Screening Of High-risk Women Research Articles

Development and validation of a predictive model for postpartum endometritis.

The aim was to develop a predictive tool for anticipating postpartum endometritis occurrences and to devise strategies for prevention and control. Employing a retrospective approach, the baseline data of 200 women diagnosed with postpartum endometritis in a tertiary maternity hospital in Zhejiang Province, spanning from February 2020 to September 2022, was examined. Simultaneously, the baseline data of 1,000 women without endometritis during the same period were explored with a 1:5 ratio. Subsequently, 1,200 women were randomly allocated into a training group dataset and a test group dataset, adhering to a 7:3 split. The selection of risk factors for postpartum endometritis involved employing random forests, lasso regression, and traditional univariate and multifactor logistic regression on the training group dataset. A nomogram was then constructed based on these factors. The model's performance was assessed using the area under the curve (AUC), calculated through plotting the receiver operating characteristic (ROC) curve. Additionally, the Brier score was employed to evaluate the model with a calibration curve. To gauge the utility of the nomogram, a clinical impact curve (CIC) analysis was conducted. This comprehensive approach not only involved identifying risk factors but also included a visual representation (nomogram) and thorough evaluation metrics, ensuring a robust tool for predicting, preventing, and controlling postpartum endometritis. In the multivariate analysis, six factors were identified as being associated with the occurrence of maternal endometritis in the postpartum period. These factors include the number of negative finger tests (OR: 1.159; 95%CI: 1.091-1.233; P < 0.05), postpartum hemorrhage (1.003; 1.002-1.005; P < 0.05), pre-eclampsia (9.769; 4.64-21.155; P < 0.05), maternity methods (2.083; 1.187-3.7; P < 0.001), prenatal reproductive tract culture (2.219; 1.411-3.47; P < 0.05), and uterine exploration (0.441; 0.233-0.803; P < 0.001).A nomogram was then constructed based on these factors, and its predictive performance was assessed using the area under the curve (AUC). The results in both the training group data (AUC: 0.803) and the test group data (AUC: 0.788) demonstrated a good predictive value. The clinical impact curve (CIC) further highlighted the clinical utility of the nomogram. The development of an individualized nomogram for postpartum endometritis infection holds promise for doctors in screening high-risk women, enabling early intervention and ultimately reducing the rate of postpartum endometritis infection. This comprehensive approach, integrating key risk factors and predictive tools, enhances the potential for timely and targeted medical intervention.

Added Value of Supplemental Screening Breast MRI in Women at Average or Intermediate Breast Cancer Risk Using Abbreviated Protocols

Background: The importance of magnetic resonance imaging (MRI) screening in high-risk women is well-known; however, its utility in women at average or intermediate risk is not well-established. The main purpose of the study was to investigate the added value and cancer detection rate (CDR) of using abbreviated MRI protocols in average or intermediate-risk women. Methods: A total of 431 asymptomatic women with average or intermediate risk of breast cancer who underwent screening abbreviated MRI from May 2019 to May 2022 were recruited. CDR in screening MRI among average or intermediate-risk women and in low or high-breast composition was calculated. Results: In 173 patients with intermediate risk, 5(1.16%) malignant lesions were detected and in 258 average-risk patients, 10(2.32%) added cancers were found in screening abbreviated MRI compared to mammography. Among the 15 malignant lesions, more cancers in high breast composition were detected (11 vs. 4 cases); however, there was no statistically significant difference between the cancer detection rate and breast composition. In intermediate-risk women with high breast composition, 3 (0.69%) malignant lesions, and in average-risk women with high breast composition, 8 (1.85%) added cancers were found. Conclusion: We provided 3.48% added cancer detection in screening abbreviated MRI compared to mammography. Therefore, screening abbreviated MRI with less image acquisition and interpretation time may be useful as a supplemental screening tool for cancer detection especially in high breast composition.

Breast Cancer Screening in High-risk Women During Pregnancy and Lactation.

Women who are at high risk of developing breast cancer warrant screening that is often initiated at younger ages than in average-risk women; this is usually with a combination of annual mammography and breast MRI. Compared to average-risk women, those at high risk are more frequently recommended to undergo screening during childbearing age and thus potentially during pregnancy and lactation. Understanding the appropriate use of screening breast imaging during pregnancy and lactation can be challenging due to limited data defining the evidence-based roles of the different imaging modalities, including mammography, US, and MRI. There have also been assumptions about the diagnostic accuracy of these modalities secondary to physiological changes. This scientific review discusses the current state of evidence- and expert-based guidelines and data for breast imaging screening of high-risk pregnant and/or lactating women, and the clinical and imaging presentations of breast cancer for these women.

