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PubMed2001

Trends in biomarker research for cancer detection.

A key challenge in cancer control and prevention is detection of the disease as early as possible, enabling effective interventions and therapies to contribute to reduction in mortality and morbidity. Biomarkers are important as molecular signposts of the physiological state of a cell at a specific time. Active genes, their respective protein products, and other organic chemicals made by the cell create these signposts. As a normal cell progresses through the complex process of transformation to a cancerous state, biomarkers could prove vital for the identification of early cancer and people at risk of developing cancer. We discuss current research into the genetic and molecular signatures of cells, including microsatellite instability, hypermethylation and single-nucleotide polymorphisms. The use of genomic and proteomic high-throughput technology platforms to facilitate detection of early cancer by means of biomarkers, and issues on the analysis, validation, and predictive value of biomarkers based on these technologies are also discussed. We report on recent advances in identifying sources of biomarkers that can be accessed by noninvasive techniques, such as buccal-cell isolates, as well as traditional sources such as serum or plasma. We also focus on the work of the Early Detection Research Network at the National Cancer Institute, harnessing expertise from leading national and international institutions, to identify and validate biomarkers for the detection of precancerous and cancerous cells in assessing risk of cancer. The network also has a role in linking discovery to process development, resulting in early detection tests and clinical assessment.

Biomarkers, Tumor↗
PubMed2001

Patterns and predictors of the breast cancer detection methods in women under 45 years of age (United States).

OBJECTIVES: Few studies have examined methods by which breast cancers are detected, and only one study has been published on predictors of those methods. This study examined patterns and predictors of breast cancer detection methods during 1990-1992 among women age 20-44. METHODS: In-person interview and medical record data were obtained during a population-based case-control study of 1619 women newly diagnosed with breast cancer in three areas of the United States (US). RESULTS: Seventy-one percent of the cancers were identified by self-detection, 9% by routine clinical breast exam (CBE), and 20% by routine mammography. Cancers detected by mammography and CBE, but not those detected by breast self-exam, were much more likely to be early-stage. Detection by mammography increased with age, and a history of mammography use was associated with detection by mammography or CBE. Several commonly studied predictors of screening utilization in the US population were associated with CBE detection, but were less clearly related to or unrelated to mammography detection. CONCLUSION: Findings suggest that, during the 1990s in the US, most breast cancers among women under age 45, including those age 40-44, were self-detected. Few factors other than age and prior screening are verified predictors of method of breast cancer detection.

Adult↗
PubMed2004

Multi-phasic CT arterial portography and CT hepatic arteriography improving the accuracy of liver cancer detection.

AIM: To evaluate the value of multi-phasic CT arterial portography (CTAP) and CT hepatic arteriography (CTHA) in differential diagnosis of liver diseases, and to improve the specificity of CTAP and CTHA for liver cancer detection. METHODS: From January 1999 to December 2002, multi-phasic CTAP and CTHA were performed in 20 patients with suspected liver disease. CT scanning was begun 25 s, 60 s and 120 s for the early-, late- and delayed-phase CTAP examinations, and 6 sec, 40 s and 120 s for the early-, late- and delayed-phase CTHA examinations respectively, after a transcatheter arterial injection of non-ionic contrast material. If a lesion was diagnosed as a liver cancer, transcatheter hepatic arterial chemoembolization (TACE) treatment was performed, and the follow-up CT was performed three or four weeks later. RESULTS: All eighteen HCCs in 12 cases were shown as nodular enhancement on early-phasic CTHA. The density of the whole tumor decreased rapidly on late and delayed phases, and the edge of 12 tumors (12/18) remained relatively hyperdense compared with the surrounding liver tissue, and demonstrated as rim enhancement. All HCCs were shown as perfusion defect nodules on multi-phasic CTAP. Five tumors (5/18) were shown as rim enhancement on delayed-phasic CTAP. Rim enhancement was shown as 1 to 2-mm-wide irregular, uneven and discontinuous circumferential enhancement at late-, and delayed-phase of CTHA or CTAP. Five pseudolesions and 4 hemoangiomas were found in multi-phasic CTAP and CTHA. No pseudolesions and hemoangiomas were shown as rim enhancement on late- or delayed-phasic CTHA and CTAP. CONCLUSION: Multi-phasic CTAP and CTHA could help to recognize the false-positive findings in CTAP and CTHA images, and improve the accuracy of CTAP and CTHA of liver cancer detection.

