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Biomedical subjects

Nicole Urban

Publications and source records attributed to Nicole Urban.

18 recordsLinked to original sources
PubMed2003

The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma.

The WFDC2 (HE4) gene is amplified in ovarian carcinomas, whereas its expression in normal tissues, including ovary, is low. Although the function of the HE4 protein is unknown,it is a member of a family of stable 4-disulfide core proteins that are secreted at high levels. We therefore performed experiments to explore whether quantitation of HE4 protein levels in serum can be used as a biomarker for ovarian carcinoma. A fusion gene was constructed encoding the HE4 protein fused to a gene encoding the murine IgG2a Fc domain. Subsequently, protein produced in mammalian cells was purified by affinity chromatography and used to immunize mice to generate hybridomas specific for HE4. Hybridoma supernatants were screened for binding to a similar fusion protein that, instead, had a human immunoglobulin tail. Two hybridomas, 2H5 and 3D8, were selected that produce monoclonal antibodies to different HE4 epitopes, and a double determinant ("Sandwich") ELISA was constructed and shown to detect a signal at the 160-pg level. Blinded studies on sera from postmenopausal patients with ovarian carcinoma and controls indicate that the specificity and sensitivity of the HE4-based ELISA is equivalent to that of the CA125 assay. However, the HE4 assay may have an advantage over the CA125 assay in that it is less frequently positive in patients with nonmalignant disease.

Biomarkers, Tumor↗
PubMed2003

Serologic analysis of ovarian tumor antigens reveals a bias toward antigens encoded on 17q.

We utilized SEREX immunoscreening to identify a set of novel tumor antigens that are associated with human serous ovarian cancer and may prove useful for the early detection and treatment of this disease. Extensive screening with a panel of sera from 25 late-stage ovarian cancer patients against 3 independent cDNA libraries identified a set of 9 antigens that were immunogenic in more than 1 patient and not in a panel of 20-45 normal female serum donors. These antigens include p53, NY-ESO-1, UBQLN1, HOXB6, TOP2A, putative helicase-RUVBL (RUVBL), HMBA-inducible (HEXIM1), DDX5 and HDCMA. Ten of 25 ovarian cancer patients (40%) expressed serum IgG to at least 1 of these antigens, while 14% (4/25) had antibodies to 2 or more antigens. Unexpectedly, 4 antigens identified in this screen, DDX5, HEXIM1, TOP2A and HOXB6, are encoded within a region of 17q that also includes the genes for HER2/neu, Homeobox-B7 and BRCA1. Real-time RT-PCR analysis showed that mRNA for HER2/neu and 3 SEREX-defined antigens, TOP2A, HOXB6 and DDX5, was more abundant in ovarian tumors than most normal tissues, including normal and benign ovarian tissues, suggesting that elevated expression of genes encoded within this region of chromosome 17 is a common event in ovarian tumors. Thus, these abnormal expression patterns combined with the endogenous immune response suggests that these antigens represent potential targets for immunotherapy.

Antigens, Neoplasm↗
PubMed2003

Ovarian cancer screening.

In an ongoing effort to design an efficacious, cost-effective ovarian cancer screening method, the existing tests, CA 125 and transvaginal sonography, are being optimized and combined in a multimodal strategy, and new promising serum markers, such as mesothelin and HE4, are being developed and evaluated. Detection has been found to improve when multiple serum markers are used in a longitudinal logarithm. The parametric empirical Bayes approach improves screening algorithms by capturing the stability of markers over time in a heterogeneous population. It also has relatively simple extensions to multiple markers. The evaluation of markers increasingly accounts for characteristics of a woman that may affect her marker levels and accounts for the cancer's characteristics, histology, and grade. Receiver operating characteristic curves are helpful for evaluation because they relate a marker's sensitivity to the specificity at which it operates. Large, well-designed randomized controlled trials are under way to gauge the performance of existing screening methods.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed2003

Mammography surveillance following breast cancer.