Research prioritisation on prevention and management of preterm birth in low and middle-income countries (LMICs) with a special focus on Bangladesh using the Child Health and Nutrition Research Initiative (CHNRI) method.

Fifteen million babies are born preterm globally each year, with 81% occurring in low- and middle-income countries (LMICs). Preterm birth complications are the leading cause of newborn deaths and significantly impact health, quality of life, and costs of health services. Improving outcomes for newborns and their families requires prioritising research for developing practical, scalable solutions, especially in low-resource settings such as Bangladesh. We aimed to identify research priorities related to preventing and managing preterm birth in LMICs for 2021-2030, with a special focus on Bangladesh. We adopted the Child Health and Nutrition Research Initiative (CHNRI) method to set research priorities for preventing and managing preterm birth. Seventy-six experts submitted 490 research questions online, which we collated into 95 unique questions and sent for scoring to all experts. A hundred and nine experts scored the questions using five pre-selected criteria: answerability, effectiveness, deliverability, maximum potential for burden reduction, and effect on equity. We calculated weighted and unweighted research priority scores and average expert agreement to generate a list of top-ranked research questions for LMICs and Bangladesh. Health systems and policy research dominated the top 20 identified priorities for LMICs, such as understanding and improving uptake of the facility and community-based Kangaroo Mother Care (KMC), promoting breastfeeding, improving referral and transport networks, evaluating the impact of the use of skilled attendants, quality improvement activities, and exploring barriers to antenatal steroid use. Several of the top 20 questions also focused on screening high-risk women or the general population of women, understanding the causes of preterm birth, or managing preterm babies with illnesses (jaundice, sepsis and retinopathy of prematurity). There was a high overlap between research priorities in LMICs and Bangladesh. This exercise, aimed at identifying priorities for preterm birth prevention and management research in LMICs, especially in Bangladesh, found research on improving the care of preterm babies to be more important in reducing the burden of preterm birth and accelerating the attainment of Sustainable Development Goal 3 target of newborn deaths, by 2030.

Abstract P5-04-01: Screening Patterns of Mammography and Breast Magnetic Resonance Imaging Following Cancer Genetic Testing in an Integrated Health Care System

Abstract Background Patients at high-risk for breast cancer with genetic mutations are recommended to receive annual breast MRI in adjunct to annual mammography. Despite 15 years of clinical guidelines, uptake of annual breast MRI remains low. Further, little is known about screening patterns across genetic test results in patients tested for hereditary cancer susceptibility as part of usual care. Methods We conducted a retrospective cohort study in an integrated health system among women aged ≥18 years old, without prior breast cancer who had genetic testing for high penetrance hereditary cancer susceptibility genes between January 1, 2010 and December 31, 2018. Genetic test orders and results (pathogenic or likely pathogenic (P/LP) variant(s), negative, or variant of uncertain significance (VUS)) were obtained from health system administrative and laboratory data. Mammogram and breast MRI use data were extracted from electronic health records and claims data. To characterize screening patterns, we calculated average proportion of time covered (PTC) as the number of days covered by mammography and/or breast MRI divided by the number of days from screening eligibility until the earliest censoring event: end of observation period, reached age 75 years, breast cancer diagnosis, death, bilateral mastectomy, or disenrollment in the health system. Per National Comprehensive Cancer Network (NCCN) guidelines, women with P/LP variants in BRCA1/2, TP53, PALB2, CHEK2, ATM, and NF1 became eligible for screening on either the day they received their genetic test result or reached age eligibility and received one year of covered time for each mammogram or MRI imaging procedure received. Per Healthcare Effectiveness Data and Information Set (HEDIS) performance measures, all other women became eligible for screening at age 50 years and received two years of covered time for each mammogram received. Average PTC was calculated overall, by genetic test results, and by screening type. Poisson regression was used to determine the association between average PTC and patient-level factors (age at test, race/ethnicity, and genetic mutations) and guideline factors (recommended screening age state). Results Of 1,167 women meeting the inclusion criteria, 140 (12%) had P/LP in high penetrance breast cancer susceptibility genes (Table 1). Average PTC for individuals with a high penetrance susceptibility gene was 34.4% for MRI, 47.6% for mammogram, 63.2% for either MRI or mammogram, and 19.0% for both screening tests. The average PTC for those who tested negative, had VUS only, and had P/LP variants in genes unrelated to breast cancer was 50.3%, 44.4%, and 40.6%, respectively. Poisson regression model showed that among those with P/LP variants in high penetrance breast cancer genes, average PTC for annual MRI was positively associated with recommended screening initiation age ≥40 years (incident rate ratio [IRR]=2.07, 95% confidence interval [CI]: 1.94-2.20), higher absolute lifetime risk of breast cancer (IRR=1.38, 95% CI: 1.31-1.49), being 40-59 years old at genetic testing (IRR=1.04, 95% CI: 1.01-1.06), and non-Hispanic White race/ethnicity (IRR=1.10, 95% CI: 1.06-1.14). Conclusions Use of breast screening in women who had a P/LP variant(s) in high penetrance breast cancer susceptibility genes was low and not consistent with clinical guidelines, but comparable to the use of screening in women with negative and VUS results. Our findings suggest the need to improve screening in high-risk women with known genetic mutations and women at average risk. Table 1. Average PTC by NCCN and HEDIS recommendation. Citation Format: Boya Guo, Sarah Knerr, Karen Wernli, Kathleen Mittendorf, Heather Feigelson, Marian Gilmore, Gail Jarvik, Tia Kauffman, Erin Keast, Beth Liles, Frances Lynch, Kristin Muessig, Sonia Sasaki, David Veenstra, Jamilyn Zepp, Ben Wilfond, Katrina Goddard, Beth Devine. Screening Patterns of Mammography and Breast Magnetic Resonance Imaging Following Cancer Genetic Testing in an Integrated Health Care System [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-04-01.