Adult↗
PubMed1995

Agreement between self-reported early cancer detection practices and medical audits among Hispanic and non-Hispanic white health plan members in northern California.

BACKGROUND: Using the medical records of a large, prepaid health plan, our purpose was to assess the accuracy of self-reported data on cancer detection practices and to evaluate any differences in accuracy between Hispanics and non-Hispanic whites. METHODS: Data were collected on six procedures: mammography, clinical breast examination, Pap smear, sigmoidoscopy, fecal occult blood tests, and digital rectal examination. We audited the medical records of 815 randomly selected Hispanic and 483 non-Hispanic white members of the Kaiser Permanente Medical Care Program in Northern California. All responded to a telephone survey. Using a standardized form, we recorded any of the six target examinations that had been performed within 5 years of the telephone interview. We then compared the times of the most recent screening tests as reported in the telephone survey with those in the medical record. RESULTS: For the 2 years before the telephone interview, self-reports for screening tests overestimated the actual rates at which these tests were performed as documented in the medical records. Lack of agreement between self-report and medical record audits was substantial for all screening procedures except sigmoidoscopy. Hispanic members had fewer procedures done for most tests, but the differences were not statistically significant. Overestimates in self-reported screening rates did not differ substantially between Hispanics and non-Hispanic whites. CONCLUSIONS: Self-reported data on early cancer detection procedures can substantially overestimate their occurrence among both non-Hispanic white and Hispanic populations. These findings confirm earlier findings for Pap smear and affect decisions on cancer prevention procedures that rely on the accuracy of self-reported data.

Breast Neoplasms↗
PubMed2004

Significance of cancer detection in the anterior lateral horn on systematic prostate biopsy: the effect on pathological findings of radical prostatectomy specimens.

OBJECTIVE: To clarify the significance of cancer detection in the anterior lateral horn (ALH) on systematic prostate biopsy in relation to its effect on the pathological findings from retropubic radical prostatectomy (RRP) specimens. PATIENTS AND METHODS: The study included 84 consecutive patients who underwent RRP at our institution between January 1999 and December 2002, after being diagnosed as having prostate cancer, based on systematic prostate biopsies that included the areas taken by standard sextant biopsies and the bilateral ALHs. Several clinicopathological factors of these patients were analysed in relation to the presence or absence of cancer in the ALH on systematic biopsy. RESULTS: Of the 84 patients, cancer was detected in the ALH in 44 (group A), but not in the remaining 40 (group B). There were no significant differences in age, preoperative serum prostate-specific antigen level, or prostate volume between the groups. However, the incidence of bilateral positive cores and the percentage of positive biopsy cores in group A were significantly higher than those in group B. Pathological examinations of RRP specimens showed no significant differences in the incidence of lymphatic invasion, vascular invasion and perineural invasion, or Gleason score between the groups, but group A had a significantly larger tumour volume and higher incidence of extraprostatic disease than group B. CONCLUSIONS: Despite similar biological tumour characteristics and irrespective of the cancer location in the ALH, advanced and extensive disease frequently involves the ALH. Therefore, more aggressive treatment should be considered if cancer is detected in the ALH by systematic prostate biopsy.

Aged↗
PubMed1995

Assessment of sextant biopsy of the prostate for detecting cancer prior to therapy in patients clinically diagnosed as benign prostatic hyperplasia.