BACKGROUND: To describe when women diagnosed with breast cancer return for their first mammography, and to identify factors predictive of women returning for mammographic surveillance. METHODS: Women who underwent mammography at facilities participating in the National Cancer Institute's Breast Cancer Surveillance Consortium (BCSC) during 1996 and who were subsequently diagnosed with ductal carcinoma in situ or invasive breast cancer were included in this study. Data from seven mammography registries were linked to population-based cancer and pathology registries. Kaplan-Meier curves were used to depict the number of months from the breast cancer diagnosis to the first mammogram within the defined follow-up period. Demographic, disease and treatment variables were included in univariate and multivariate analyses to identify factors predictive of women returning for mammography. RESULTS: Of the 2503 women diagnosed with breast cancer, 78.1% returned for mammography examination between 7 and 30 months following the diagnosis. Mammography facilities indicated that 66.8% of mammography examinations were classified as screening. Multivariate analyses found that women were most likely to undergo surveillance mammography if they were diagnosed at ages 60-69 with Stage 0, I or II breast cancer and had received radiation therapy in addition to surgery. CONCLUSIONS: While the majority of women return for mammographic surveillance following breast cancer, some important subgroups of women at higher risk for recurrence are less likely to return. Research is needed to determine why some women are not undergoing mammography surveillance after a breast cancer diagnosis and whether surveillance increases the chance of detecting tumors with a good prognosis.

Adult↗
PubMed2003

The case for early detection.

Early detection represents one of the most promising approaches to reducing the growing cancer burden. It already has a key role in the management of cervical and breast cancer, and is likely to become more important in the control of colorectal, prostate and lung cancer. Early-detection research has recently been revitalized by the advent of novel molecular technologies that can identify cellular changes at the level of the genome or proteome, but how can we harness these new technologies to develop effective and practical screening tests?

Biomarkers, Tumor↗
PubMed2003

A parametric empirical Bayes method for cancer screening using longitudinal observations of a biomarker.

A revolution in molecular technology is leading to the discovery of many biomarkers of disease. Monitoring these biomarkers in a population may lead to earlier disease detection, and may prevent death from diseases like cancer that are more curable if found early. For markers whose concentration is associated with disease progression the earliest detection is achieved by monitoring the marker with an algorithm able to detect very small changes. One strategy is to monitor the biomarkers using a longitudinal algorithm that incorporates a subject's screening history into screening decisions. Longitudinal algorithms that have been proposed thus far rely on modeling the behavior of a biomarker from the moment of disease onset until its clinical presentation. Because the data needed to observe the early pre-clinical behavior of the biomarker may take years to accumulate, those algorithms are not appropriate for timely development using new biomarker discoveries. This manuscript presents a computationally simple longitudinal screening algorithm that can be implemented with data that is obtainable in a short period of time. For biomarkers meeting only a few modest assumptions our algorithm uniformly improves the sensitivity compared with simpler screening algorithms but maintains the same specificity. It is unclear what performance advantage more complex methods may have compared with our method, especially when there is doubt about the correct model for describing the behavior of the biomarker early in the disease process. Our method was specifically developed for use in screening for cancer with a new biomarker, but it is appropriate whenever the pre-clinical behavior of the disease and/or biomarker is uncertain.

Algorithms↗
PubMed2002

Detection of ductal carcinoma in situ in women undergoing screening mammography.

