Enhancing Early-Stage Breast Cancer Survivorship: Evidence-Based Strategies, Surveillance Testing, and Imaging Guidelines.

Addressing the challenges of survivorship necessitates a comprehensive, patient-centered approach, focusing on mitigating risk through lifestyle modification, identifying distant recurrence, and optimization of breast imaging. This article will discuss the current and emerging clinical strategies for the survivorship period, advocating a multidisciplinary and comprehensive approach. In this manner, early-stage breast cancer survivors are empowered to navigate their journey with enhanced knowledge, facilitating a transition to life beyond cancer.

Comparative Performance of Contrast-enhanced Mammography, Abbreviated Breast MRI, and Standard Breast MRI for Breast Cancer Screening.

Background Contrast-enhanced mammography (CEM) and abbreviated breast MRI (ABMRI) are emerging alternatives to standard MRI for supplemental breast cancer screening. Purpose To compare the diagnostic performance of CEM, ABMRI, and standard MRI. Materials and Methods This single-institution, prospective, blinded reader study included female participants referred for breast MRI from January 2018 to June 2021. CEM was performed within 14 days of standard MRI; ABMRI was produced from standard MRI images. Two readers independently interpreted each CEM and ABMRI after a washout period. Examination-level performance metrics calculated were recall rate, cancer detection, and false-positive biopsy recommendation rates per 1000 examinations and sensitivity, specificity, and positive predictive value of biopsy recommendation. Bootstrap and permutation tests were used to calculate 95% CIs and compare modalities. Results Evaluated were 492 paired CEM and ABMRI interpretations from 246 participants (median age, 51 years; IQR, 43-61 years). On 49 MRI scans with lesions recommended for biopsy, nine lesions showed malignant pathology. No differences in ABMRI and standard MRI performance were identified. Compared with standard MRI, CEM demonstrated significantly lower recall rate (14.0% vs 22.8%; difference, -8.7%; 95% CI: -14.0, -3.5), lower false-positive biopsy recommendation rate per 1000 examinations (65.0 vs 162.6; difference, -97.6; 95% CI: -146.3, -50.8), and higher specificity (87.8% vs 80.2%; difference, 7.6%; 95% CI: 2.3, 13.1). Compared with standard MRI, CEM had significantly lower cancer detection rate (22.4 vs 36.6; difference, -14.2; 95% CI: -28.5, -2.0) and sensitivity (61.1% vs 100%; difference, -38.9%; 95% CI: -66.7, -12.5). The performance differences between CEM and ABMRI were similar to those observed between CEM and standard MRI. Conclusion ABMRI had comparable performance to standard MRI and may support more efficient MRI screening. CEM had lower recall and higher specificity compared with standard MRI or ABMRI, offset by lower cancer detection rate and sensitivity compared with standard MRI. These trade-offs warrant further consideration of patient population characteristics before widespread screening with CEM. Clinical trial registration no. NCT03517813 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Chang in this issue.

Preoperative Breast MRI: Current Evidence and Patient Selection.

Breast MRI is the most sensitive imaging modality for the assessment of newly diagnosed breast cancer extent and can detect additional mammographically and clinically occult breast cancers in the ipsilateral and contralateral breasts. Nonetheless, appropriate use of breast MRI in the setting of newly diagnosed breast cancer remains debated. Though highly sensitive, MRI is less specific and may result in false positives and overestimation of disease when MRI findings are not biopsied prior to surgical excision. Furthermore, improved anatomic depiction of breast cancer on MRI has not consistently translated to improved clinical outcomes, such as lower rates of re-excision or breast cancer recurrence, though there is a paucity of well-designed studies examining these issues. In addition, current treatment paradigms have been developed in the absence of this more accurate depiction of disease span, which likely has limited the value of MRI. These issues have led to inconsistent and variable utilization of preoperative MRI across practice settings and providers. In this review, we discuss the history of breast MRI and its current use and recommendations with a focus on the preoperative setting. We review the evidence surrounding the use of preoperative MRI in the evaluation of breast malignancies and discuss the data on breast MRI in the setting of specific patient factors often used to determine breast MRI eligibility, such as age, index tumor phenotype, and breast density. Finally, we review the impact of breast MRI on surgical outcomes (re-excision and mastectomy rates) and long-term breast recurrence and survival outcomes.