Pathological results and perioperative morbidity were compared in 199 patients who had undergone prostatectomy and/or biopsy in order to determine the extent to which systematic biopsy is effective for detecting prostate cancer prior to therapy in patients clinically diagnosed as having benign prostatic hyperplasia. Seventeen (8.5%) cancers were detected in 199 patients following surgery and/or biopsy. Digitally-guided biopsy as a means of detecting prostate cancer was found to be just as effective as ultrasound-guided biopsy. Seven (12.5%) cancers were detected in 56 patients who had undergone biopsy and transurethral resection. Preprostatectomy biopsy detected only two of three patients with stage T1b disease. All four stage T1a and one stage T1b failed to be diagnosed. Of 90 patients who had biopsy prior to surgery other than TURP, seven (7.8%) cancers were found. Four of these were advanced. The incidence of postoperative fever > 38.0 degrees C and duration of postoperative pyuria did not differ significantly between groups with or without biopsy. Preoperative biopsy did not contribute to perioperative morbidity. Tumors detected by systematic biopsy are usually large and clinically significant. Positive biopsy results are often diagnostic, but the pathological features of a tumor together with clinical parameters should be considered to reduce the chance of overdiagnosing an insignificant tumor. Sextant biopsy would be most applicable to patients scheduled for any type of therapy other than TURP especially in those with markedly elevated serum PSA levels. This procedure may be beneficial particularly for younger patients with long life expectancy who will benefit from definitive therapy.

Aged↗
PubMedDate not supplied

Twenty-year follow-up of the breast cancers diagnosed during the Breast Cancer Detection Demonstration Project.

This study reports on the 20-year follow-up of the women diagnosed with breast cancer in the Breast Cancer Detection Demonstration Project (BCDDP) between 1973 and 1980. This project provided 5 years of screening with physical examination and two-view mammography for 280,000 volunteer women across the United States. Based on a 96% follow-up from 1993 to 1995 of the 4,051 women with breast cancer available for analysis, 2,658 (66%) were alive and 1,393 (34%) were dead. A high proportion of the cancers were detected by mammography alone, and 28.6% of all the cancers were smaller than 1.0 cm. Survival rates were calculated by life table method with deaths from breast cancer as the outcome. The adjusted survival rate for the entire group was 80.5%, and the observed survival rate was 61.7%. Adjusted and observed survival rates were 97.2% and 78.5%, respectively, for women with non-invasive cancers and 78.2% and 59.3%, respectively, for those with invasive cancers. Lymph node status and the size of the cancer at diagnosis were prognostic indicators of survival in the BCDDP Women with invasive cancers and negative lymph nodes had an 85.5% breast cancer survival rate and a 65.6% observed survival rate. Adjusted survival rates for women with invasive breast cancers were 90.2% for cancers smaller than 1 cm, 80.5%, for cancers 1.0 to 1.9 cm, 70.5% for cancers 2.0 to 4.9 cm, and 60.6% for cancers larger than 5 cm. Women 40 to 49 years of age demonstrated a greater survival with noninvasive or invasive cancers smaller than 5.0 cm compared with women 50 to 59 and 60 to 69 years of age at diagnosis. These results from the BCDDP are discussed in the context of the recent decline in breast cancer incidence and mortality in the United States.

Adult↗
PubMed2026

Non-invasive strategy for gastric cancer detection: Integration of cell-free DNA fragmentomics and protein biomarkers.

Gastric cancer (GC) ranks as the fifth most common cancer worldwide, however, accurate and non-invasive diagnostic modalities for GC remain limited. Cell-free DNA (cfDNA) fragmentomics has emerged as a promising tool for cancer cell detection. Here we develop a gastric cancer detection model, named GaFraD model. The GaFraD model uses four cfDNA fragmentomics features, including fragment size ratio (FSR), copy number variation (CNV), 9-bp end motif (Motif), and fragment size at transcription start sites (TF). This model achieves an area under the receiver-operating characteristic curve (AUC) of 0.970 (95% CI: 0.944 - 0.990), a sensitivity of 95.0% and a specificity of 80.9%. By combining the GaFraD model and conventional protein biomarkers CA19-9 and PG-I/PG-II, the CONFIRM model was generated. The CONFIRM model attained an AUC of 0.986 (95% CI: 0.966 - 1.000), a sensitivity of 95.0% and a specificity of 95.6% in detecting GC. Moreover, the CONFIRM model achieved remarkable performance (AUC = 0.983, sensitivity 95.6%, specificity 94.2%) in distinguishing patients with early-stage GC from controls. Our work showed the high discriminatory power in distinguishing GC patients from controls, indicating the clinical potential of using cfDNA fragmentomics combined with protein biomarkers for non-invasive GC detection. The results of the study provide a new avenue for early, accurate, and non-invasive clinical diagnosis of GC.

