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Background: Cancer screening trials have required large sample sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the "intended effect" (IE) analysis that we explain in detail herein. The IE analysis is particularly suited to tests that can be conducted on stored specimens in the control arm, such as stored blood for multicancer detection (MCD) tests., Methods: We simulated hypothetical MCD screening trials to compare power and sample size for the standard vs IE analysis. Under two assumptions that we detail herein, we projected the IE analysis for 3 existing screening trials (National Lung Screening Trial [NLST], Minnesota Colon Cancer Control Study [MINN-FOBT-A], and Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial-colorectal component [PLCO-CRC])., Results: Compared with the standard analysis for the 3 existing trials, the IE design could have reduced cancer-specific mortality P values 6-fold (NLST), 33-fold (MINN-FOBT-A), or 260 000-fold (PLCO-CRC) or, alternately, reduced sample size (90% power) by 25% (NLST), 47% (MINN-FOBT-A), or 63% (PLCO-CRC). For potential MCD trial designs requiring 100 000 subjects per arm to achieve 90% power for multicancer mortality for the standard analysis, the IE analysis achieves 90% power for only 37 500-50 000 per arm, depending on assumptions concerning control-arm test-positives., Conclusions: Testing stored specimens in the control arm of screening trials to conduct the IE analysis could substantially increase power to reduce sample size or accelerate trials and could provide particularly strong power gains for MCD tests., (Published by Oxford University Press 2024.)

Background: Cancer screening trials have required large sample sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the "intended effect" (IE) analysis that we explain in detail herein. The IE analysis is particularly suited to tests that can be conducted on stored specimens in the control arm, such as stored blood for multicancer detection (MCD) tests., Methods: We simulated hypothetical MCD screening trials to compare power and sample size for the standard vs IE analysis. Under two assumptions that we detail herein, we projected the IE analysis for 3 existing screening trials (National Lung Screening Trial [NLST], Minnesota Colon Cancer Control Study [MINN-FOBT-A], and Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial-colorectal component [PLCO-CRC])., Results: Compared with the standard analysis for the 3 existing trials, the IE design could have reduced cancer-specific mortality P values 5-fold (NLST), 33-fold (MINN-FOBT-A), or 14 160-fold (PLCO-CRC) or, alternately, reduced sample size (90% power) by 26% (NLST), 48% (MINN-FOBT-A), or 59% (PLCO-CRC). For potential MCD trial designs requiring 100 000 subjects per arm to achieve 90% power for multicancer mortality for the standard analysis, the IE analysis achieves 90% power for only 37 500-50 000 per arm, depending on assumptions concerning control-arm test-positives., Conclusions: Testing stored specimens in the control arm of screening trials to conduct the IE analysis could substantially increase power to reduce sample size or accelerate trials and could provide particularly strong power gains for MCD tests., (Published by Oxford University Press 2024.)

Answer questions and earn CME/CNE Each year, the American Cancer Society publishes a summary of its guidelines for early cancer detection, data and trends in cancer screening rates, and select issues related to cancer screening. In this issue of the journal, the authors summarize current American Cancer Society cancer screening guidelines, describe an update of their guideline for using human papillomavirus vaccination for cancer prevention, describe updates in US Preventive Services Task Force recommendations for breast and colorectal cancer screening, discuss interim findings from the UK Collaborative Trial on Ovarian Cancer Screening, and provide the latest data on utilization of cancer screening from the National Health Interview Survey. CA Cancer J Clin 2017;67:100-121. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: Population-based testing for BRCA1/2 mutations detects the high proportion of carriers not identified by cancer family history (FH)-based testing. We compared the cost-effectiveness of population-based BRCA testing with the standard FH-based approach in Ashkenazi Jewish (AJ) women., Methods: A decision-analytic model was developed to compare lifetime costs and effects amongst AJ women in the UK of BRCA founder-mutation testing amongst: 1) all women in the population age 30 years or older and 2) just those with a strong FH (≥10% mutation risk). The model assumes that BRCA carriers are offered risk-reducing salpingo-oophorectomy and annual MRI/mammography screening or risk-reducing mastectomy. Model probabilities utilize the Genetic Cancer Prediction through Population Screening trial/published literature to estimate total costs, effects in terms of quality-adjusted life-years (QALYs), cancer incidence, incremental cost-effectiveness ratio (ICER), and population impact. Costs are reported at 2010 prices. Costs/outcomes were discounted at 3.5%. We used deterministic/probabilistic sensitivity analysis (PSA) to evaluate model uncertainty., Results: Compared with FH-based testing, population-screening saved 0.090 more life-years and 0.101 more QALYs resulting in 33 days' gain in life expectancy. Population screening was found to be cost saving with a baseline-discounted ICER of -£2079/QALY. Population-based screening lowered ovarian and breast cancer incidence by 0.34% and 0.62%. Assuming 71% testing uptake, this leads to 276 fewer ovarian and 508 fewer breast cancer cases. Overall, reduction in treatment costs led to a discounted cost savings of £3.7 million. Deterministic sensitivity analysis and 94% of simulations on PSA (threshold £20000) indicated that population screening is cost-effective, compared with current NHS policy., Conclusion: Population-based screening for BRCA mutations is highly cost-effective compared with an FH-based approach in AJ women age 30 years and older., (© The Author 2014. Published by Oxford University Press.)