Cost-effectiveness of cervical length screening and progesterone treatment to prevent spontaneous preterm delivery in Sweden.

ABSTRACTObjectiveTo estimate the cost‐effectiveness of strategies to prevent spontaneous preterm delivery (PTD) in asymptomatic singleton pregnancies, using prevalence and healthcare cost data from the Swedish healthcare context.MethodsWe designed a decision analytic model based on the Swedish CERVIX study to estimate the cost‐effectiveness of strategies to prevent spontaneous PTD in asymptomatic women with a singleton pregnancy. The model was constructed as a combined decision‐tree model and Markov model with a time horizon of 100 years. Four preventive strategies, namely ‘Universal screening’, ‘High‐risk‐based screening’ (i.e. screening of high‐risk women only), ‘Low‐risk‐based screening’ (i.e. treatment of high‐risk population and screening of remaining women) and ‘Nullipara screening’ (i.e. treatment of high‐risk population and screening of nulliparous women only), included second‐trimester cervical length (CL) screening by transvaginal ultrasound followed by vaginal progesterone treatment in the case of a short cervix. A fifth preventive strategy involved vaginal progesterone treatment of women with previous spontaneous PTD or late miscarriage but no CL screening (‘No screening, treat high‐risk group’). For comparison, we used a sixth strategy implying no specific intervention to prevent spontaneous PTD, reflecting the current situation in Sweden (‘No screening’). Probabilities for a short cervix (CL ≤ 25 mm; base‐case) and for spontaneous PTD at < 33 + 0 weeks and at 33 + 0 to 36 + 6 weeks were derived from the CERVIX study, and probabilities for stillbirth, neonatal mortality and long‐term morbidity (cerebral palsy) from Swedish health data registers. Costs were based on Swedish data, except costs for cerebral palsy, which were based on Danish data. We assumed that vaginal progesterone reduces spontaneous PTD before 33 weeks by 30% and spontaneous PTD at 33–36 weeks by 10% (based on the literature). All analyses were from a societal perspective. We expressed the effectiveness of each strategy as gained quality‐adjusted life years (QALYs) and presented cost‐effectiveness as average (ACER; average cost per gained QALY compared with ‘No screening’) and incremental (ICER; difference in costs divided by the difference in QALYs for each of two strategies being compared) cost‐effectiveness ratios. We performed deterministic and probabilistic sensitivity analysis. The results of the latter are shown as cost‐effectiveness acceptability curves. Willingness‐to‐pay was set at a maximum of 500 000 Swedish krona (56 000 US dollars (USD)), as suggested by the Swedish National Board of Health and Welfare.ResultsAll interventions had better health outcomes than did ‘No screening’, with fewer screening‐year deaths and more lifetime QALYs. The best strategy in terms of improved health outcomes was ‘Low‐risk‐based screening’, irrespective of whether screening was performed at 18 + 0 to 20 + 6 weeks (Cx1) or at 21 + 0 to 23 + 6 weeks (Cx2). ‘Low‐risk‐based screening’ at Cx1 was cost‐effective, while ‘Low‐risk‐based screening’ at Cx2 entailed high costs compared with other alternatives. The ACERs were 2200 USD for ‘Low‐risk‐based screening’ at Cx1 and 36 800 USD for ‘Low‐risk‐based screening’ at Cx2. Cost‐effectiveness was particularly sensitive to progesterone effectiveness and to productivity loss due to sick leave during pregnancy. The probability that ‘Low‐risk‐based screening’ at Cx1 is cost‐effective compared with ‘No screening’ was 71%.ConclusionInterventions to prevent spontaneous PTD in asymptomatic women with a singleton pregnancy, including CL screening with progesterone treatment of cases with a short cervix, may be cost‐effective in Sweden. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

