ACR Appropriateness Criteria® Female Breast Cancer Screening: 2023 Update.

Early detection of breast cancer from regular screening substantially reduces breast cancer mortality and morbidity. Multiple different imaging modalities may be used to screen for breast cancer. Screening recommendations differ based on an individual's risk of developing breast cancer. Numerous factors contribute to breast cancer risk, which is frequently divided into three major categories: average, intermediate, and high risk. For patients assigned female at birth with native breast tissue, mammography and digital breast tomosynthesis are the recommended method for breast cancer screening in all risk categories. In addition to the recommendation of mammography and digital breast tomosynthesis in high-risk patients, screening with breast MRI is recommended. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Feasibility of Prospective Assignment of Initial Method of Detection of Breast Cancer: A Multicenter Pilot Study.

OBJECTIVE: To determine the feasibility of standardized, prospective assignment of initial method of detection (MOD) of breast cancer by radiologists in diverse practice settings. METHODS: This multicenter, retrospective study analyzed the rate of assignment of MOD in four geographically varied health systems. A universal protocol for basic MOD assignment was agreed upon by the authors before start of the pilot study. Radiologists at each site were instructed how to assign MOD. Charts were then reviewed to determine the frequency and accuracy of MOD assignment for all cases subsequently diagnosed with breast cancer. When available, data regarding frequency of tumor registry abstraction were also reviewed for frequency and accuracy. RESULTS: A total of 2,328 patients with a new diagnosis of breast cancer were evaluated across the sites over the study period. Of these patients, initial MOD was prospectively assigned by the radiologist in 94% of cases. Of the cases in which MOD was assigned, retrospective review confirmed accurate assignment in 96% of cases. CONCLUSIONS: Prospective, standardized assignment of initial MOD of breast cancer is feasible across different practice sites and can be accurately captured in tumor registries. Standard collection of MOD would provide critical data about the impact of screening mammography in the United States.

ACR Appropriateness Criteria® Breast Implant Evaluation: 2023 Update.

This document discusses the appropriate initial imaging in both asymptomatic and symptomatic patients with breast implants. For asymptomatic patients with saline implants, no imaging is recommended. If concern for rupture exists, ultrasound is usually appropriate though saline rupture is often clinically evident. The FDA recently recommended patients have an initial ultrasound or MRI examination 5 to 6 years after initial silicone implant surgery and then every 2 to 3 years thereafter. In a patient with unexplained axillary adenopathy with current or prior silicone breast implants, ultrasound and/or mammography are usually appropriate, depending on age. In a patient with concern for silicone implant rupture, ultrasound or MRI without contrast is usually appropriate. In the setting of a patient with breast implants and possible implant-associated anaplastic large cell lymphoma, ultrasound is usually appropriate as the initial imaging. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

ACR Appropriateness Criteria® Palpable Breast Masses: 2022 Update.

Palpable masses in women are the most common symptom associated with breast cancer. This document reviews and evaluates the current evidence for imaging recommendations of palpable masses in women less than 30 to over 40 years of age. There is also a review of several different scenarios and recommendations after initial imaging. Ultrasound is usually the appropriate initial imaging for women under 30 years of age. If ultrasound findings are suspicious or highly suggestive of malignancy (BIRADS 4 or 5), it is usually appropriate to continue with diagnostic tomosynthesis or mammography with image-guided biopsy. No further imaging is recommended if the ultrasound is benign or negative. The patient under 30 years of age with a probably benign ultrasound may undergo further imaging; however, the clinical scenario plays a role in the decision to biopsy. For women between 30 to 39 years of age, ultrasound, diagnostic mammography, tomosynthesis, and ultrasound are usually appropriate. Diagnostic mammography and tomosynthesis are the appropriate initial imaging for women 40 years of age or older, as ultrasound may be appropriate if the patient had a negative mammogram within 6 months of presentation or immediately after mammography findings are suspicious or highly suggestive of malignancy. If the diagnostic mammogram, tomosynthesis, and ultrasound findings are probably benign, no further imaging is necessary unless the clinical scenario indicates a biopsy. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

ACR Appropriateness Criteria® Imaging After Breast Surgery.

Given that 20% to 40% of women who have percutaneous breast biopsy subsequently undergo breast surgery, knowledge of imaging women with a history of benign (including high-risk) disease or breast cancer is important. For women who had surgery for nonmalignant pathology, the surveillance recommendations are determined by their overall risk. Higher-than-average risk women with a history of benign surgery may require screening mammography starting at an earlier age before 40 and may benefit from screening MRI. For women with breast cancer who have undergone initial excision and have positive margins, imaging with diagnostic mammography or MRI can sometimes guide additional surgical planning. Women who have completed breast conservation therapy for cancer should get annual mammography and may benefit from the addition of MRI or ultrasound to their surveillance regimen. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Age distributions of breast cancer diagnosis and mortality by race and ethnicity in US women.