Mucosal Immune Profiles Associated with Diarrheal Disease Severity in Shigella- and Enteropathogenic Escherichia coli-Infected Children Enrolled in the Global Enteric Multicenter Study.

Enteropathogenic Escherichia coli (EPEC) and Shigella are etiologic agents of diarrhea in children <5 years old living in resource-poor countries. Repeated bouts of infection lead to lifelong morbidity and even death. The goal of this study was to characterize local mucosal immune responses in Shigella- and EPEC-infected children <5 years of age with moderate to severe diarrhea (MSD) enrolled in the Global Enteric Multicenter Study (GEMS). We hypothesized that infection with each of these pathogens would induce distinct gut mucosal immune profiles indicative of disease etiology and severity. To test this hypothesis, innate and adaptive immune markers were measured in stools from children with diarrhea due to EPEC, Shigella, or other organisms and in children who had no diarrhea. Shigella-positive diarrhea evoked robust proinflammatory and TH1/TH2 cytokine responses compared to diarrhea caused by EPEC or other organisms, with the exception of interleukin 5 (IL-5), which was associated with EPEC infection. The presence of IL-1ß, IL-4, IL-16, and tumor necrosis factor beta (TNF-ß) was associated with the absence of dysentery. EPEC-positive diarrhea evoked high levels of IL-1ß, vascular endothelial growth factor (VEGF), and IL-10. Granulocyte-macrophage colony-stimulating factor (GM-CSF) had opposing roles in disease severity, being associated with absence of diarrhea in EPEC-infected children and with dysenteric Shigella infection. High levels of antigen-specific antibodies were detected in the controls and children with Shigella without dysentery, which suggests a protective role against severe disease. In summary, this study identified distinct local immune responses associated with two clinically relevant diarrheagenic pathogens, Shigella and EPEC, in children and identified protective immune phenotypes that can inform the development of preventive measures. IMPORTANCE Shigella and enteropathogenic Escherichia coli are primary agents of moderate to severe diarrhea in children <5 years of age living in resource-poor countries. Repeated bouts of illness lead to lifelong health impairment and even death. Aiming to understand the local host immunity to these pathogens in relation to disease prognosis and to identify prophylaxis and therapeutic targets, we investigated innate and adaptive immune profiles in stools from children infected with EPEC with and without diarrhea, Shigella with and without dysentery, and controls in well characterized clinical samples obtained during the Global Enteric Multicenter Study. For the first time, we report pathogen-specific mucosal immune profiles associated with severity or absence of disease in children <5 years of age that can inform prevention and treatment efforts.

Women and thyroid cancer incidence: overdiagnosis versus biological risk.

PURPOSE OF THE REVIEW: Our aim is to discuss the concepts of sex and gender in the context of thyroid cancer epidemiology. RECENT FINDINGS: It has been long-established in global epidemiologic data that thyroid cancer incidence rates are higher in women than men. However, what has been less well understood is whether this reflects sex disparities in cancer susceptibility, gender disparities in detection, or a combination. A recent meta-analysis of autopsy data from individuals who were not known to have thyroid cancer in their lifetime demonstrated no difference in the prevalence of thyroid cancer in women and men, suggesting that gender differences may be the reason for gender-based differences in thyroid cancer detection. This finding, and sex differences in auto immunity and other factors that may affect cancer susceptibility are explored. SUMMARY: Additional research to explore gender- and sex-specific data on thyroid cancer would inform our understanding of the differences and similarities between men and women in susceptibility and detection of thyroid cancer and help to optimize disease management for all genders and both sexes.

A gene-diet interaction controlling relative intake of dietary carbohydrates and fats.