HUBUNGAN PARITAS TERHADAP BERAT LAHIR DI RSUD PANGERAN JAYA SUMITRA

Health development is one of the National Development efforts. The high and low infant mortality rate (IMR) is mostly influenced by low birth weight. Various efforts to improve the quality of human resources since in the womb have been carried out, one of which is by screening high-risk pregnant women. The purpose of this study was to analyze the relationship between parity and birth weight in the Balleradja room at RSUD Pangeran Jaya Sumitra.&#x0D; This study uses a quantitative research design. The study population was all postpartum mothers who were hospitalized in the Balleradja room at RSUD Pangeran Jaya Sumitra, totaling 31 people. The sample is 31 people (using total sampling technique). The research was conducted in the Balleradja room at RSUD Pangeran Jaya Sumitra. Conducted in February 2022. Data collection using a questionnaire. Data were analyzed by univariate and bivariate. Univariate analysis to present the data results into a frequency distribution table. While the bivariate analysis used the Spearman Rank correlation test with a 95% confidence level. The analytical tool in this study is SPSS 20.0.&#x0D; The results showed that there was no relationship between parity and birth weight of infants in Prince Jaya Sumitra Hospital (p value = 0.778 or p value &gt; 0.05).

Spatially tracked whole-breast three-dimensional ultrasound system toward point-of-care breast cancer screening in high-risk women with dense breasts.

Mammographic screening has reduced mortality in women through the early detection of breast cancer. However, the sensitivity for breast cancer detection is significantly reduced in women with dense breasts, in addition to being an independent risk factor. Ultrasound (US) has been proven effective in detecting small, early-stage, and invasive cancers in women with dense breasts. To develop an alternative, versatile, and cost-effective spatially tracked three-dimensional (3D) US system for whole-breast imaging. This paper describes the design, development, and validation of the spatially tracked 3DUS system, including its components for spatial tracking, multi-image registration and fusion, feasibility for whole-breast 3DUS imaging and multi-planar visualization in tissue-mimicking phantoms, and a proof-of-concept healthy volunteer study. The spatially tracked 3DUS system contains (a) a six-axis manipulator and counterbalanced stabilizer, (b) an in-house quick-release 3DUS scanner, adaptable to any commercially available US system, and removable, allowing for handheld 3DUS acquisition and two-dimensional US imaging, and (c) custom software for 3D tracking, 3DUS reconstruction, visualization, and spatial-based multi-image registration and fusion of 3DUS images for whole-breast imaging. Spatial tracking of the 3D position and orientation of the system and its joints (J1-6 ) were evaluated in a clinically accessible workspace for bedside point-of-care (POC) imaging. Multi-image registration and fusion of acquired 3DUS images were assessed with a quadrants-based protocol in tissue-mimicking phantoms and the target registration error (TRE) was quantified. Whole-breast 3DUS imaging and multi-planar visualization were evaluated with a tissue-mimicking breast phantom. Feasibility for spatially tracked whole-breast 3DUS imaging was assessed in a proof-of-concept healthy male and female volunteer study. Mean tracking errors were 0.87 ± 0.52, 0.70 ± 0.46, 0.53 ± 0.48, 0.34 ± 0.32, 0.43 ± 0.28, and 0.78 ± 0.54mm for joints J1-6 , respectively. Lookup table (LUT) corrections minimized the error in joints J1 , J2 , and J5 . Compound motions exercising all joints simultaneously resulted in a mean tracking error of 1.08 ± 0.88mm (N=20) within the overall workspace for bedside 3DUS imaging. Multi-image registration and fusion of two acquired 3DUS images resulted in a mean TRE of 1.28 ± 0.10mm. Whole-breast 3DUS imaging and multi-planar visualization in axial, sagittal, and coronal views were demonstrated with the tissue-mimicking breast phantom. The feasibility of the whole-breast 3DUS approach was demonstrated in healthy male and female volunteers. In the male volunteer, the high-resolution whole-breast 3DUS acquisition protocol was optimized without the added complexities of curvature and tissue deformations. With small post-acquisition corrections for motion, whole-breast 3DUS imaging was performed on the healthy female volunteer showing relevant anatomical structures and details. Our spatially tracked 3DUS system shows potential utility as an alternative, accurate, and feasible whole-breast approach with the capability for bedside POC imaging. Future work is focused on reducing misregistration errors due to motion and tissue deformations, to develop a robust spatially tracked whole-breast 3DUS acquisition protocol, then exploring its clinical utility for screening high-risk women with dense breasts.