BACKGROUND: With the large number of women having mammography-an estimated 28.4 million U.S. women aged 40 years and older in 1998-the percentage of cancers detected as ductal carcinoma in situ (DCIS), which has an uncertain prognosis, has increased. We pooled data from seven regional mammography registries to determine the percentage of mammographically detected cancers that are DCIS and the rate of DCIS per 1000 mammograms. METHODS: We analyzed data on 653 833 mammograms from 540 738 women between 40 and 84 years of age who underwent screening mammography at facilities participating in the National Cancer Institute's Breast Cancer Surveillance Consortium (BCSC) throughout 1996 and 1997. Mammography results were linked to population-based cancer and pathology registries. We calculated the percentage of screen-detected breast cancers that were DCIS, the rate of screen-detected DCIS per 1000 mammograms by age and by previous mammography status, and the sensitivity of screening mammography. Statistical tests were two-sided. RESULTS: A total of 3266 cases of breast cancer were identified, 591 DCIS and 2675 invasive breast cancer. The percentage of screen-detected breast cancers that were DCIS decreased with age (from 28.2% [95% confidence interval (CI) = 23.9% to 32.5%] for women aged 40-49 years to 16.0% [95% CI = 13.3% to 18.7%] for women aged 70-84 years). However, the rate of screen-detected DCIS cases per 1000 mammograms increased with age (from 0.56 [95% CI = 0.41 to 0.70] for women aged 40-49 years to 1.07 [95% CI = 0.87 to 1.27] for women aged 70-84 years). Sensitivity of screening mammography in all age groups combined was higher for detecting DCIS (86.0% [95% CI = 83.2% to 88.8%]) than it was for detecting invasive breast cancer (75.1% [95% CI = 73.5% to 76.8%]). CONCLUSIONS: Overall, approximately 1 in every 1300 screening mammography examinations leads to a diagnosis of DCIS. Given uncertainty about the natural history of DCIS, the clinical significance of screen-detected DCIS needs further investigation.

Adult↗
PubMed2002

Effectiveness of telephone counseling for mammography: results from five randomized trials.

BACKGROUND: Women over age 50 continue to be underscreened for breast cancer. The purpose of this report is to compare the effectiveness of a barrier-specific telephone counseling intervention across the five study sites of the Breast Cancer Screening Consortium (BCSC). METHODS: Each of the BCSC projects was a randomized study of the effectiveness of telephone counseling (TC) in comparison to a control condition. Eligible underusers were identified and surveyed by telephone before and after the implementation of the interventions. Data from a total of 3,461 underusers were analyzed. We tested whether significantly more women randomized to TC than to control were regular mammography users at the follow-up survey. Data were analyzed separately by site. RESULTS: Overall, TC was not significantly more effective than control in encouraging regular mammography. The pooled consortium-wide odds ratio was 1.08 (95% confidence interval: 0.91 to 1.27). CONCLUSIONS: TC has the potential to support maintenance of mammogram use. Modifications are needed to maximize this potential and additional methods should be used in conjunction with TC to reach women who are underusers of mammography.

Aged↗
PubMed2002

Costs and cost-effectiveness of a clinical intervention to increase mammography utilization in an inner city public health hospital.

BACKGROUND: Studies have demonstrated the cost-effectiveness of screening women for breast cancer; however, the cost-effectiveness of strategies to motivate women to receive breast cancer screening has been less well studied. METHODS: A total of 196 women, aged 50 to 74, who were enrolled in a public health hospital clinic, were noncompliant with mammography screening, and had at least one routine clinic appointment during the study period (15 months) were entered into a randomized, controlled trial of a motivational intervention to increase mammography rates. Costs were captured via a modified Delphi technique, accounting records, sampling of staff time logs, and an estimation of miscellaneous and overhead costs. Summary costs were calculated using Excel spread sheets. RESULTS: Overall, 49% of women who received the intervention had a mammogram within 8 weeks of an index visit compared with 22% of control women. Calculation of the cost-effectiveness of the project showed an additional cost of $151 (1996 U.S.$) for each woman receiving the intervention and $559 for each additional woman motivated to receive a mammogram. CONCLUSIONS: Cost tracking and cost-effectiveness analysis can be done when intervening in a clinical setting, thereby allowing clinics to make informed decisions about implementing programs to increase motivation of their patients to receive screening.

Aged↗
PubMed2002

Information women receive about heart attacks and how it affects their knowledge, beliefs, and intentions to act in a cardiac emergency.