Cell-free DNA↗
PubMed1989

Body size and breast cancer risk assessed in women participating in the Breast Cancer Detection Demonstration Project.

In a case-control study that included 2,560 breast cancer cases and 2,679 controls, the authors examined the association between body size and breast cancer with the use of measured height and weight of white US women. The subjects were women aged 26-93 years recruited between 1973 and 1975 for participation in the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program. After controlling for the effect of potential confounders, the relative risks of breast cancer across increasing quartiles of height were 1.00, 1.07, 1.15, and 1.27 (p = 0.001, test for trend). The effect of weight independent of height was evaluated using indices of relative weight (e.g., weight/height1.5, weight/height2), and the authors identified excess weight as a risk factor for breast cancer among women who had experienced natural menopause and among women aged 50 years or older at diagnosis. Among women aged 50 years or older, for example, the relative risks of breast cancer for increasing quartiles of weight/height1.5 were 1.00, 1.04, 1.40, and 1.29 (p = 0.0006, test for trend). An inverse association between relative weight and breast cancer risk was suggested for women younger than age 50 years at diagnosis. However, the apparent protective effect of high relative weight was restricted to women with small tumors, suggesting a detection bias.

Adult↗
PubMed1996

Comparative study of the role of serum levels of p53 antigen and its tumor cell concentration in colon cancer detection.

The role of serum levels of p53 antigen in detection of colon cancer was studied in different groups of cancer and noncancer patients and was compared with the results of immunohistochemical analyses. The p53 antigen was isolated from the human serum as a cytoplasmic fraction using the recently described new type of columns for affinity chromatography, gel fiberglass columns (Zusman and Zusman, 1995). Its concentration was detected by high performance liquid chromatography. The serum level of the p53 antigen significantly increased in cancer patients (3.6 mg ml(-1)) as compared to its concentration in patients with benign tumors (1.7 mg ml(-1)) or in patients with noncancer disorders (0.49 mg ml(-1)), and this was found to be a result of higher concentration of p53 protein in tumor cells. Coefficient of correlation between cellular concentration of p53 protein and its serum level was 0.44 in noncancer lesions and 0.48 in cancer patients. Serum levels of p53 antigen was shown to be highly active either in patients with noncancer lesions or in patients with cancer (r = 0.46 and 0.51 respectively), whereas the cell determination of p53 protein was effective only among noncancer patients (r = 0.61) but not in cancer patients (r = 0.22). The findings suggests that serum determination of p53 antigen can perhaps reveal this oncoprotein already in the early stages of cancer or even predict the putative development of cancer. The possibility to use the serum-levels of p53 antigen in the follow up patients with chronic diseases and to detect transformation of these diseases into cancer, or monitoring former cancer patients in order to detect as early as possible the incidence of recurrent cancer is discussed.

Antigens, Neoplasm↗
PubMed1998

Sensitivity and specificity of computer-assisted breast cancer detection in mammography screening.