Objective: Identify predictors of non-compliance with first round screening exams in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial., Method: The PLCO was conducted from 1993 to 2011 at 10 US institutions. A total of 154,897 healthy men and women ages 55-74 years were randomized. Intervention arm participants were invited to receive gender-appropriate screening exams for prostate, lung, colorectal and ovarian cancer. Using intervention-arm data (73,036 participants), non-compliance percentages for 13 covariates were calculated, as were unadjusted and adjusted odds ratios (ORs), and 95% confidence intervals. Covariates included demographic factors as well as factors specific to PLCO (e.g., method of consent, distance from screening center)., Results: The rate of non-compliance was 11% overall but varied by screening center. Significant associations were observed for most covariates but indicated modest increases or decreases in odds. An exception was the use of a two-step consent process (consented intervention arm participants for exams after randomization) relative to a one-step process (consented all participants prior to randomization) (OR: 2.2, 95% CI: 2.0-2.5). Non-compliance percentages increased with further distance from screening centers, but ORs were not significantly different from 1., Conclusions: Many factors modestly influenced compliance. Consent process was the strongest predictor of compliance., (Published by Elsevier Inc.)

Despite advances in gynecologic oncology, ovarian cancer is still mostly diagnosed very late or in advanced stages, which leads to adverse outcome of the disease. The pathogenesis of this disease as well as the risk factors for its development are not completely understood, while symptoms in the early stage of disease are sometimes nonspecific and delay earlier diagnosis. The aim is to present recent knowledge about the screening and diagnosis of ovarian cancer, with sp6cial reference to the role of ultrasound in recognizing the disease and referring patients for further consultation.

The first Cochrane systematic review examining the evidence on screening for prostate cancer was first published in 2006. The 2006 version of the Cochrane review identified two randomised controlled trials (RCTs), drawing the conclusion that there was insufficient evidence to either support, or refute, the use of screening versus no screening in reducing prostate cancer-specific mortality. The most recent version of the review, published in 2013, assessed evidence from five RCTs. Based on the evidence from the five RCTs, the authors of the 2013 version concluded that screening did not significantly reduce prostate cancer-specific mortality. Of the five trials included in the 2013 Cochrane review, only two were assessed as being a low risk of bias--the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening trial. This chapter discusses the differences between the ERSPC and PLCO trials, and examines what issues may contribute to their conflicting results. It also aims to contextualise results from this most recent Cochrane systematic review and discuss the critique of the Cochrane systematic review raised by Schroder in the chapter entitled, "ERSPC, PLCO studies and critique of Cochrane review 2013".

The prostate portion of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial began in the early 1990s to assess the ability of annual PSA and DRE to reduce prostate cancer specific mortality in men aged 55-74. Approximately 80,000 men have been randomized and followed for a minimum of 13 years. Thus far, annual screening in this study has not been associated with a reduction of prostate cancer specific mortality. The potential explanations for this finding are reviewed.

Screening for prostate cancer by use of serum prostate specific antigen (PSA) remains controversial. In the recent Cochrane analysis, an attempt is made to clarify the issue by conducting a meta analysis of available randomized screening trials. Two large trials are considered to provide data of similar and sufficient quality to conduct a separate meta analysis. However, in the view of this author, this analysis fails because standard Cochrand quality criteria are not observed. Details are given and the outcome suggests that one of the trials, the European Randomized Study of Screening for Prostate Cancer (ERSPC) should be considered superior to the Prostate, Lung, Colon, Ovary screening trial (PLCO) conducted in the USA.

The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial is a large-scale research effort conducted by the National Cancer Institute. PLCO offers an example of coordinated research by both the extramural and intramural communities of the National Institutes of Health. The purpose of this article is to describe the PLCO research resource and how it is managed and to assess the productivity and the costs associated with this resource. Such an in-depth analysis of a single large-scale project can shed light on questions such as how large-scale projects should be managed, what metrics should be used to assess productivity, and how costs can be compared with productivity metrics. A comprehensive publication analysis identified 335 primary research publications resulting from research using PLCO data and biospecimens from 2000 to 2012. By the end of 2012, a total of 9679 citations (excluding self-citations) have resulted from this body of research publications, with an average of 29.7 citations per article, and an h index of 45, which is comparable with other large-scale studies, such as the Nurses' Health Study. In terms of impact on public health, PLCO trial results have been used by the US Preventive Services Task Force in making recommendations concerning prostate and ovarian cancer screening. The overall cost of PLCO was $454 million over 20 years, adjusted to 2011 dollars, with approximately $37 million for the collection, processing, and storage of biospecimens, including blood samples, buccal cells, and pathology tissues.