OBJECTIVE: Preference for dietary fat vs. carbohydrate varies markedly across free-living individuals. It is recognized that food choice is under genetic and physiological regulation, and that the central melanocortin system is involved. However, how genetic and dietary factors interact to regulate relative macronutrient intake is not well understood. METHODS: We investigated how the choice for food rich in carbohydrate vs. fat is influenced by dietary cholesterol availability and agouti-related protein (AGRP), the orexigenic component of the central melanocortin system. We assessed how macronutrient intake and different metabolic parameters correlate with plasma AGRP in a cohort of obese humans. We also examined how both dietary cholesterol levels and inhibiting de novo cholesterol synthesis affect carbohydrate and fat intake in mice, and how dietary cholesterol deficiency during the postnatal period impacts macronutrient intake patterns in adulthood. RESULTS: In obese human subjects, plasma levels of AGRP correlated inversely with consumption of carbohydrates over fats. Moreover, AgRP-deficient mice preferred to consume more calories from carbohydrates than fats, more so when each diet lacked cholesterol. Intriguingly, inhibiting cholesterol biosynthesis (simvastatin) promoted carbohydrate intake at the expense of fat without altering total caloric consumption, an effect that was remarkably absent in AgRP-deficient mice. Finally, feeding lactating C57BL/6 dams and pups a cholesterol-free diet prior to weaning led the offspring to prefer fats over carbohydrates as adults, indicating that altered cholesterol metabolism early in life programs adaptive changes to macronutrient intake. CONCLUSIONS: Together, our study illustrates a specific gene-diet interaction in modulating food choice.

It's a Two-Way Street: Giving and Receiving Feedback to the Unaware.

Giving and receiving constructive feedback is a valuable skill and an evolving process due to improved understanding and changes in culture. This article provides a practical review of key elements of effective feedback skills and strategies for providing constructive feedback, with a focus on how to address recipients who may have impaired insight into the issue at hand. Commonly known tips and tricks include direct, immediate, and specific feedback delivered in a safe setting and in a conversational manner. This article specifically considers how the feedback will be heard or accepted by the intended recipient, in order for the educator to best overcome hurdles in relaying constructive criticism.

When cardiomyopathy, cancer, and COVID-19 collide: A case report.

Malignancy has historically prohibited solid organ transplant; however, patients with effectively treated, favorable-risk cancers should not necessarily be eliminated as transplant candidates. These cases require careful review by a multidisciplinary team. Here, we report the case of a woman with end-stage heart failure undergoing heart transplant evaluation during the COVID pandemic who was found to have early-stage, hormone receptor-positive breast cancer. Given her favorable cancer-related prognosis, a multidisciplinary committee recommended lumpectomy, accelerated partial breast irradiation, and adjuvant aromatase inhibitor therapy for definitive treatment to allow for consideration of orthotopic heart transplant.

Breast Magnetic Resonance Imaging Audit: Pitfalls, Challenges, and Future Considerations.

Breast magnetic resonance (MR) imaging is the most sensitive imaging modality for breast cancer detection and guidelines recommend its use, in addition to screening mammography, for high-risk women. The most recent American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) manual coordinated cross-modality BI-RADS terminology and established an outcome monitoring section that helps guide a medical imaging outcomes audit. This article provides a framework for performing a breast MR imaging audit in clinical practice, incorporating ACR BI-RADS guidance and more recently published data, clarifies common pitfalls, and discusses audit challenges related to evolving clinical practice.

Effect of Doxycycline on Aneurysm Growth Among Patients With Small Infrarenal Abdominal Aortic Aneurysms: A Randomized Clinical Trial.