BACKGROUND: Surveillance, Epidemiology, and End Results (SEER) data from 1973-2010 have been used to show that minority women have disproportionately higher percentages of breast cancers diagnosed at younger ages in comparison with White women. METHODS: The authors analyzed SEER 21 invasive breast cancer incidence data for 2014-2017 and National Center for Health Statistics mortality data for 2014-2018 and compared invasive incidence and mortality by age in non-Hispanic Black (NH-Black), Asian American/Pacific Islander (AAPI), Native American, and Hispanic women with those in non-Hispanic White (NH-White) women. They evaluated incidence rates and percentages of invasive breast cancer cases and breast cancer deaths occurring before the age of 50 years along with advanced-stage incidence rates and percentages in minority women versus NH-White women. RESULTS: Recent SEER data showed that invasive breast cancers were diagnosed at significantly younger ages in minority women versus NH-White women. Among women diagnosed with invasive breast cancer, compared with NH-White women, minority women were 72% more likely to be diagnosed under the age of 50 years (relative risk [RR], 1.72; 95% confidence interval [CI], 1.70-1.75), 58% more likely to be diagnosed with advanced-stage breast cancer under the age of 50 years (RR, 1.58; 95% CI, 1.55-1.61), and 24% more likely to be diagnosed with advanced-stage (regional or distant) breast cancer at all ages (RR, 1.24; 95% CI, 1.23-1.25). Among women dying of breast cancer, minority women were 127% more likely to die under the age of 50 years than NH-White women. CONCLUSIONS: NH-Black, AAPI, Native American, and Hispanic women have higher proportions of invasive breast cancers at younger ages and at advanced stages and breast cancer deaths at younger ages than NH-White women. LAY SUMMARY: This study analyzes the most recently available data on invasive breast cancers and breast cancer deaths in US women by age and race/ethnicity. Its findings show that non-Hispanic Black, Asian American/Pacific Islander, Native American, and Hispanic women have a higher percentage of invasive breast cancers at younger ages and at more advanced stages and a higher percentage of breast cancer deaths at younger ages than non-Hispanic White women.

Breast Cancer Screening Recommendations Inclusive of All Women at Average Risk: Update from the ACR and Society of Breast Imaging.

Breast cancer remains the most common nonskin cancer, the second leading cause of cancer deaths, and the leading cause of premature death in US women. Mammography screening has been proven effective in reducing breast cancer deaths in women age 40 years and older. A mortality reduction of 40% is possible with regular screening. Treatment advances cannot overcome the disadvantage of being diagnosed with an advanced-stage tumor. The ACR and Society of Breast Imaging recommend annual mammography screening beginning at age 40, which provides the greatest mortality reduction, diagnosis at earlier stage, better surgical options, and more effective chemotherapy. Annual screening results in more screening-detected tumors, tumors of smaller sizes, and fewer interval cancers than longer screening intervals. Screened women in their 40s are more likely to have early-stage disease, negative lymph nodes, and smaller tumors than unscreened women. Delaying screening until age 45 or 50 will result in an unnecessary loss of life to breast cancer and adversely affects minority women in particular. Screening should continue past age 74 years, without an upper age limit unless severe comorbidities limit life expectancy. Benefits of screening should be considered along with the possibilities of recall for additional imaging and benign biopsy and the less tangible risks of anxiety and overdiagnosis. Although recall and biopsy recommendations are higher with more frequent screening, so are life-years gained and breast cancer deaths averted. Women who wish to maximize benefit will choose annual screening starting at age 40 years and will not stop screening prematurely.

Mapping mammography in Arkansas: Locating areas with poor spatial access to breast cancer screening using optimization models and geographic information systems.

INTRODUCTION: Arkansans have some of the worst breast cancer mortality to incidence ratios in the United States (5th for Blacks, 4th for Whites, 7th overall). Screening mammography allows for early detection and significant reductions in mortality, yet not all women have access to these life-saving services. Utilization in Arkansas is well below the national average, and the number of FDA-approved screening facilities has decreased by 38% since 2001. Spatial accessibility plays an important role in whether women receive screenings. METHODS: We use constrained optimization models within a geographic information system (GIS) to probabilistically allocate women to nearby screening facilities, accounting for facility capacity and patient travel time. We examine accessibility results by rurality derived from rural-urban commuting area (RUCA) codes. RESULTS: Under most models, screening capacity is insufficient to meet theoretical demand given travel constraints. Approximately 80% of Arkansan women live within 30 minutes of a screening facility, most of which are located in urban and suburban areas. The majority of unallocated demand was in Small towns and Rural areas. CONCLUSIONS: Geographic disparities in screening mammography accessibility exist across Arkansas, but women living in Rural areas have particularly poor spatial access. Mobile mammography clinics can remove patient travel time constraints to help meet rural demand. More broadly, optimization models and GIS can be applied to many studies of healthcare accessibility in rural populations.