PURPOSE: To evaluate a system of computer-assisted diagnosis (CAD) in mammography. MATERIAL AND METHODS: A sample of 120 sets of two-view mammograms was examined by an expert screener, a screening radiologist, a clinical radiologist, and a CAD system. The screening and clinical radiologists examined the mammograms twice, first without and then with the help of CAD. The sample consisted of first-round screening films from a two-round population-based screening, and comprised: 32 women in whom breast cancer was detected at the first screening; 10 with cancer detected during the screening interval; 32 with cancer detected at the second screening; and 46 with normal mammograms at both screenings. RESULTS: The expert screener, the screening radiologist, the clinical radiologist, and the CAD system detected respectively 44, 41, 34 and 37 cancers. Their respective specificities were 80%, 83%, 100% and 22%. With the help of CAD, the screening radiologist detected 1 additional cancer and the clinical radiologist detected 3; their respective specificities were 80% and 100%. CONCLUSION: The sensitivity of the CAD system was satisfactory. The two radiologists helped by CAD achieved a modest increase in sensitivity with unaffected specificity. However, the CAD system by itself had a very low specificity and it needs improvement before it can be useful in mammographic screening.

Adult↗
PubMed2006

The novella approach to inform women living on low income about early breast cancer detection.

Economically disadvantaged women have a greater likelihood of later-stage breast cancer diagnosis when compared to women with higher levels of income. Later-stage diagnosis decreases the chances of survival. The purpose of this article is to describe a project whereby breast cancer survivors, living on lower incomes, created novellas (stories) using artistic media to reach their peers with a message about the importance of early breast cancer detection. The recruitment and engagement of breast cancer survivors in a 2-year community development project that used participatory, women-driven approaches are discussed, and the reciprocal learning between health care providers, community partners, and women living on low income is shared. Recommendations for health promotion practice are presented.

Adult↗
PubMed1984

Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Johns Hopkins study.

The Johns Hopkins Lung Project was designed to determine whether the addition of cytologic screening to the radiographic screening of high-risk volunteers could enhance the early detection of asymptomatic lung cancer and whether early therapeutic intervention in detected cases could significantly reduce the mortality from this disease. Male volunteers, 45 yr of age and older, who smoked at least 1 pack of cigarettes per day were recruited from the Baltimore metropolitan area. All of the 10,387 acceptable high-risk volunteers received annual chest radiographic screening. By random assignment, one half received cytologic examination of induced sputum in addition to the roentgenogram. This report describes the results of the initial screening. Compared with usual methods of clinical diagnosis, screening by both roentgenography and cytology identified a greater proportion of the lung cancer cases at an earlier stage. Screening by sputum cytology was found to improve the detection only of squamous cell carcinoma. In the dual-screen group, sputum cytology accounted for 28% of the detected cases, and resulted in 39% additional detection of lung cancer over that achieved by roentgenography. There was no corresponding decrease in prevalence. Lung cancers detected by cytology alone were found at very early stages. Although there has been an increase in average survival, much of this increase, if not all, may have resulted from lead-time and sampling bias.

Adenocarcinoma↗
PubMed2004

Improved small volume lung cancer detection with computer-aided detection: database characteristics and imaging of response to breast cancer risk reduction strategies.

Computer-aided detection (CAD) and diagnosis (CADx) of in vivo imaging studies are important tools based on bioinformatics. Currently, there are two diseases for which the United States Food and Drug Administration (FDA) has given premarket approval (PMA): the detection of signs consistent with lung cancer on chest radiographs and breast cancer on mammograms. There are systems for other diseases and other types of images under development; however, this process depends on the availability of an accurate database. The author helped in the development of the databases for such systems and management of the clinical trial that resulted in the FDA-PMA of the system that detects findings consistent with lung cancer. The characteristics of the database used will be described. Further, a woman's risk of developing breast cancer differs from those of other women. Risk can be high, average, or low. There are now pharmaceuticals that decrease the risk that women, as a group, will develop breast cancer and it has been suggested that dietary changes could have similar effects. The pharmaceutical agents, though, have some associated side effects, and it is clinically important to determine whether these agents have decreased an individual woman's risk of breast cancer. In vivo imaging biomarkers of risk and successful risk reduction are therefore sought, but the information on possible in vivo imaging biomarkers is less mature than activities in CAD. Bioinformatics will be an important contributor to this in vivo imaging biomarker development.