Importance: Abdominal aortic aneurysms affect more than 3% of US older adults. Objective: To test whether doxycycline reduces the growth of abdominal aortic aneurysm over 2 years as measured by maximum transverse diameter. Design, Setting, and Participants: Parallel, 2-group, randomized clinical trial that was conducted at 22 US clinical centers between May 2013 and January 2017, and enrolled patients 50 years or older with small (3.5-5.0 cm for men, 3.5-4.5 cm for women) infrarenal aneurysms. The final date of follow-up was July 31, 2018. Interventions: Patients were randomized to receive twice daily for 2 years doxycycline 100 mg orally (as capsules) (n = 133) or placebo (n = 128). Main Outcomes and Measures: The primary outcome was change in abdominal aortic aneurysm maximum transverse diameter measured from CT images at baseline and follow-up at 2 years. Patients were assigned ranks based on the maximum transverse diameter (measured or imputed) of the aorta and also if they underwent aneurysm repair or died. The ranks were converted to scores having a normal distribution to facilitate the primary analysis ("normal scores"). Results: Of 261 patients randomized, no follow-up CT scans were obtained on 7 (3%), leaving a final analysis set of 129 patients assigned to doxycycline and 125 to placebo (mean [SD] age, 71.0 years [7.4 years], 35 women [14%]). The outcome normal scores used in the primary analysis were based on maximum transverse diameter (measured or imputed) in 113 patients (88%) in the doxycycline group and 112 patients (90%) in the placebo group; aneurysm repair in 13 (10%) and 9 (7%), and death in 3 (2%) and 4 (3%), respectively. The primary outcome, normal scores reflecting change in aortic diameter, did not differ significantly between the 2 groups, mean change in normal scores, 0.0262 vs -0.0258 (1-sided P = .71). Mean (SD) baseline maximum transverse diameter was 4.3 cm (0.4 cm) for doxycycline and 4.3 cm (0.4 cm) for placebo. At the 2-year follow-up, the change in measured maximum transverse diameter was 0.36 cm (95% CI, 0.31 to 0.40 cm) for 96 patients in the doxycycline group vs 0.36 cm (95% CI, 0.30 to 0.41 cm) for 101 patients in the placebo group (difference, 0.0; 95% CI, -0.07 to 0.07 cm; 2-sided P = .93). No patients were withdrawn from the study because of adverse effects. Joint pain occurred in 84 of 129 patients (65%) with doxycycline and 79 of 125 (63%) with placebo. Conclusions and Relevance: Among patients with small infrarenal abdominal aortic aneurysms, doxycycline compared with placebo did not significantly reduce aneurysm growth at 2 years. These findings do not support the use of doxycycline for reducing the growth of small abdominal aortic aneurysms. Trial Registration: ClinicalTrials.gov Identifier: NCT01756833.

A phased approach to implementing the Breast Imaging Reporting and Data System (BI-RADS) in low-income and middle-income countries.

BACKGROUND: Successful breast cancer detection programs rely on standardized reporting and interpreting systems, such as the Breast Imaging Reporting and Data System (BI-RADS), to improve system performance. In low-income and middle-income countries, evolving diagnostic programs have insufficient resources to either fully implement BI-RADS or to periodically evaluate the program's performance, which is a necessary component of BI-RADS. This leads to inconsistent breast ultrasound interpretation and a failure to improve performance. METHODS: The authors applied the Breast Health Global Initiative's phased implementation strategy to implement diagnostic ultrasound and BI-RADS within the context of a limited-resource setting. RESULTS: The authors recommended starting with triage ultrasound to distinguish suspicious masses from normal breast tissue and benign masses such as cysts because the majority of health workers performing ultrasounds at this level have minimal breast imaging experience. Transitioning to full diagnostic ultrasound with condensed or full BI-RADS should occur after performance and quality metrics have been met. CONCLUSIONS: Transitioning through these phases across facilities likely will occur at different times, particularly in rural versus urban settings.

The Impact of Preoperative Breast MRI on Surgical Management of Women with Newly Diagnosed Ductal Carcinoma In Situ.

RATIONALE AND OBJECTIVES: Use of preoperative breast MRI (pMRI) to evaluate ductal carcinoma in situ (DCIS) extent is controversial due to limited data on its impact on surgical management. We sought to evaluate the effect of pMRI on surgical management of women with core needle biopsy (CNB)-diagnosed pure DCIS at a multidisciplinary academic institution. MATERIALS AND METHODS: This retrospective study included all women with CNB-diagnosed DCIS (1/2004-12/2013) without prior ipsilateral breast cancer and who underwent surgery within 180 days of diagnosis. Patient features, number of CNBs and surgeries, and single successful breast conserving surgery (BCS) rate were compared between pMRI and no-pMRI cohorts. Number of surgeries and single BCS success rates were also compared to published US (SEER) and Danish National Registry data. RESULTS: Among the 373 women included, no clinical differences were identified between the pMRI (n = 332) and no-pMRI (n = 41) cohorts (p > 0.05). The pMRI group experienced a higher additional CNB rate (30% vs. 7%, p = 0.002) but fewer total surgeries (mean = 1.2 vs. 1.5, p < 0.001) than the no-pMRI group. Among the 245 women for whom BCS was attempted, the pMRI cohort underwent fewer mean surgeries (1.3 vs. 1.7, p < 0.001) with a greater single successful BCS rate (77% vs. 43%, p < 0.001). Compared to published data, women with pMRI who underwent BCS experienced fewer surgeries (difference (Δ) = -0.22 vs. -0.17, p < 0.001) with a higher single successful BCS rate (Δ = +20% vs. +14%, p < 0.001). CONCLUSION: pMRI may improve surgical management of DCIS at multidisciplinary centers with breast cancer specialists.