Potential of NRF2 Pathway in Preventing Developmental and Reproductive Toxicity of Fine Particles.

Air pollution is associated with significant adverse health effects. Recent studies support the idea that inhalation of fine particles can instigate extrapulmonary effects on the cardiovascular system through several pathways. The systemic transfer of ultrafine particles (UFPs) or soluble particle components (organic compounds and metals) is of particular concern. An integral role of reactive oxygen species (ROS)-dependent pathways has been suggested in systemic inflammatory responses and vascular dysfunction at the molecular level. Accumulating lines of evidence suggest that fine particles affect fetal development, giving rise to low birth weight and a reduction in fetal growth, and also affect the immune, cardiovascular, and central nervous systems. Oxidative stress plays an important role in fine particles toxicity; pre-treatment with antioxidants partially suppresses the developmental toxicity of fine particles. On the other hand, Nuclear factor erythroid-derived 2-like 2 (Nfe2l2), also known as NRF2, is a transcription factor essential for inducible and/or constitutive expression of phase II and antioxidant enzymes. Studies using Nrf2-knockout mice revealed that NRF2 dysfunction is intimately involved in the pathogenesis of various human diseases. Multiple single nucleotide polymorphisms (SNPs) have been detected in human NRF2 locus. An NRF2 gene SNP (−617C > A; rs6721961), located in the upstream promoter region, affects the transcriptional level of NRF2 and thereby the protein level and downstream gene expression. It has been reported that the SNP-617 is associated with various diseases. The onset and exacerbation of the diseases are regulated by genetic predisposition and environmental factors; some people live in the air-polluted environment but are not affected and remain healthy, suggesting the presence of individual differences in the susceptibility to air pollutants. NRF2 polymorphisms may also be associated with the fetal effects of fine particles exposure. Screening high-risk pregnant women genetically susceptible to oxidative stress and prevention by antioxidant interventions to protect fetal development in air-polluted areas should be considered. This article reviews the recent advances in our understanding of the fetal health effects of fine particles and describes potential chemoprevention via the NRF2 pathway to prevent the developmental and reproductive toxicity of fine particles.

Cost-effectiveness of risk-based breast cancer screening: A systematic review.

To analyse published evidence on the economic evaluation of risk-based screening (RBS), a full systematic literature review was conducted. After a quality appraisal, we compared the cost-effectiveness of risk-based strategies (low-risk, medium-risk and high-risk) with no screening and age-based screening. Studies were also analysed for modelling, risk stratification methods, input parameters, data sources and harms and benefits. The 10 modelling papers analysed were based on screening performance of film-based mammography (FBM) (three); digital mammography (DM) and FBM (two); DM alone (three); DM, ultrasound (US) and magnetic resonance imaging (one) and DM and US (one). Seven studies did not include the cost of risk-stratification, and one did not consider the cost of diagnosis. Disutility was incorporated in only six studies (one for screening and five for diagnosis). None of the studies reported disutility of risk-stratification (being considered as high-risk). Risk-stratification methods varied from only breast density (BD) to the combination of familial risk, genetic susceptibility, lifestyle, previous biopsies, Jewish ancestry and reproductive history. Less or no screening in low-risk women and more frequent mammography screening in high-risk women was more cost-effective compared to no screening and age-based screening. High-risk women screened annually yielded a higher mortality rate reduction and more quality-adjusted life years at the expense of higher cost and false positives. RBS can be cost effective compared to the alternatives. However, heterogeneity among risk-stratification methods, input parameters, and weaknesses in the methodologies hinder the derivation of robust conclusions. Therefore, further studies are warranted to assess newer technologies and innovative risk-stratification methods.

