventions, suggesting that these imaging modalities may be useful as surrogate endpoint biomarkers for breast cancer chemoprevention trials. We evaluated the effect of raloxifene on mammographic density and MRIV in premenopausal women at increased risk for breast cancer. METHODS: Mammograms and MRI were obtained at baseline and after 1 and 2 years of 60 mg raloxifene by mouth daily for 27 premenopausal women. Mammographic percent dense area was calculated using a semiquantitative thresholding technique. T(1)-weighted spoiled gradient-echo MRI with fat suppression was used to determine breast MRIV using a semiautomatic method. Mean change in mammographic density and median change in MRIV were assessed by the Wilcoxon signed-rank test. RESULTS: No significant change in mammographic density was seen after treatment with raloxifene. Mean change after 1 year was 1% [95% confidence interval (95% CI), -3 to +5] and after 2 years was 1% (95% CI, -2 to +5). MRIV decreased on raloxifene. Median relative change in MRIV after 1 year was -17% (95% CI, -28 to -9; P = 0.0017) and after 2 years was -16% (95% CI, -31 to -4; P = 0.0004). CONCLUSIONS: In high-risk premenopausal women, mammographic density did not change on raloxifene, whereas MRIV significantly declined. Our findings suggest that MRIV is a promising surrogate biomarker in premenopausal women at increased risk for breast cancer and should be investigated further in breast cancer prevention trials.
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Neoplasias de la Mama/diagnóstico , Imagen por Resonancia Magnética/métodos , Mamografía/métodos , Premenopausia/efectos de los fármacos , Clorhidrato de Raloxifeno/administración & dosificación , Moduladores Selectivos de los Receptores de Estrógeno/administración & dosificación , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/prevención & control , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Pronóstico , Factores de Riesgo , Factores de TiempoRESUMEN
PURPOSE: This study evaluated whether phone results were equivalent to in-person result disclosure for individuals undergoing BRCA1/2 predisposition genetic testing. METHODS: A total of 111 of 136 subjects undergoing education and counseling for BRCA1/2 predisposition genetic testing agreed to randomization to phone or in-person result disclosure. Content and format for both sessions were standardized. Data from the State-Trait Anxiety Inventory and the Psychological General Well-Being index were collected at baseline and then again at 1 week and 3 months after disclosure of test results. Baseline measures were administered after the following had occurred: counseling/education session had been conducted, informed consent had been obtained, and decision to be tested had been made. Satisfaction and cost assessments were administered after the result session. At 1 week, participants were asked their preferred method of result disclosure. RESULTS: There were no differences in anxiety and general well-being measures between 50 phone and 52 in-person results disclosure. Both groups reported similar rates of satisfaction with services. Among those with a preference, 77% preferred the notification method assigned. There was a statistically significant preference for phone results among the 23% who did not prefer the method assigned. Greater costs were associated with in-person result disclosure. CONCLUSIONS: These data suggest that phone results are a reasonable alternative to traditional in-person BRCA1/2 genetic test disclosure without any negative psychologic outcomes or compromise in knowledge. However, further study is needed in a more clinically representative population to confirm these findings.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Asesoramiento Genético , Predisposición Genética a la Enfermedad , Teléfono , Adulto , Anciano , Ansiedad/etiología , Ansiedad/psicología , Proteínas Reguladoras de la Apoptosis , Femenino , Predisposición Genética a la Enfermedad/psicología , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del PacienteRESUMEN
PURPOSE: An efficient approach to education and counseling before BRCA1 and BRCA2 mutation testing is necessary for effective utilization of testing in the community. Education and counseling, when delivered individually, are limited by a shortage of trained health care providers as well as by financial and time constraints. The purpose of this study was to determine whether pretest education and counseling for breast cancer genetics in a group setting is equivalent to that provided on an individual basis. PATIENTS AND METHODS: One hundred forty-two patients at high risk for harboring a BRCA mutation were randomly assigned to group or individual education and counseling sessions. Group education was followed by brief individual counseling. Knowledge and Impact of Events Scales (IES) were administered at baseline and after education and counseling and at 1 week and 3, 6, and 12 months. Satisfaction with education and counseling was measured at completion of the session. Preferred method of education and counseling was solicited at 3 months. RESULTS: There was no difference in knowledge or IES scores between groups. When stratified by genetic test results, knowledge scores showed no difference. Regardless of group, post-test IES scores in patients with positive results were higher than patients with negative or uninformative results but returned to baseline by 12 months. Participants were equally satisfied with either method they were assigned. Significantly more time was spent per patient in individual sessions (1.25 hours) than in group education (0.74 hours). CONCLUSION: Our data suggest that group education and counseling may confer similar benefits compared with traditional individual sessions. Additional investigation of this approach in larger numbers of patients is warranted.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Predisposición Genética a la Enfermedad , Neoplasias Ováricas/genética , Neoplasias Ováricas/terapia , Educación del Paciente como Asunto/métodos , Adulto , Anciano , Actitud Frente a la Salud , Femenino , Estudios de Seguimiento , Genes BRCA1 , Genes BRCA2 , Asesoramiento Genético/métodos , Humanos , Persona de Mediana Edad , Mutación , Cooperación del Paciente , Psicoterapia de Grupo/métodos , Medición de Riesgo , Factores SocioeconómicosRESUMEN
BACKGROUND: Prolactin is a peptide hormone necessary for normal breast development that may contribute to breast tumorigenesis. Estrogen is a significant positive regulator of prolactin synthesis; therefore, raloxifene, a selective estrogen receptor modulator under study as a breast cancer prevention agent, may modulate both estradiol and prolactin levels by inhibiting estradiol from binding to its receptor. METHODS: Premenopausal women at increased risk for invasive breast cancer participated in a pilot chemoprevention trial and were given 60 mg raloxifene daily for 24 months. Fasting serum samples collected at baseline and after 12 months on drug were used to measure circulating prolactin, estradiol, and sex hormone binding globulin (SHBG) levels. RESULTS: Of the 27 subjects who completed 12 months of raloxifene, 23 had paired prolactin samples, and 20 had paired estradiol and SHBG samples. Prolactin levels did not significantly change with raloxifene treatment, but SHBG levels increased (mean change = 7.3 nmol/L; P = 0.0001; 95% confidence interval, 3.9-10.7). Estradiol (mean change = 42 pg/mL; P = 0.048; 95% confidence interval, 1-84 pg/mL) levels were elevated when comparing 15 of the 20 women with paired estradiol measurements who also had both of these samples taken during the early follicular phase of the menstrual cycle. CONCLUSIONS: This report is the first to examine the long-term effects of raloxifene on prolactin, estradiol, and SHBG levels in premenopausal women who are also at increased risk for developing invasive breast cancer. Raloxifene had no significant effect on prolactin levels but did increase estradiol and SHBG measurements.