Breast Neoplasms↗
PubMed1980

ACS/NCI Breast Cancer Detection Demonstration Projects.

The 28 Centers involved in the Breast Cancer Detection Demonstration Projects were initiated in 1973. The five-year commitment of some of the Projects will be completed during this calendar year, and those of others as late as 1981. The material available to us from the group of women studies is useful, but the accumulation of these data through the computer is still painfully slow. The last completed data available from the computer are those compiled through February 1979. They showed 273,108 women having completed their first examination, and the total number of examinations--1,011,709. In the breast biopsies that have been performed on patients from the study group, 85% have shown benign lesions, 14% have revealed invasive carcinoma, and 1% have shown preinvasive carcinoma, so-called carcinoma in situ. In general, these tumors have been at very early biological stages in the development of breast cancers. Some slightly less impressive figures have been obtained in those individuals who have discovered their cancers as a product of regular breast self-examination. The techniques of the survey clearly show that breast cancer can be picked up in a biologically earlier state and at a stage more amenable to definitive therapy.

Adult↗
PubMed2005

Early lung cancer detection using spiral computed tomography and positron emission tomography.

RATIONALE: Lung cancer screening using computed tomography (CT) is effective in detecting lung cancer in early stages. Concerns regarding false-positive rates and unnecessary invasive procedures have been raised. OBJECTIVE: To study the efficiency of a lung cancer protocol using spiral CT and F-18-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: High-risk individuals underwent screening with annual spiral CTs. Follow-up CTs were done for noncalcified nodules of 5 mm or greater, and FDG-PET was done for nodules 10 mm or larger or smaller (> 7 mm), growing nodules. RESULTS: A total of 911 individuals completed a baseline CT study and 424 had at least one annual follow-up study. Of the former, 14% had noncalcified nodules of 5 mm or larger, and 3.6% had nodules of 10 mm or larger. Eleven non-small cell lung cancers (NSCLC) and one small cell lung cancer (SCLC) were diagnosed in the baseline study (prevalence rate, 1.32%), and two NSCLCs in the annual study (incidence rate, 0.47%). All NSCLCs (92% of prevalence cancers) were diagnosed in stage I (12 stage IA, 1 stage IB). FDG-PET was helpful for the correct diagnosis in 19 of 25 indeterminate nodules. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET for the diagnosis of malignancy were 69, 91, 90, and 71%, respectively. However, the sensitivity and negative predictive value of the screening algorithm, which included a 3-month follow-up CT for nodules with a negative FDG-PET, was 100%. CONCLUSION: A protocol for early lung cancer detection using spiral CT and FDG-PET is useful and may minimize unnecessary invasive procedures for benign lesions.

Adult↗
PubMed1989

1H NMR of plasma for detecting cancer. The effect of trauma on linewidths.

The specificity of detecting cancer using the methyl and methylene linewidths in the 1H NMR spectrum of plasma has been examined for patients with brain tumors. Apparently healthy controls are distinguished from patients with metastatic brain tumors or malignant primary intracranial neoplasms, although the amount of overlap with the latter group precludes the use of the method as a diagnostic tool. Furthermore, patients with benign primary intracranial neoplasms are not distinguished from those with malignant primary brain tumors, and non-tumor neurological patients with traumatic head injury are not distinguished from cancer patients. Surgical treatment of neurological patients results in a significant narrowing of the 1H NMR bands of interest, particularly for patients initially exhibiting broad lines. The narrowing persists for at least 3 weeks. This effect of surgical or other trauma on the 1H NMR linewidths indicates that the method is unsuitable for assessing the efficacy of surgical treatment of cancer.

Blood Chemical Analysis↗
PubMed1988

Biostereometric analysis for breast cancer detection.

A measurement technique has been developed for noninvasive breast cancer detection. The process involves the use of close-range stereophotogrammetry as a data acquisition device for the determination of breast surface concavities. We report the methodology used to detect these surface depressions, the rationale for the study, and our preliminary findings.

Algorithms↗