Study of risk factors associated with breast cancer: a case control study

Background: Developing countries are facing double burden of infectious and non-communicable diseases. Omran gave epidemiological transition theory, which can be seen in India also. Lifestyle changes made Indian prone to non-communicable diseases. Cancer is among the most common non communicable diseases in India. Breast cancer contributes one fourth of all cancer burden in India. It is noted that more number of cases are being seen in 25 to 40 years age group. Objective of the study was to study risk factor associated with breast cancer.Methods: Hospital based case control study was conducted in tertiary cancer centre from July 2017 to December 2019. Sample size of 96 cases was calculated, though 100 cases was interviewed and similar number of age group matched controls was selected. Sociodemographic, past history of benign breast lesion, family history of breast cancer, body mass index, waist to hip ratio and reproductive risk factors was assessed.Results: The significant risk factors on multiple logistic regression were (adjusted odds ratios with 95% CI) age at menarche ≤11 years (1.16, 1.025–1.451), waist to hip ratio more than 0.85 (1.61, 1.473–1.963) and history of abortion (1.14, 1.006–1.366).Conclusions: Women with early age of menarche, higher waist to hip ratio and history of abortion were found to be at higher risk of developing breast cancer. Annual screening of high risk women, teaching self-breast examination to all women and promoting physical activity to maintain waist to hip ratio less than 0.85 should be done.

Lessons Learned from Setting Up a Prospective, Longitudinal, Multicenter Study with Women at High Risk for Breast Cancer.

Women identified with an increased risk of breast cancer due to mutations in cancer susceptibility genes or a familial history of breast cancer undergo tailored screening with the goal of detecting tumors earlier, when potential curative interventions are still possible. Ideally, screening would identify signs of carcinogenesis even before a tumor is detectable by imaging. This could be achieved by timely signaling of altered biomarker levels for precancerous processes in liquid biopsies. Currently, the Nipple Aspirate Fluid (NAF) and the Trial Early Serum Test BREAST cancer (TESTBREAST), both ongoing, prospective, multicenter studies, are investigating biomarkers in liquid biopsies to improve breast cancer screening in high-risk women. The NAF study focuses on changes over time in miRNA expression levels both in blood and NAF samples, whereas the TESTBREAST study analyzes changes in protein levels in blood samples at sequential interval timepoints. These within-subject changes are studied in relation to later occurrence of breast cancer using a nested case-control design. These longitudinal studies face their own challenges in execution, such as hindrances in logistics and in sample processing that were difficult to anticipate. This article offers insight into those challenges and concurrently aims to provide useful strategies for the set-up of similar studies.See related commentary by Sauter, p. 429.

Diffusion-Weighted Magnetic Resonance Imaging for Breast Cancer Screening in High-Risk Women: Design and Imaging Protocol of a Prospective Multicenter Study in Korea.

PurposeInterest in unenhanced magnetic resonance imaging (MRI) screening for breast cancer is growing due to concerns about gadolinium deposition in the brain and the high cost of contrast-enhanced MRI. The purpose of this report is to describe the protocol of the Diffusion-Weighted Magnetic Resonance Imaging Screening Trial (DWIST), which is a prospective, multicenter, intraindividual comparative cohort study designed to compare the performance of mammography, ultrasonography, dynamic contrast-enhanced (DCE) MRI, and diffusion-weighted (DW) MRI screening in women at high risk of developing breast cancer.MethodsA total of 890 women with BRCA mutation or family history of breast cancer and lifetime risk ≥ 20% are enrolled. The participants undergo 2 annual breast screenings with digital mammography, ultrasonography, DCE MRI, and DW MRI at 3.0 T. Images are independently interpreted by trained radiologists. The reference standard is a combination of pathology and 12-month follow-up. Each image modality and their combination will be compared in terms of sensitivity, specificity, accuracy, positive predictive value, rate of invasive cancer detection, abnormal interpretation rate, and characteristics of detected cancers. The first participant was enrolled in April 2019. At the time of manuscript submission, 5 academic medical centers in South Korea are actively enrolling eligible women and a total of 235 women have undergone the first round of screening. Completion of enrollment is expected in 2022 and the results of the study are expected to be published in 2026.DiscussionDWIST is the first prospective multicenter study to compare the performance of DW MRI and conventional imaging modalities for breast cancer screening in high-risk women. DWIST is currently in the patient enrollment phase.Trial RegistrationClinicalTrials.gov Identifier: NCT03835897

Breast cancer screening for women at high risk: review of current guidelines from leading specialty societies.