Objective: One risk management strategy that women at increased familial risk of ovarian cancer may use is screening. Until recently, this has been available as part of the UK Familial Ovarian Cancer Screening Study (UKFOCSS), using ultrasound scans of the ovaries and tumour marker blood tests. The present study aimed to gain an in-depth understanding of women's experiences of participating in ovarian cancer screening., Methods: Semi-structured interviews were conducted with 48 UKFOCSS participants. Interviews were recorded, transcribed and relevant sections analysed using a framework approach., Results: Screening provided women with reassurance which they found beneficial. A sense of privilege, as well as feeling proactive in potentially detecting ovarian cancer at an early stage was described. The wider benefit to research and the potential impact this could have on others was also important to women. Negative experiences of screening included worry about the screening tests and results, false reassurance by test results and disappointment with ineffective screening. Aspects of the screening study, such as the logistics, organisation and communication, were described as both good and problematic. When weighed up by the women, most described an overall positive experience of screening., Conclusions: Women reported both positive and negative experiences of screening. Overall, screening seemed to be an acceptable risk management strategy to most women who participated in this interview study. Improvements could be made particularly in helping women to understand the limitations of familial ovarian cancer screening in order to avoid false reassurance., (Copyright © 2013 John Wiley & Sons, Ltd.)

Outcomes after genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome have not been well studied in underserved populations. We surveyed 1,123 BRCA testers from a genetic counseling program serving an academic cancer center (n=1,045) and a public county hospital (n=78) a median of 3.7 years after testing for mutations in BRCA1 and BRCA2 (breast cancer susceptibility genes). We compared genetic counseling outcomes, cancer screening rates, and self-reported general health. We found no differences in genetic counseling outcomes between hospitals. Breast cancer screening rates were similarly high at both hospitals, which are warranted in this high-risk population. Screening rates for ovarian, colon, and skin cancer were significantly lower in participants from the public hospital. BRCA results were not a predictor of general health at either hospital. When creating a genetic counseling program that serves women in different hospital settings, providers should emphasize guidelines-based screening recommendations for all patients.

Purpose: Obesity has consistently been linked to an increased risk of colorectal cancer, particularly among men. Whether body mass index (BMI) differentially influences the risk across the stages of colorectal cancer development remains unclear. We evaluated the associations of BMI with colorectal adenoma incidence, adenoma recurrence, and cancer in the context of a large screening trial, in which cases and controls had an equal chance for disease detection., Methods: We prospectively evaluated the association between baseline BMI and the risk of incident distal adenoma (1,213 cases), recurrent adenoma (752 cases), and incident colorectal cancer (966 cases) among men and women, ages 55 to 74 years, randomly assigned to receive flexible sigmoidoscopy screening as part of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We calculated odds ratios (ORs) and 95% CIs for adenoma incidence and recurrence, and hazard ratios (HRs) and 95% CIs for colorectal cancer incidence, using multivariable-adjusted models., Results: Compared with normal-weight men (18.5 to 24.9 kg/m(2)), obese men (≥ 30 kg/m(2)) had significantly higher risk of incident adenoma (OR, 1.32; 95% CI, 1.06 to 1.65) and colorectal cancer (HR, 1.48; 95% CI, 1.16 to 1.89) and a borderline increased risk of recurrent adenoma (OR, 1.50; 95% CI, 0.98 to 2.30). No associations were observed for either adenoma or cancer in women., Conclusion: Data from this large prospective study suggest that obesity is important throughout the natural history of colorectal cancer, at least in men, and colorectal cancer prevention efforts should encourage the achievement and maintenance of a healthy body weight in addition to regular screenings.

Background: For women at potentially increased risk for ovarian cancer, data regarding screening and risk reduction are limited. Previous studies have reported on the behaviors of BRCA mutation carriers, but less is known about the behaviors of non- BRCA carriers. We surveyed a large cohort of women after BRCA testing to identify the prevalence and posttest predictors of risk-reducing and screening interventions., Methods: A median of 3.7 years after BRCA testing, 1447 women who received genetic counseling and BRCA testing at 2 hospital sites were surveyed, with a 77.6% response rate. We analyzed data from 1077 survey respondents. We performed univariate and multivariate logistic regression analyses to identify predictors of risk-reducing salpingo-oophorectomy (RRSO), screening transvaginal ultrasonography (TVUS), and screening serum cancer antigen 125 (CA-125)., Results: Among the respondents, 201 women (18.7%) received positive test results for a deleterious mutation, 103 women (9.6%) received true-negative results, and 773 women (71.8%) received uninformative results. Overall, 19.1% of eligible women underwent RRSO and 39.6% used screening procedures. A positive BRCA result predicted RRSO (odds ratio [OR], 28.1; 95% CI, 16.2-48.6), TVUS (9.5 [4.3-21.0]), and serum CA-125 (13.0 [5.5-29.0]). Similarly, a true-negative BRCA result reduced the OR for RRSO (0.1 [0.0-0.6]), TVUS (0.2 [0.1-0.5]), and serum CA-125 (0.3 [0.1-0.7]). Of the 71.8% of women who received uninformative results after BRCA testing, 12.3% subsequently underwent RRSO, 33.8% reported ever having undergone screening serum CA-125 since BRCA testing, and 37.3% reported ever having undergone screening TVUS since BRCA testing., Conclusions: Results of BRCA testing strongly predict RRSO and ovarian cancer screening. Use of RRSO and ovarian screening was reported in a sizable percentage of non- BRCA carriers despite insufficient data to determine the effectiveness of these interventions.