Asymptomatic carotid stenosis is associated with mobility and cognitive dysfunction and heightens falls in older adults.

BACKGROUND: Atherosclerosis of the carotid bifurcation with plaque formation causes asymptomatic carotid artery stenosis (ACAS), which may also be associated with cerebral hypoperfusion. Cerebral hypoperfusion adversely affects multiple aspects of mobility and cognition. This study tests the hypothesis that community-dwelling older adults with a 50% or greater diameter-reducing ACAS will have mobility and cognitive impairments that heighten their risk for falls. METHODS: Eighty community-dwelling adults completed a mobility assessment (Short Physical Performance Battery, Berg Balance Scale, Four Square Step Test, Dynamic Gait Index, Timed Up and Go, and gait speed), self-reported physical function (Activities-Specific Balance Confidence, SF-12 Physical Function Component), and cognitive tests (Mini-Mental State Examination). Falls were recorded for the past 6 months. Standardized carotid ultrasound examination classified participants into no stenosis (<50% diameter reduction) (n = 54), moderate stenosis (50%-69%) (n = 17), and high-grade stenosis (70%-99%) (n = 9) groups. Linear and logistic regression analyses determined the associations between these measures and the degree of stenosis (three groups). RESULTS: Logistic regression analysis showed their degree of stenosis was associated with reductions in mobility (Short Physical Performance Battery [P = .008], Berg Balance Scale [P = .0008], Four Square Step Test [P = .005], DGI [P = .0001], TUG [P = .0004], gait speed [P = .02]), perceived physical function (ABC [P < .0001], SF-12 Physical Function Component [P < .0001]), and cognition (MMSE [P = .003]). Adults with moderate- and high-grade stenosis had a greater incidence of falls compared with those without stenosis (relative risk, 2.86; P = .01). Results remained unchanged after adjustment for age, sex and cardiovascular risk factors. CONCLUSIONS: ACAS is associated with impaired mobility and cognition that are accompanied with increased fall risk. These impairments increased with worsening severity.

The Radiologist's Role in a Breast Multidisciplinary Tumor Board.

Breast multidisciplinary tumor boards (MTBs) play an important role in determining treatment. This article serves as a guide for the radiologist participating in a breast MTB, as the information presented at MTB can significantly influence treatment plans and dictate future steps for further patient work-up. Multidisciplinary tumor board preparation involves a careful review of the patient's history while gathering all relevant imaging studies, and reinterpreting them when appropriate. Presented images should be carefully selected, annotated, and displayed clearly before providing final recommendations for localization and incompletely assessed findings. Anatomic staging factors from the AJCC Breast Cancer Staging System, such as tumor size and degree of suspected skin involvement, should be described. In addition, there are many other types of information that the treatment specialists want to know. The surgeon is interested in anatomic information that will help them decide whether breast conservation therapy is feasible or if local structures, such as the nipple, can be spared. The radiation oncologist may need to know whether accelerated partial breast irradiation is feasible or if postmastectomy radiation therapy is indicated. The medical oncologist is looking for factors that may provide an indication for neoadjuvant therapy and ensuring there is a reliable follow-up method for evaluating the response to treatment, such as comparative MRI. Additionally, all specialists need to know the extent of suspected nodal involvement. By clearly and comprehensively presenting this information to the rest of the MTB team, the radiologist provides a vital contribution that guides treatment and ensures adherence to clinical guidelines.

A Review of Innovative Teaching Methods.

Teaching is one of the important roles of an academic radiologist. Therefore, it is important that radiologists are taught how to effectively educate and, in turn, to act as role models of these skills to trainees. This is reinforced by the Liaison Committee on Medical Education which has the requirement that all residents who interact with and teach medical students must undergo training in effective methods of teaching. Radiologists are likely familiar with the traditional didactic lecture-type teaching format. However, there are many newer innovative teaching methods that could be added to the radiologist's teaching repertoire, which could be used to enhance the traditional lecture format. The Association of University Radiologists Radiology Research Alliance Task Force on Noninterpretive Skills therefore presents a review of several innovative teaching methods, which include the use of audience response technology, long-distance teaching, the flipped classroom, and active learning.