In this study we investigate (a) what information women receive on acute myocardial infarction (AMI) from different information sources, (b) how women evaluate this information, and (c) how information acquisition is related to women's knowledge of AMI, personal risk perceptions, and behavioral intentions regarding a cardiac emergency. A random sample of 844 women 50 years and over were telephoned in the state of Washington. Repeated measures regression analyses showed that women receive most of their information on AMI from the mass media, even though they evaluated the media as less believable, less useful, less clear, and making less of an impression than information received from health care providers. Logistic regression analyses showed that the total number of information sources from which heart attack information was received in the past year was positively related to knowledge of AMI symptoms, beliefs about AMI, and personal risk perceptions. The results are discussed in terms of their pragmatic implications.

Adaptation, Psychological↗
PubMed2002

Use of the American College of Radiology BI-RADS to report on the mammographic evaluation of women with signs and symptoms of breast disease.

PURPOSE: To examine whether mammographic assessments and recommendations are linked as expected, based on the Breast Imaging Reporting and Data System (BI-RADS), for the evaluation of women with signs and symptoms of breast disease. MATERIALS AND METHODS: Eight mammography registries from the Breast Cancer Surveillance Consortium contributed mammographic data from 1996 through 1997 for women 25 years of age or older, with signs or symptoms of breast cancer. The association of assessments and recommendations and the relationship of self-reported symptoms to assessments are described. RESULTS: A total of 51,673 diagnostic mammograms were included in the analyses and the expected management recommendation was provided 85%-90% of the time for mammograms classified as assessment categories 1, 2, 4, or 5. Category 3 ("probably benign finding") had the most variability in associated management recommendations, with only 40% (2,998 of 7,423) of cases associated with the recommendation for short interval follow-up. Of the 1,648 category 0 mammograms ("needs additional imaging") that did not have a final assessment, 64% were recommended for additional imaging, while another 20% of the cases were recommended for either a consultation or biopsy. The number of women who reported a lump as a symptom decreased with age but was associated with higher BI-RADS assessments. CONCLUSION: BI-RADS assessment categories were generally used as intended for all categories but 0 and 3. Additional education about the use of these categories may be warranted. The inconsistencies between assessment category and management recommendations may present difficulties in conducting outcome audits.

Adult↗
PubMed2002

Concordance of breast imaging reporting and data system assessments and management recommendations in screening mammography.

PURPOSE: To examine how frequently Breast Imaging Reporting and Data System (BI-RADS) mammographic screening assessments were associated with expected clinical management recommendations. MATERIALS AND METHODS: Seven Breast Cancer Surveillance Consortium mammography registries recorded screening assessments and recommendations in 1997 to identify the proportion of women in each BI-RADS category. The first screening assessment for a woman without cancer or a prior mammogram within 9 months was associated with its independently recorded recommendation. RESULTS: Among 292,795 women, screening assessments included 269,022 (91.9%) with a "negative" or "benign finding," and 267,103 (99.3%) of these women were recommended for normal interval follow-up. Among 11,861 (4.1%) women with screening assessments of "probably benign finding," 4,782 (40.3%) were recommended for short interval follow-up as expected on the basis of the BI-RADS, but a high proportion (36.9%) were recommended for additional imaging. Among 1,625 (0.6%) women with "suspicious abnormality," most were recommended for biopsy (48.7%) or clinical examination and/or surgical consult (9.0%), but many were recommended for additional imaging (38.7%). Among 243 (0.1%) women with screening assessments "highly suggestive of malignancy," a majority were recommended for biopsy (73.3%) or clinical examination and/or surgical consult (18.1%) consistent with BI-RADS, but some were recommended for additional imaging (6.6%). CONCLUSION: BI-RADS assessments and management recommendations are consistent for negative and benign assessments, but inconsistencies were found in assessments and recommendations for mammographic abnormalities.

Adult↗
PubMed2002

Analysis of the cost-effectiveness of mammography promotion by volunteers in rural communities.