Purpose: To establish the performance characteristics of annual transvaginal ultrasound and serum CA125 screening for women at high risk of ovarian/fallopian tube cancer (OC/FTC) and to investigate the impact of delayed screening interval and surgical intervention., Patients and Methods: Between May 6, 2002, and January 5, 2008, 3,563 women at an estimated ≥ 10% lifetime risk of OC/FTC were recruited and screened by 37 centers in the United Kingdom. Participants were observed prospectively by centers, questionnaire, and national cancer registries., Results: Sensitivity for detection of incident OC/FTC at 1 year after last annual screen was 81.3% (95% CI, 54.3% to 96.0%) if occult cancers were classified as false negatives and 87.5% (95% CI, 61.7% to 98.5%) if they were classified as true positives. Positive and negative predictive values of incident screening were 25.5% (95% CI, 14.3 to 40.0) and 99.9% (95% CI, 99.8 to 100) respectively. Four (30.8%) of 13 incident screen-detected OC/FTCs were stage I or II. Compared with women screened in the year before diagnosis, those not screened in the year before diagnosis were more likely to have ≥ stage IIIc disease (85.7% v 26.1%; P = .009). Screening interval was delayed by a median of 88 days before detection of incident OC/FTC. Median interval from detection screen to surgical intervention was 79 days in prevalent and incident OC/FTC., Conclusion: These results in the high-risk population highlight the need for strict adherence to screening schedule. Screening more frequently than annually with prompt surgical intervention seems to offer a better chance of early-stage detection.

The Austrian guideline for prevention and early detection of breast and ovarian cancer in high risk patients--particularly in women from hereditary breast and ovarian cancer families--were established with particular consideration of the most recent position paper of the European Society of Breast Cancer Specialists (EUSOMA) by the authors mentioned above. The guideline is aimed at facilitating and standardizing the care and early detection strategies in women with an elevated life time risk for breast and ovarian cancer.

Advances in screening and early detection of ovarian cancer over the past decade have included novel interpretation of serum CA125, discovery of human epididymis protein 4, which has the potential to add to CA125, and the growing understanding of the flaws of previous biomarker studies. No mortality effect was found in the ovarian screening arm of the Prostate Lung Colorectal and Ovarian Cancer Screening Trial.(87) Concerns, however, have been raised about trial design, and the results from the UK Collaborative Trial of Ovarian Cancer Screening in the general population(38) and other ongoing studies in the high-risk population are awaited for a definitive conclusion. Future work needs to take into account the new insights into ovarian cancer subtypes and the growing evidence that a significant proportion of ovarian cancers might originate in premalignant lesions in the distal fallopian tube., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Annual screening of asymptomatic postmenopausal women using a combination of transvaginal sonography and serum Ca-125 has been evaluated in 4 major clinical trials as a means to facilitate earlier detection of ovarian cancer. In several trials, screening has caused a decrease in stage at detection. These ovarian cancer screening trials are reviewed. The effect of screening on ovarian cancer mortality varies in different trials and is the subject of further investigation.

Background: In Norway, mass examination for cervical cancer was started in 1995 with the goal to reduce incidence and mortality through rational use of resources. This has been successful. We wished to assess the knowledge base for this practice, as well as that on usefulness of mass examination for ovarian cancer and uterine body cancer., Material and Method: This article is based on literature identified through a non-systematic search in PubMed., Results: Despite knowledge of several risk factors for uterine body cancer, there is not sufficient evidence to support mass examination for this condition. Within a few years it will become clear whether large ongoing studies provide sufficient evidence to recommend screening for ovarian cancer. The effect of mass examination for cervical cancer is well documented., Interpretation: Cervical cancer is the only gynecological condition with an established mass examination program. This program must be adapted to new methods and the population's vaccine status in the coming years. There is not sufficient documentation on ovarian cancer or uterine body cancer to support mass examination, but this may change during a few years.

Background: Participants in trials evaluating preventive interventions such as screening are on average healthier than the general population. To decrease this 'healthy volunteer effect' (HVE) women were randomly invited from population registers to participate in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and not allowed to self refer. This report assesses the extent of the HVE still prevalent in UKCTOCS and considers how certain shortfalls in mortality and incidence can be related to differences in socioeconomic status., Methods: Between 2001 and 2005, 202 638 postmenopausal women joined the trial out of 1 243 312 women randomly invited from local health authority registers. The cohort was flagged for deaths and cancer registrations and mean follow up at censoring was 5.55 years for mortality, and 2.58 years for cancer incidence. Overall and cause-specific Standardised Mortality Ratios (SMRs) and Standardised Incidence Ratios (SIRs) were calculated based on national mortality (2005) and cancer incidence (2006) statistics. The Index of Multiple Deprivation (IMD 2007) was used to assess the link between socioeconomic status and mortality/cancer incidence, and differences between the invited and recruited populations., Results: The SMR for all trial participants was 37%. By subgroup, the SMRs were higher for: younger age groups, extremes of BMI distribution and with each increasing year in trial. There was a clear trend between lower socioeconomic status and increased mortality but less pronounced with incidence. While the invited population had higher mean IMD scores (more deprived) than the national average, those who joined the trial were less deprived., Conclusions: Recruitment to screening trials through invitation from population registers does not prevent a pronounced HVE on mortality. The impact on cancer incidence is much smaller. Similar shortfalls can be expected in other screening RCTs and it maybe prudent to use the various mortality and incidence rates presented as guides for calculating event rates and power in RCTs involving women.