Practical Presentation Pearls: Evidence-based Recommendations From the Psychology and Physiology Literature.

Oral presentations remain a common teaching method in academic radiology. The goal of these presentations is to transfer knowledge from the presenter's brain to brains in the audience in a way that sticks. A number of studies from the recent psychological and physiological literature offer some rather practical and evidence-based advice on ways to optimize our oral presentations. The purpose of this paper is to summarize this work, and to give examples of how it can be harnessed to increase the efficacy of radiology presentations, whether they are for resident education, a continuing medical education course, or for a scientific presentation at a national radiology meeting.

Assessment of Quantitative Magnetic Resonance Imaging Background Parenchymal Enhancement Parameters to Improve Determination of Individual Breast Cancer Risk.

OBJECTIVES: The aims of this study were to identify optimal quantitative breast magnetic resonance imaging background parenchymal enhancement (BPE) parameters associated with breast cancer risk and compare performance to qualitative assessments. METHODS: Using a matched case-control cohort of 46 high-risk women who underwent screening magnetic resonance imaging (23 who developed breast cancer matched to 23 who did not), fibroglandular tissue area, BPE area, and intensity metrics (mean, SD, quartiles, skewness, and kurtosis) were quantitatively measured at varying enhancement thresholds. Optimal thresholds for discriminating between cancer and control cohorts were identified for each metric and performance summarized using area under the receiver operating characteristic curve. RESULTS: Women who developed breast cancer exhibited greater BPE area (adjusted P = 0.004) and higher intensity statistics (adjusted P < 0.004, except skewness and kurtosis with P > 0.99) than did control subjects, with areas under the receiver operating characteristic curve ranging from 0.75 to 0.78 at optimized thresholds. CONCLUSIONS: Elevated quantitative BPE parameters, related to both area and intensity of enhancement, are associated with breast cancer development.

Temporal Variability of Escherichia coli Diversity in the Gastrointestinal Tracts of Tanzanian Children with and without Exposure to Antibiotics.

The stability of the Escherichia coli populations in the human gastrointestinal tract is not fully appreciated, and represents a significant knowledge gap regarding gastrointestinal community structure, as well as resistance to incoming pathogenic bacterial species and antibiotic treatment. The current study examines the genomic content of 240 Escherichia coli isolates from 30 children, aged 2 to 35 months old, in Tanzania. The E. coli strains were isolated from three time points spanning a six-month time period, with and without antibiotic treatment. The resulting isolates were sequenced, and the genomes compared. The findings in this study highlight the transient nature of E. coli strains in the gastrointestinal tract of these children, as during a six-month interval, no one individual contained phylogenomically related isolates at all three time points. While the majority of the isolates at any one time point were phylogenomically similar, most individuals did not contain phylogenomically similar isolates at more than two time points. Examination of global genome content, canonical E. coli virulence factors, multilocus sequence type, serotype, and antimicrobial resistance genes identified diversity even among phylogenomically similar strains. There was no apparent increase in the antimicrobial resistance gene content after antibiotic treatment. The examination of the E. coli from longitudinal samples from multiple children in Tanzania provides insight into the genomic diversity and population variability of resident E. coli within the rapidly changing environment of the gastrointestinal tract of these children.IMPORTANCE This study increases the number of resident Escherichia coli genome sequences, and explores E. coli diversity through longitudinal sampling. We investigate the genomes of E. coli isolated from human gastrointestinal tracts as part of an antibiotic treatment program among rural Tanzanian children. Phylogenomics demonstrates that resident E. coli are diverse, even within a single host. Though the E. coli isolates of the gastrointestinal community tend to be phylogenomically similar at a given time, they differed across the interrogated time points, demonstrating the variability of the members of the E. coli community in these subjects. Exposure to antibiotic treatment did not have an apparent impact on the E. coli community or the presence of resistance and virulence genes within E. coli genomes. The findings of this study highlight the variable nature of specific bacterial members of the human gastrointestinal tract.