Relationships Between Health Care Disparities and Coverage Policies for Breast, Colon, and Lung Cancer Screening.

Disparities in outcomes exist for breast, colon, and lung cancer among diverse populations, particularly racial and ethnic underrepresented minorities (URMs) and individuals from lower socioeconomic status. For example, blacks experience mortality rates up to about 42% higher than whites for these cancers. Furthermore, although overall death rates have been declining, the differential access to screening and care has aggravated disparities. Our purpose is to assess how the coverage policies of CMS and the United States Preventive Services Task Force (USPSTF) influence these disparities. Additionally, barriers are often encountered in accessing screening tests and receiving prompt treatment. To narrow, and potentially eliminate, outcomes disparities, CMS and USPSTF could consider revising their decision-making processes regarding coverage. Some options include (1) extending their evidence base to include observational studies that involve groups at higher risk; (2) lowering the threshold ages for screening to encompass differences in incidence; (3) CMS approving screening CT colonography coverage, which can even increase compliance with other screening tests; (4) clarifying and streamlining guidelines; (5) supporting research on improving access to screening; and (6) encouraging the development of more navigation services for URMs.

Change in Mammography Use Following the Revised Guidelines from the U.S. Preventive Services Task Force.

The U.S. Preventive Services Task Force (USPSTF) recommended screening mammography every 1-2 years for women 40 years and older in 2002, and changed its recommendations in 2009 to no routine screening for women between 40 and 49 years of age; and biennial screening for women between 50 and 74 years of age. This study evaluates the change in mammographic use after the issuance of the revised recommendations. Women who participated in a cross-sectional study of breast cancer risk factors from 2007 to 2013 were asked if they had received a mammogram in the preceding 2 years. All 3442 study participants who enrolled in the study after January 1, 2011 were matched by race, age, and educational level with women enrolled between 2007 and 2010. The proportions of women who stated they had received a mammogram in the past 2 years were compared between the two groups. One fourth of the participants were African American and 39% were 40-49 years of age. Among white women, significant decreases in recent mammogram use from 2007-2010 to 2011-2013 were detected for women 40-49 years of age (-10.3%, p < 0.001) and 50-74 years of age (-8.8%, p < 0.001). Among African-American women, the change in recent mammogram use was not statistically significant for women 40-49 years of age (-2.7%, p = 0.440) or 50-74 years of age (-2.2%, p = 0.398). Following the change in the USPSTF guidelines, mammography use among white women declined; however, no change was observed among African-American women.

Autophagy in the brain of neonates following hypoxia-ischemia shows sex- and region-specific effects.

Autophagy is responsible for the bulk degradation of cytoplasmic contents including organelles through the lysosomal machinery. Neonatal hypoxia-ischemia (HI) causes cell death in the brain by caspase-dependent and independent pathways. Ischemic insults also increase the formation of autophagosomes and activate autophagy. This study assessed the possible sex- and region-specific differences of autophagy activity in neonates subjected to HI brain injury. HI males had a modest decrease in lysosome numbers with no effect on LC3B-II protein in the cortex. In contrast, HI females had decreased lysosome numbers and their LC3B-II protein expression was significantly increased in the cortex following HI. In the hippocampus, both HI males and all females had increased numbers of autolysosomes suggesting activation of autophagy but with no effect on lysosome numbers, or Beclin-1 or LC3B protein levels. Males and females had increases in caspase 3/7 activity in their cortices and hippocampi following HI, though the increases were three to sixfold greater in females. The present data: (a) confirm greater caspase activation in the brains of females compared to males following HI; (b) suggest a partial failure to degrade LC3B-II protein in cortical but not hippocampal lysosomes of females as compared to males following neonatal HI; (c) all females have greater basal autophagy activity than males which may protect cells against injury by increasing cell turnover and (d) demonstrate that autophagy pathways are disturbed in regional- and sex-specific patterns in the rat brain following neonatal HI.

Gene expression in blood is associated with risperidone response in children with autism spectrum disorders.