Routine pelvic examinations are the core of the periodic gynecological examination and widely tolerated as a necessary part of health maintenance. Is this examination beneficial for asymptomatic women? Justifications for the pelvic examination include screening for Chlamydia (or gonorrhea) infection, evaluation before initiation of hormonal contraception, screening for cervical cancer, and early detection of ovarian cancer. Current nucleic acid amplification tests for Chlamydia and gonorrhea permit the use of urine and self-administered vaginal swabs, which most women prefer over a pelvic examination. Pelvic examination findings do not affect the decision to prescribe or withhold systemic hormonal contraception; a pelvic examination is not needed to initiate these contraceptives. Recent American College of Obstetricians and Gynecologists (ACOG) guidelines recommend less frequent cervical screening, thus decreasing the frequency of a speculum examination for cervical screening. Bimanual examinations for palpation of the uterus and ovaries are also routinely performed in the United States. Clinical trial data, however, show these examinations do not lead to earlier detection of ovarian cancer. No evidence identifies benefits of a pelvic examination in the early diagnosis of other conditions in the asymptomatic woman. Speculum and bimanual examinations are uncomfortable, disliked by many women, and use scarce time during a well woman visit. Eliminating the speculum examination from most visits and the bimanual examination from all visits of asymptomatic women will free resources to provide services of proven benefit. Overuse of the pelvic examination contributes to high healthcare costs without any compensatory health benefit.

Prevention has potential benefits, but the majority of people undergoing disease screening will receive no benefit and may actually be exposed to health risks. Public opinion is generally very favorable toward prevention. However, many recent guidelines recommend fewer preventive services in women than previously suggested. New recommendations are to wait until 50 for mammography screening, to screen only every other year, and to not teach self breast examinations. Papanicolaou tests for cervical cancer screening are recommended to be done less often (every 2-3 years) and to be started later than previously suggested (not before age 21). Screening for ovarian cancer is not recommended. Guidelines suggest avoiding hormone therapy for primary prevention of coronary heart disease, not giving aspirin to prevent myocardial infarctions in women, and not screening women without risk factors for hyperlipidemia. These recommendations have caused confusion and, because of being revealed during a national health reform debate, have even been perceived as "rationing care." Others see them as "rational care," because they encourage utilization of beneficial services while discouraging use of those that may lead to more harms than benefits. Development of prevention guidelines requires value judgments, so despite the use of evidence, these recommendations have not all achieved widespread support. Understanding the data behind the guidelines, health care providers can decide how to approach prevention in practice, taking into consideration individual patient risk factors and preferences.

The National Breast and Ovarian Cancer Centre position statement: 'Population screening and early detection of ovarian cancer in asymptomatic women', was developed and agreed following a Forum in February 2009 attended by key Australian stakeholders. The final position statement and supporting background information have been endorsed by key Australian colleges and agencies. Position statement on population screening and early detection of ovarian cancer in asymptomatic women: 1) There is currently no evidence that any test, including pelvic examination, CA125 or other biomarkers, ultrasound (including transvaginal ultrasound), or combination of tests, results in reduced mortality from ovarian cancer. 2) There is no evidence to support the use of any test, including pelvic examination, CA125 or other biomarkers, ultrasound (including transvaginal ultrasound), or combination of tests, for routine population-based screening for ovarian cancer. 3) Further validation in large clinical trials is required before current or new biomarkers could be recommended for routine use in a population screening setting.

Screening for ovarian cancer shows promise, but there remains a lack of awareness of the disease among health professionals and the public.

Background: Multidisciplinary attempts to understand the etiology of breast cancer are expanding to increasingly include new potential markers of disease risk. Those efforts may have maximal scientific and practical influence if new findings are placed in context of the well-understood lifestyle and reproductive risk factors or existing risk prediction models for breast cancer. We therefore evaluated known risk factors for breast cancer in a cancer screening trial that does not have breast cancer as a study endpoint but is large enough to provide numerous analytic opportunities for breast cancer., Methods: We evaluated risk factors for breast cancer (N = 2085) among 70,575 women who were randomized in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Using Poisson regression, we calculated adjusted relative risks [RRs, with 95% confidence intervals (CIs)] for lifestyle and reproductive factors during an average of 5 years of follow-up from date of randomization., Results: As expected, increasing age, nulliparity, positive family history of breast cancer, and use of menopausal hormone therapy were positively associated with breast cancer. Later age at menarche (16 years or older vs. < 12: RR = 0.81, 95% CI, 0.65-1.02) or menopause (55 years or older vs. < 45: RR = 1.29, 95% CI, 1.03-1.62) were less strongly associated with breast cancer than was expected. There were weak positive associations between taller height and heavier weight, and only severe obesity [body mass index (BMI; kg/m(2)) 35 or more vs. 18.5-24.9: RR = 1.21, 95% CI, 1.02-1.43] was statistically significantly associated with breast cancer., Conclusion: The ongoing PLCO trial offers continued opportunities for new breast cancer investigations, but these analyses suggest that the associations between breast cancer and age at menarche, age at menopause, and obesity might be changing as the underlying demographics of these factors change., Clinical Trials Registration: (http://www.clinicaltrials.gov), NCT00002540.