The Community Trial of Breast Cancer Screening Promotion assessed the effectiveness and cost-effectiveness of mammography promotion by community volunteer groups in rural areas using three different intervention approaches: individual counseling, community activities, and a combined intervention including both. Societal costs of the interventions were calculated and used in conjunction with measures of effectiveness to calculate cost-effectiveness in terms of cost per additional mammogram and cost per year of life saved. Methods of collecting and using cost information to assess the cost-effectiveness of community interventions are described. The Community Activities intervention was found to be the most cost-effective, at approximately $2,000 for each additional regular mammography user in the community. The cost per year of life saved associated with mammography promotion was approximately $56,000 per year of life saved. Exploratory analyses suggest that the most cost-effective method of promoting mammography use may vary with the target population.

Aged↗
PubMed2002

Use of the American College of Radiology BI-RADS guidelines by community radiologists: concordance of assessments and recommendations assigned to screening mammograms.

OBJECTIVE: This study evaluated the use of the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) by community radiologists by determining the concordance of assessment categories and recommendations assigned to screening mammograms. MATERIALS AND METHODS: The study comprised the interpretations of 82,620 consecutive screening mammograms by 18 radiologists between January 1, 1995, and December 31, 1998. For all mammograms, assessment categories and recommendations were compared to determine whether they were in accordance with BI-RADS guidelines. Overall patterns of discordance were analyzed, and comparisons of discordant patterns by assessment category, patient age, breast density, and year of examination were made. RESULTS: The overall discordance between BI-RADS assessments and recommendations was low (3%). The assessment with the highest discordance was "probably benign finding" (category 3), at 53.5%. Mammograms obtained in 1998 were almost half as likely to have assessment-recommendation discordance compared with those obtained in 1995 (2.4% vs 4.5%, respectively; odds ratio = 0.52; p < 0.001). Mammograms of women with dense breast tissue were 30% more likely to have lesions assigned discordant assessments and recommendations compared with those of women with fatty tissue (3.4% vs 2.7%, respectively; odds ratio = 1.3; p < 0.001). No differences in the patterns of discordance were found between mammograms of women younger than 50 years and those of women 50 years old and older (p = 0.10). CONCLUSION: There has been improvement in the accurate application of BI-RADS since its introduction. However, variation in the pairing of BI-RADS assessments and recommendations persists. Continued efforts to educate radiologists about the use of BI-RADS and to clarify BI-RADS terms would promote maximum consistency in this use of this reporting method.

Adult↗
PubMed2002

Generating longitudinal screening algorithms using novel biomarkers for disease.

Recent advances in molecular technology are leading to the discovery of new tumor biomarkers that may be useful for cancer screening and early diagnosis. Translating a potential screening biomarker from the laboratory to its use in patient care may require an algorithm or screening rule for its application. An algorithm that can detect the smallest deviation from a defined norm is likely to achieve the highest sensitivity, but any practical screening algorithm must do so with strict controls on test specificity to avoid false-positive results, and unnecessary patient alarm and risk. Longitudinal algorithms that make use of previous tumor marker values and trends are likely to obtain improvements over single threshold rules. Thus far, a few longitudinal screening algorithms have been proposed (e.g., using serial prostate-specific antigen values for the detection of prostate cancer and serial CA125 values for the detection of ovarian cancer), but these algorithms are not appropriate for novel tumor marker discoveries, because they rely on unverifiable assumptions that may not translate to the behavior of the new marker. The algorithm presented here is motivated by: (a) the need to develop an algorithm for early detection using novel markers; (b) the practical demands on data and specimen availability; and (c) the need to be robust enough to accommodate a wide range of tumor growth behavior. We use Parametric Empirical Bayes statistical theory to model the trajectory of markers over time in a cohort of asymptomatic healthy subjects, and use the estimated trajectory to produce person-specific thresholds that depend on the screening history of each person. The thresholds are chosen to give the person (or population) a specified false-positive rate. The resulting algorithm is simple and can be represented in a simple graph or a chart. The statistical analysis needed to generate the algorithm can be found in nearly every basic statistical package. The algorithm is highly robust and can detect a wide range of tumor behaviors. The Parametric Empirical Bayes screening algorithm should take a central role when evaluating marker discoveries for use in screening. The algorithm is particularly useful when screening with a new marker of which the behavior in the preclinical period is not well known.

Algorithms↗