Children with autism spectrum disorders (ASDs) often have severe behavioral problems. Not all children with these problems respond to atypical antipsychotic medications; therefore, we investigated whether peripheral blood gene expression before treatment with risperidone, an atypical antipsychotic, was associated with improvements in severe behavioral disturbances 8 weeks following risperidone treatment in 42 ASD subjects (age 112.7±51.2 months). Exon expression levels in blood before risperidone treatment were compared with pre-post risperidone change in Aberrant Behavior Checklist-Irritability (ABC-I) scores. Expression of exons within five genes was correlated with change in ABC-I scores across all risperidone-treated subjects: GBP6, RABL5, RNF213, NFKBID and RNF40 (α<0.001). RNF40 is located at 16p11.2, a region implicated in autism and schizophrenia. Thus, these genes expressed before treatment were associated with subsequent clinical response. Future studies will be needed to confirm these results and determine whether this expression profile is associated with risperidone response in other disorders, or alternative antipsychotic response within ASD.

Transient ischemic attacks characterized by RNA profiles in blood.

OBJECTIVE: Transient ischemic attacks (TIA) are common. Though systemic inflammation and thrombosis are associated with TIA, further study may provide insight into TIA pathophysiology and possibly lead to the development of treatments specifically targeted to TIA. We sought to determine whether gene expression profiles in blood could better characterize the proinflammatory and procoagulant states in TIA patients. METHODS: RNA expression in blood of TIA patients (n = 26) was compared to vascular risk factor control subjects without symptomatic cardiovascular disease (n = 26) using Affymetrix U133 Plus 2.0 microarrays. Differentially expressed genes in TIA were identified by analysis of covariance and evaluated with cross-validation and functional analyses. RESULTS: Patients with TIA had different patterns of gene expression compared to controls. There were 480 probe sets, corresponding to 449 genes, differentially expressed between TIA and controls (false discovery rate correction for multiple comparisons, p ≤ 0.05, absolute fold change ≥1.2). These genes were associated with systemic inflammation, platelet activation, and prothrombin activation. Hierarchical cluster analysis of the identified genes suggested the presence of 2 patterns of RNA expression in patients with TIA. Prediction analysis identified a set of 34 genes that discriminated TIA from controls with 100% sensitivity and 100% specificity. CONCLUSION: Patients with recent TIA have differences of gene expression in blood compared to controls. The 2 gene expression profiles associated with TIA suggests heterogeneous responses between subjects with TIA that may provide insight into cause, risk of stroke, and other TIA pathophysiology.

Screening breast MR imaging in women with a history of lobular carcinoma in situ.

PURPOSE: To assess the utility of screening magnetic resonance (MR) imaging in the detection of otherwise occult breast cancers in women with a history of lobular carcinoma in situ (LCIS). MATERIALS AND METHODS: This HIPAA-compliant study received institutional review board approval. The need for informed consent was waived. Retrospective review of the database yielded 670 screening breast MR studies obtained between January 2003 and September 2008 in 220 women with a history of LCIS. MR and mammographic findings were reviewed. Number of cancers diagnosed, method of detection, and tumor characteristics were examined. The cumulative incidence of developing breast cancer as detected with MR imaging and mammography was calculated. Breast density was examined as a prognostic factor in the cumulative incidence analysis. RESULTS: Biopsy was recommended in 63 lesions seen in 58 (9%) of 670 screening MR studies. Eight additional lesions were identified at short-term follow-up MR imaging for a total of 71 lesions in 59 patients. Twelve cancers (20%) were identified in 60 lesions sampled. Biopsy was recommended in 26 additional lesions identified at mammography; biopsy was performed in 25 of these lesions and revealed malignancy in five (20%). Overall, 17 cancers were detected in 14 patients during the study period. Of these, 12 were detected with MR imaging alone, and five were detected with mammography alone. Of the 12 cancers detected at MR imaging, there were nine invasive cancers and three cases of ductal carcinoma in situ (DCIS). Of the five cancers detected at mammography, two were invasive and three were DCIS. CONCLUSION: MR imaging is a useful adjunct modality with which to screen women with a history of LCIS at high-risk of developing breast cancer, resulting in a 4.5% incremental cancer detection rate. Sensitivity in the detection of breast cancers with a combination of MR imaging and mammography was higher than sensitivity of either modality alone.

Extragenitourinary malakoplakia in a patient with myeloma clinically mimicking extramedullary myelomatous disease.