Background: The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) is a US National Cancer Institute (NCI)-funded randomized controlled trial designed to evaluate whether certain screening tests reduce mortality from prostate, lung, colorectal, and ovarian cancer. To obtain adequate statistical power, it was necessary to enroll over 150,000 healthy volunteers. Recruitment began in 1993 and ended in 2001., Purpose: Our goal is to evaluate the success of recruitment methods employed by the 10 PLCO screening centers. We also provide estimates of recruitment yield and cost for our most successful strategy, direct mail., Methods: Each screening center selected its own methods of recruitment. Methods changed throughout the recruitment period as needed. For this manuscript, representatives from each screening center provided information on methods utilized and their success., Results: In the United States between 1993 and 2001, ten screening centers enrolled 154,934 study participants. Based on participant self-report, an estimated 95% of individuals were recruited by direct mail. Overall, enrollment yield for direct mail was 1.0%. Individual center enrollment yield ranged from 0.7% to 3.8%. Cost per enrolled participant was $9.64-35.38 for direct mail, excluding personnel costs., Limitations: Numeric data on recruitment processes were not kept consistently at individual screening centers. Numeric data in this manuscript are based on the experiences of 5 of the 10 centers., Conclusions: Direct mail, using rosters of names and addresses from profit and not-for-profit (including government) organizations, was the most successful and most often used recruitment method. Other recruitment strategies, such as community outreach and use of mass media, can be an important adjunct to direct mail in recruiting minority populations.

Objective: To describe the factors that contributed to successful recruitment of more than 200,000 women to the UK Collaborative Trial of Ovarian Cancer Screening, one of the largest ever randomised controlled trials., Design: Descriptive study., Setting: 13 NHS trusts in England, Wales, and Northern Ireland., Participants: Postmenopausal women aged 50-74; exclusion criteria included ovarian malignancy, bilateral oophorectomy, increased risk of familial ovarian cancer, active non-ovarian malignancy, and participation in other ovarian cancer screening trials., Main Outcome Measures: Achievement of target recruitment, acceptance rates of invitation, and recruitment rates., Results: The trial was set up in 13 centres with 27 adjoining local health authorities. The coordinating centre team was led by one of the senior investigators, who was closely involved in planning and day to day trial management. Of 1 243,282 women invited, 23.2% (288 955) replied that they were eligible and would like to participate. Of those sent appointments, 73.6% (205 090) attended for recruitment. The acceptance rate varied from 19% to 33% between trial centres. Measures to ensure target recruitment included named coordinating centre staff supporting and monitoring each centre, prompt identification and resolution of logistic problems, varying the volume of invitations by centre, using local non-attendance rates to determine the size of recruitment clinics, and organising large ad hoc clinics supported by coordinating centre staff. The trial randomised 202,638 women in 4.3 years., Conclusions: Planning and trial management are as important as trial design and require equal attention from senior investigators. Successful recruitment needs constant monitoring by a committed proactive management team that is willing to explore individual solutions for different centres and use central resources to improve local recruitment. Automation of trial processes with web based trial management systems is crucial in large multicentre randomised controlled trials. Recruitment can be further enhanced by using information videos and group discussions. Trial registration Current Controlled Trials ISRCTN22488978.

Objective: Recruitment of healthy subjects to long-term randomized controlled trials (RCTs) of cancer prevention or early detection has proven to be a difficult task. To quantify recruitment yield as well as characteristics of successfully recruited participants, we examined recruitment outcomes at 1 of the 10 centers participating in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, a National Cancer Institute-funded RCT of cancer screening modalities., Materials and Methods: During the early recruitment phase of PLCO (1993-1997), data on recruitment outcome were collected at the Henry Ford Health System (HFHS) in Detroit, Michigan. In this phase, HFHS identified potential participants using patient databases. Records were used to assess recruitment success by age, sex, race, household income (using area-based U.S. Census data), and preexisting morbidity. Logistic regression was used to assess whether enrollment success differed significantly according to these factors., Results: Of 74,139 persons ages 55 to 74 invited by HFHS to participate, 8,250 (11%) ;enrolled. In multivariate analyses, the odds of enrolling were modestly but significantly higher for women, Caucasians, persons in their 60's, and persons living in census blocks with higher median household income. Persons with two or more preexisting morbidities had significantly lower odds of enrolling compared to those with one or no preexisting morbidities., Conclusions: These data suggest that only a small fraction of persons invited to enroll in long-term RCTs of cancer screening modalities actually do so. In this urban, Midwestern setting, certain characteristics including age, race, and income influenced recruitment success, albeit modestly.

Women who have documented BRCA1 or BRCA2 mutations have a significantly increased lifetime risk of ovarian and breast malignancies. Many women, however, have a perceived personal risk of ovarian cancer despite a calculated low risk, and some seek ways to reduce the risk for ovarian cancer. Given the low prevalence of ovarian cancer in the general population, no screening test has achieved satisfactory levels of disease prediction. This article discusses the efficacy of available screening modalities and reviews current risk-reduction strategies and their effectiveness for preventing ovarian cancer.