Asunto(s)
Neoplasias de la Mama/sangre , Neoplasias de la Mama/tratamiento farmacológico , Estradiol/sangre , Premenopausia , Prolactina/sangre , Clorhidrato de Raloxifeno/uso terapéutico , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Adulto , Biomarcadores de Tumor/análisis , Carcinoma Ductal de Mama/sangre , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Intraductal no Infiltrante/sangre , Carcinoma Intraductal no Infiltrante/tratamiento farmacológico , Carcinoma Lobular/sangre , Carcinoma Lobular/tratamiento farmacológico , Femenino , Humanos , Persona de Mediana Edad , Invasividad Neoplásica/prevención & control , Proyectos Piloto , Factores de Riesgo , Globulina de Unión a Hormona Sexual/metabolismoRESUMEN
There is strong evidence that cigarette smoking causes adverse outcomes in people with cancer. However, more research is needed regarding those effects and the effects of alternative tobacco products and of secondhand smoke, the effects of cessation (before diagnosis, during treatment, or during survivorship), the biologic mechanisms, and optimal strategies for tobacco dependence treatment in oncology. Fundamentally, tobacco is an important source of variation in clinical treatment trials. Nevertheless, tobacco use assessment has not been uniform in clinical trials. Progress has been impeded by a lack of consensus regarding tobacco use assessment suitable for cancer patients. The NCI-AACR Cancer Patient Tobacco Use Assessment Task Force identified priority research areas and developed recommendations for assessment items and timing of assessment in cancer research. A cognitive interview study was conducted with 30 cancer patients at the NIH Clinical Center to evaluate and improve the measurement items. The resulting Cancer Patient Tobacco Use Questionnaire (C-TUQ) includes "Core" items for minimal assessment of tobacco use at initial and follow-up time points, and an "Extension" set. Domains include the following: cigarette and other tobacco use status, intensity, and past use; use relative to cancer diagnosis and treatment; cessation approaches and history; and secondhand smoke exposure. The Task Force recommends that assessment occur at study entry and, at a minimum, at the end of protocol therapy in clinical trials. Broad adoption of the recommended measures and timing protocol, and pursuit of the recommended research priorities, will help us to achieve a clearer understanding of the significance of tobacco use and cessation for cancer patients.
Asunto(s)
Guías como Asunto , Oncología Médica , Investigación , Uso de Tabaco , Comités Consultivos , Humanos , Oncología Médica/métodos , Oncología Médica/normas , Investigación/normas , Medición de Riesgo , Uso de Tabaco/efectos adversosRESUMEN
Early stage radiographically occult lung cancer has a high cure rate, but comprises a small fraction of all lung cancer. Abnormal sputum cytology is one indication for bronchoscopy in patients with chest imaging that is not suspicious for lung cancer. While there is good evidence that sputum cytologic findings of carcinoma, carcinoma in situ or severe atypia predict high rates of diagnosis of lung cancer, less is known of the frequency in which lung cancer is diagnosed in bronchoscopies carried out for the indication of moderate sputum atypia. One small series, published in abstract form only, reported an 8% rate of diagnosis of lung cancer in subjects bronchoscoped for moderate atypia. We tested the hypothesis that moderate sputum atypia is an indicator of occult central airway cancer in a retrospective analysis of a group of high risk subjects, defined as current or former smokers with >30 pack-years tobacco smoking and airflow obstruction with moderate atypia sputum cytology. Seventy-nine such subjects with no evidence of malignancy on chest radiograph at the time bronchoscopy was scheduled underwent white light and autofluorescence bronchoscopy. Lung cancer was found in five subjects; three had invasive squamous cell carcinomas and two had carcinoma in situ. Seven additional subjects had severe dysplasia found on endobronchial biopsy. Moderate sputum atypia may be an important marker of risk for occult endobronchial malignancy in high risk subjects.