Malakoplakia is a rare granulomatous disorder of unknown etiology and usually affects patients with underlying immunosuppression. This disorder usually involves the genitourinary tract but has been reported in a wide array of anatomical sites. We present a case of extragenitourinary malakoplakia, developing in a patient with a history of plasma cell myeloma, which clinically mimicked recurrent extramedullary myelomatous involvement. Radiologically, this lesion was a 10-cm soft-tissue mass located in the left flank and iliacus muscle. Excisional biopsy revealed a histiocytic infiltrate with histologic features diagnostic of malakoplakia. This case demonstrates the clinical and pathologic diagnostic challenges of malakoplakia arising outside the genitourinary tract. Given that it can closely mimic malignancy in such settings, malakoplakia should be considered in the differential diagnosis of soft-tissue masses developing in patients with hematologic malignancy and iatrogenic immunosuppression. This case highlights the importance for awareness on the part of clinicians, radiologists, and pathologists that malakoplakia can present as a soft-tissue mass.

Corticosteroid effects on blood gene expression in Duchenne muscular dystrophy.

Though Deflazacort and prednisone improve clinical endpoints in Duchenne muscular dystrophy (DMD) patients, Deflazacort produces fewer side effects. As mechanisms of improvement and side effect differences remain unknown, we evaluated effects of corticosteroid administration on gene expression in blood of DMD patients. Whole blood was obtained from 14 children and adolescents with DMD treated with corticosteroids (DMD-STEROID) and 20 DMD children and adolescents naïve to corticosteroids (DMD). The DMD-STEROID group was further subdivided into Deflazacort and prednisone groups. Affymetrix U133 Plus 2.0 expression microarrays were used to evaluate mRNA expression. Expression of 524 probes changed with corticosteroids, including genes in iron trafficking and the chondroitin sulfate biosynthesis pathway. Deflazacort compared with prednisone yielded 508 regulated probes, including many involved in adipose metabolism. These genes and pathways help explain mechanisms of efficacy and side effects of corticosteroids, and could provide new treatment targets for DMD and other neuromuscular disorders.

Intracerebral hemorrhage injury mechanisms: glutamate neurotoxicity, thrombin, and Src.

The mechanisms accounting for variable increases in blood flow and seizures following intracerebral hemorrhage (ICH) are unknown. Local cerebral glucose utilization (LCGU) studies performed to address this issue demonstrate increased LCGU within hours around an ICH that is blocked by NMDA and AMPA glutamate receptor antagonists. Local injections of NMDA or AMPA increased LCGU whereas glutamate did not, suggesting an ICH effect on glutamate uptake or glutamate receptors. To address these possibilities, we performed genomic studies of brain following ICH. Among the many regulated genes, an Src family member, Lyn, increased expression over 20-fold. This was important, since Src is known to phosphorylate NMDA receptors and augment their function, and thrombin is known to activate PARs that activate Src. This prompted us to study the Src antagonist, PP2. PP2 decreased LCGU and cell death around ICH and improved behavioral function following ICH. This data leads us to suggest our hypothesis, that ICH, possibly via thrombin activation of protease-activated receptors, activates Src that phosphorylates NMDA receptors and other proteins that mediate injury after ICH.

Left Atrial Drainage of a Persistent Left Superior Vena Cava.

Although the most common form of the persistent left superior vena cava anomaly is usually clinically silent and often discovered incidentally, the risk of developing cyanosis, heart failure, and embolic cerebrovascular events is high among cases where the anomaly causes a right to left shunt. A rare case of persistent left superior vena cava draining into the left atrium through the superior left pulmonary vein is presented with a discussion of the embryology, morphologic forms, and clinical significance of the persistent left superior vena cava.

A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins.

Modern methods that use systematic, quantitative and unbiased approaches are making it possible to discover proteins altered by a disease. To identify proteins that might be differentially expressed in autism, serum proteins from blood were subjected to trypsin digestion followed by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) on time-of-flight (TOF) instruments to identify differentially expressed peptides. Children with autism 4-6 years of age (n=69) were compared to typically developing children (n=35) with similar age and gender distributions. A total of 6348 peptide components were quantified. Of these, five peptide components corresponding to four known proteins had an effect size >0.99 with a P<0.05 and a Mascot identification score of 30 or greater for autism compared to controls. The four proteins were: Apolipoprotein (apo) B-100, Complement Factor H Related Protein (FHR1), Complement C1q and Fibronectin 1 (FN1). In addition, apo B-100 and apo A-IV were higher in children with high compared to low functioning autism. Apos are involved in the transport of lipids, cholesterol and vitamin E. The complement system is involved in the lysis and removal of infectious organisms in blood, and may be involved in cellular apoptosis in brain. Despite limitations of the study, including the low fold changes and variable detection rates for the peptide components, the data support possible differences of circulating proteins in autism, and should help stimulate the continued search for causes and treatments of autism by examining peripheral blood.