Background: Ovarian cancer has the highest mortality rate of all gynecologic malignancies, and most women present with advanced-stage disease. The current investigation was performed to determine the efficacy of annual transvaginal sonography (TVS) as a screening method for ovarian cancer., Methods: Annual TVS screening was performed on 25,327 women from 1987 to 2005. Asymptomatic women aged>or=50 years and women aged>or=25 years who had a family history of ovarian cancer were eligible for participation in this trial., Results: Among 364 patients (1.4%) with a persisting ovarian tumor on TVS who underwent exploratory laparoscopy or laparotomy with tumor removal, 35 primary invasive ovarian cancers, 9 serous ovarian tumors of low malignant potential, and 7 cancers metastatic to the ovary were detected. Stage distribution was as follows: 28 patients had stage I disease, 8 patients had stage II disease, and 8 patients had stage III disease. Four patients died of disease, 2 patients died of other causes, and 38 patients were alive and well from 0.5 years to 15.8 years after diagnosis (mean, 5.3 years). Nine women developed ovarian cancer within 12 months of a negative screen (false-negative results), and 3 of these patients died of disease. TVS screening had a sensitivity of 85.0%, specificity of 98.7%, positive predictive value of 14.01%, and negative predictive value of 99.9%. After 107,276 screening years, there have been 7 ovarian cancer deaths in the annually screened population and 3 ovarian cancer deaths among women who were noncompliant. Excluding patients with nonepithelial or borderline ovarian malignancies, the survival of patients with ovarian cancer in the annually screened population was 89.9%+/-10.1% at 2 years and 77.2%+/-22.8% at 5 years., Conclusions: TVS screening, when it was performed annually, was associated with a decrease in disease stage at detection and with case-specific ovarian cancer mortality, but it was not effective in detecting ovarian cancers in women who had normal ovarian volume., (Copyright (c) 2007 American Cancer Society)

Objective: The national guidelines recommend more intensive screening for breast cancer for women with a family history of breast or ovarian cancer. Using the data from the 2000 National Health Interview Survey (NHIS), we examined factors related to the underuse of mammogram in this population., Method: The study subjects were 1,215 women aged 30-79 who had a family history of breast or ovarian cancer in their first-degree relatives. According to the American Cancer Society's guidelines for breast cancer screening, having no mammogram in last year was used as an outcome for this study. Socio-demographic characteristics, health-related conditions, lifestyle factors, health behaviors, menstrual/reproductive information and health care access and utilization were analyzed to assess their relations to mammogram underuse using unconditional logistic regression method., Results: The results showed that younger age, having no place to go when sick (OR = 2.2, 95% CI, 1.2-4.0), having no visits to a general doctor (OR = 1.7, 95% CI, 1.2-2.4) or medical specialist (OR = 2.2, 95% CI, 1.6-3.1) and having no influenza shot in last year (OR = 1.7, 95% CI, 1.2-2.3) increased the risk of underusing mammography screening among women who had a family history of breast or ovarian cancer. Women who had no home care from health professionals in the last year were less likely to underuse mammogram with an OR of 0.3 (95% CI, 0.1-0.6), compared with women who had., Conclusion: Medical care-related factors may affect the use of mammography screening in women with a family history of breast or ovarian cancer.

Purpose/objectives: To examine breast and ovarian cancer screening and risk-reducing behaviors of women seeking genetic cancer risk assessment (GCRA)., Design: Descriptive, cross-sectional., Setting: An insurance-based clinic that serves high-risk patients in a southern California cancer center., Sample: 134 women with breast or ovarian cancer (affected group) and 80 women with a family history of breast or ovarian cancer (unaffected group). The mean age of the sample was 48 years (range = 21-86), 79% were Caucasian, 66% were married, 60% were college educated, and 78% had children. Most affected women had early-stage disease. Unaffected women had a family history of breast (86%) or ovarian (14%) cancer., Methods: Mailed surveys assessed pre-GCRA health behaviors and health and family histories., Main Research Variables: Breast cancer screening (mammograms, clinical breast examination [CBE], breast self-examination), ovarian cancer screening (CA-125, pelvic ultrasound), and breast and ovarian cancer risk-reducing strategies (tamoxifen, bilateral mastectomy, oral contraceptive pills, bilateral salpingo-oophorectomy)., Findings: Twenty-one percent of the women who should have been having a mammogram had not had an annual examination as recommended, and 30% of affected women had not had annual CBEs. Few women took tamoxifen or oral contraceptive pills or had a bilateral salpingo-oophorectomy or bilateral mastectomy for cancer risk reduction. Twelve percent likely had unnecessary ovarian cancer screening. About 35% used other means, including herbs and homeopathy, for cancer prevention., Conclusions: Nearly a third of the affected women had not had appropriate breast cancer screening. About 12% used unsubstantiated, potentially harmful cancer "prevention" measures (e.g., herbs)., Implications for Nursing: Nurses should assess clients' personal and family breast and ovarian cancer histories and promote cancer screening and risk-reducing behaviors that are appropriate for age and risk level.