The purpose of this article is to overview the existing breast cancer screening guidelines for women at high risk from world-leading specialty societies. Accumulation of evidence and development of accessible genetic testing strategies have changed the idea of breast cancer screening for high-risk women. Personalized tailor-made screening adjusted for risk factors has been conducted in accordance with guidelines. The use of imaging modalities other than mammography including contrast-enhanced MRI and other various strategies for improving screening are discussed. The present review also mentions the existing challenges in high-risk screening and the latest information based on two large-scale studies.

Current status of breast cancer screening in high-risk women in Japan.

Overseas, the importance for breast MRI screening for high-risk groups has been shown. However, the evidence among Japanese population was lacking. Therefore, we collaborated with the "Study on clinical and genetic characterization of hereditary breast and ovarian cancer and improvement in prognosis using genetic information in Japan" group, as part of the Comprehensive Research Project on the Promotion of Cancer Control, Health and Labour Sciences Research, and have been conducting the study entitled, "Study of the usefulness of MRI surveillance of BRCA1/2 mutation carriers" since 2014. In addition, we found that in the Japanese population also, the pathological and imaging characteristics differ between BRCA1 and BRCA2 mutation carriers, like in non-Japanese populations by the several reports. In high-risk females, risk categories such as BRCA1 or BRCA2 mutation carriers are very important. Furthermore, in the future, the optimal surveillance modalities and examination intervals would also vary according to the age, thinness of the breast (constitution), breast density (individual differences on mammography), etc.; this would be "personalized surveillance", and quality-assured MRI examination is of the essence. This review will present clinical trial data of prospective MRI surveillance in Japan, and summarize the current status of breast cancer screening in high-risk Japanese women.

Dynamic contrast-enhanced magnetic resonance imaging for risk-stratified screening in women with BRCA mutations or high familial risk for breast cancer: are we there yet?

Women at an elevated lifetime risk for breast cancer (BC), including carriers of pathogenic mutations in BC predisposition genes, are recommended intensified BC screening that includes annual mammography (MG) and annual breast MRI. Controversy exists regarding the clinical utility of MRI as a screening tool in high-risk women. This paper is intended to review recent advances and remaining areas of uncertainty in order to further facilitate the incorporation of breast MRI into an intensified BC screening protocol for women at high familial risk and BRCA carriers. A multidisciplinary team of medical oncologists and a radiologist specializing in the treatment of BC and high-risk patients searched PubMed to identify studies deemed to have the highest scientific value. Since none of the initial MRI studies were randomized, meta-analyses examining breast MRI screening in high-risk women were prioritized for inclusion. Breast MRI performs well in high-risk women, including mutation carriers. Breast MRI screening allows for the detection of early stage, likely curable invasive BC. It is mandatory that radiologists receive appropriate MRI training to reduce false positives and unnecessary biopsies. MRI screening is cost-effective in the highest risk patients and new clinical trials are open examining abbreviated and ultra-fast MRI techniques as a tool to drive down costs and improve specificity. As breast MRI is recommended as part of an intensified screening program in addition to mammography for high-risk women, it important that health care providers understand the benefits and limitations of this screening modality for high-risk women, as well as areas for further investigation.

Retrospective 15-Year Review of Anal Cytology Screening in Women at Mayo Clinic Rochester, Minnesota.

Anal cytology is a modality for anal cancer screening in high-risk women. In this retrospective study, we review risk factors associated with abnormal anal cytology and unsatisfactory anal cytology rates, and correlate findings of cytology with histological results. A retrospective cohort study of anal cytology screening in women at Mayo Clinic in Rochester, Minnesota from 2002 to 2018 was conducted. Three hundred fifty-seven women had a total of 592 anal cytologies performed. Three hundred seventeen women had screening anal cytology, whereas 40 women had anal cytology for surveillance given a history of anal intraepithelial neoplasia (AIN) or anal cancer. An unsatisfactory anal cytology result was found in 14.7%. Risk factors, type of follow-up, and correlation with histologic specimens were also reviewed. Histologic finding of AIN 2/3 correlated with abnormal anal cytology 84% of the time in this cohort. High-risk women should be screened on a periodic basis for anal cancer. Anal cytology is one possible modality that can be used. Further insight into AIN progression, regression, recurrence, and outcome after treatment will help direct future screening recommendations.