Data are presented on screening for cervical (CC), endometrial (UC) and ovarian (OC) carcinoma carried out in the Republic of Belarus as well as a discussion of logistic and methodologic aspects of the problem. Local "centers for prevention and early diagnosis of reproductive organ tumors" form the backbone of the national system. They operate on the basis of the existing guidelines about such matters as screening staging, sites, examination procedures used at each stage and suitable distribution of medical personnel (obstetricians, doctor's assistants, gynecologists). A comparison of data on selective screening for CC, UC and OC with those of mass prophylactic examinations and cytological screening for CC showed that selective detection rates for cervical dysplasia were 14 times, and in situ cervical carcinoma--4 times higher. That was followed by lower incidence of invasive CC and absence of advanced cases. Consequently, the share of endometrial hyperplasia cases rose 3.5-fold, uterine myoma--3-fold and adenomyosoma--1.5-fold. identified atypical endometrial hyperplasia, in situ cancer and endometrial stage I in "clinically healthy" women. The rates of detection of such tumor-like ovarian formations as follicular, lutein, endometrioid and para-ovarian cysts increased 2.3-fold, benign tumors--2.2-fold and polycystosis--twofold.

Purpose: The purpose of this study is to describe the factors associated with the decisions of older African American women to join the PLCO (Prostate, Lung, Colorectal and Ovarian) Cancer Screening Trial when recruited., Methods: African American women between ages 55 and 74 years who were never diagnosed with a PLCO cancer were eligible for our study. Two methods of recruitment were used. First, mailings were sent to a random sample of women describing the PLCO followed by a telephone call to determine interest in the PLCO. If women were not interested in PLCO but consented to participate in our study, they were interviewed immediately. Second, we followed up with African American women who responded to mass mailings sent out before the start of our study by the Pittsburgh PLCO office. Women completed an interview about their cancer and clinical trial knowledge, attitudes, beliefs, and behaviors. The responses of women who joined the PLCO Trial are contrasted with the responses of women who did not join., Results: Numerous factors were associated with the decision of older African American women to join the PLCO, including perceptions of cancer prevention and detection, the experience of having a loved one with cancer, knowledge of and experience with clinical trials, and beliefs regarding the benefits and risks of clinical trial participation., Conclusion: Minority recruitment to cancer clinical trials could be increased by designing interventions focused on individual, organizational, and community needs.

For the diagnosis and differential diagnosis of malignant tumors of the ovaries, transvaginal ultrasound is currently the preferred method. Ultrasound is indispensable for the pre-operative assessment of the biological significance of an ovarian tumor. With its aid,the indication for a surgical procedure can be established with a high degree of sensitivity and specificity and, where appropriate, the therapeutic approach definitively established. A further important application is screening for the early detection of an ovarian cancer. Although a high level of sensitivity and specificity can also be achieved for such an indication, an otherwise desirable screening procedure--at least in high-risk groups and post-menopausal women--is nevertheless controversial on account of the low prevalence of ovarian carcinoma and the associated poor positive predictive value (PPV).

Aim: To determine whether introducing three-dimensional (3D) ultrasonography with power Doppler facilities as a secondary screening test, preceded by annual transvaginal grayscale ultrasonography (TVUS) (followed by transvaginal color Doppler (TVCD) in selected cases) as a primary screening test for ovarian cancer improves the accuracy of ovarian cancer screening studies., Methods: Annual TVUS was performed on 3,201 peri- and postmenopausal asymptomatic women aged > or =50 years from March 1, 2001 to June 30, 2003. Cystic ovarian lesions in perimenopausal women were routinely reevaluated by TVUS and TVCD at 4-6 week intervals to avoid unnecessary surgical intervention for physiological cysts. Any multiloculated, complex or solid ovarian mass, as well as persistently cystic mass >5 cm in diameter, in which the echo architecture and/or blood flow pattern was not highly suggestive of a benign histology, was categorized malignant. In these cases, TVUS and TVCD findings were obtained in no more than 2 weeks and supplemented by secondary screening, including 3D ultrasonography, and 3D power Doppler, in combination with serum CA 125 determination. After detailed ultrasonographic examination, surgical removal of the tumor and pathohistological classification were completed., Results: Twenty-five patients (0.8%) with persisting ultrasonographic abnormalities after primary and secondary screening underwent surgery to remove the ovarian tumor. Five epithelial ovarian cancers were detected: 3 stage IA, 1 stage IB, and 1 stage IC. Three stage I patients had a palpable abnormality on clinical examination. Furthermore, in three patients with stage I disease, CA 125 serum value was elevated (> or =35 U/mL). Three-dimensional ultrasonography and power Doppler, as well as TVUS findings were indicative of malignancy in all 5 patients with stage I ovarian cancer, whereas TVCD finding was false-negative in 2 patients with stage I disease. Screening test (primary+secondary screening) had the sensitivity of 100%, specificity of 99.4%, positive predictive value of 20%, and negative predictive value of 100%., Conclusion: Application of 3D ultrasonography and power Doppler imaging in patients with "positive" standard ultrasound tests (annual TVUS, followed by TVCD in selected cases) represents a novel approach for the early and accurate detection of ovarian cancer through screening.