Mammography and ultrasonography for breast cancer screening in high-risk women

Mammography and ultrasonography for breast cancer screening in high-risk women

Performance Measures of Magnetic Resonance Imaging Plus Mammography in the High Risk Ontario Breast Screening Program.

The Ontario Breast Screening Program expanded in July 2011 to screen high-risk women age 30-69 years with annual magnetic resonance imaging (MRI) and digital mammography. This study examined the benefits of screening with mammography and MRI by age and risk criteria. This prospective cohort study included 8782 women age 30-69 years referred to the High Risk Ontario Breast Screening Program from July 2011 to June 2015, with final results to December 2016. Cancer detection rates, sensitivity, and specificity of MRI and mammography combined were compared with each modality individually within risk groups stratified by age using generalized estimating equation models. Prognostic features of screen-detected breast cancers were compared by modality using Fisher exact test. All P values are two-sided. Among 20 053 screening episodes, there were 280 screen-detected breast cancers (cancer detection rate = 14.0 per 1000, 95% confidence interval [CI] = 12.4 to 15.7). The sensitivity of mammography was statistically significantly lower than that of MRI plus mammography (40.8%, 95% CI = 29.3% to 53.5% vs 96.0%, 95% CI = 92.2% to 98.0%, P < .001). In mutation carriers age 30-39 years, sensitivity of the combination was comparable with MRI alone (100.0% vs 96.8%, 95% CI = 79.2% to 100.0%, P = .99) but with statistically significantly decreased specificity (78.0%, 95% CI = 74.7% to 80.9% vs 86.2%, 95% CI = 83.5% to 88.5%, P < .001). In women age 50-69 years, combining MRI and mammography statistically significantly increased sensitivity compared with MRI alone (96.3%, 95% CI = 90.6% to 98.6% vs 90.9%, 95% CI = 83.6% to 95.1%, P = .02), with a small but statistically significant decrease in specificity (84.2%, 95% CI = 83.1% to 85.2% vs 90.0%, 95% CI = 89.2% to 90.9%, P < .001). Screening high risk women age 30-39 years with annual MRI only may be sufficient for cancer detection and should be evaluated further, particularly for mutation carriers. Among women age 50-69 years, detection is most effective when mammography is included with annual MRI.

Evaluation of single-view contrast-enhanced mammography as novel reading strategy: a non-inferiority feasibility study

BackgroundGuidelines recommend screening of high-risk women using breast magnetic resonance imaging (MRI). Contrast-enhanced mammography (CEM) has matured, providing excellent diagnostic accuracy. To lower total radiation dose, evaluation of single-view (1 V) CEM exams might be considered instead of double-view (2 V) readings as an alternative reading strategy in women who cannot undergo MRI.MethodsThis retrospective non-inferiority feasibility study evaluates whether the use of 1 V results in an acceptable sensitivity for detecting breast cancer (non-inferiority margin, − 10%). CEM images from May 2013 to December 2017 were included. 1 V readings were performed by consensus opinion of three radiologists, followed by 2 V readings being performed after 6 weeks. Cases were considered “malignant” if the final BI-RADS score was ≥ 4, enabling calculation of sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Histopathological results or follow-up served as a gold standard.ResultsA total of 368 cases were evaluated. Mean follow-up for benign or negative cases was 20.9 months. Sensitivity decreased by 9.6% from 92.9 to 83.3% when only 1 V was used for evaluation (p < 0.001). The lower limit of the 90% confidence interval around the difference in sensitivity between 1 V and 2 V readings was − 15% and lies below the predefined non-inferiority margin of − 10%. Hence, non-inferiority of 1 V to 2 V reading cannot be concluded. AUC for 1 V was significantly lower, 0.861 versus 0.899 for 2 V (p = 0.0174).ConclusionNon-inferiority of 1 V evaluations as an alternative reading strategy to standard 2 V evaluations could not be concluded. 1 V evaluations had lower diagnostic performance compared with 2 V evaluations.Key Points• To lower radiation exposure used in contrast-enhanced mammography, we studied a hypothetical alternative strategy: single-view readings (1 V) versus (standard) double-view readings (2 V).• Based on our predefined margin of − 10%, non-inferiority of 1 V could not be concluded.• 1 V evaluation is not recommended as an alternative reading strategy to lower CEM-related radiation exposure.