MRI-visualized T2 hyperintense breast lesions: identifying clinical and imaging factors linked to malignant biopsy outcomes.

PURPOSE: To determine the malignancy rate for MRI-guided breast biopsies performed for T2 hyperintense breast lesions and to assess additional clinical and MRI characteristics that can predict benign and malignant outcomes. METHODS: A retrospective chart review of consecutive MRI-guided breast biopsies performed in two tertiary hospitals was conducted over two years. Biopsies performed for T2 hyperintense lesions were selected, and further lesion imaging characteristics and patient risk factors were collected. Univariate and multivariate modeling regression were used to determine additional imaging and patient factors associated with malignant outcomes for biopsies of T2 hyperintense lesions. RESULTS: Out of 369 MRI-guided breast biopsies, 100 (27%) were performed for T2 hyperintense lesions. Two biopsy-proven benign lesions were excluded as the patient was lost on follow-up. With a study cohort of 98 lesions, the final pathology results were benign for 80 (80%) of these lesions, while 18 (18%) were malignant. Using multivariate logistic modeling, patient age > 50 (OR 5.99 (1.49, 24.08 95% CI), p < 0.05) and lesion size > 3 cm (OR 5.54 (1.54-18.7), p < 0.01) were found to be important predictors of malignant outcomes for MRI biopsies performed for T2 hyperintense lesions. CONCLUSION: Our study observed a high malignancy rate, challenging the assumption that T2 hyperintensity can be considered a benign imaging characteristic for otherwise suspicious MRI-detected lesions. Decision-making regarding tissue sampling should be made based on a thorough evaluation of more reliable additional demographic and imaging factors, including patient age and lesion size.

Primary MALT lymphoma of the breast: pathological and radiological characteristics.

PURPOSE: Primary Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare diagnosis in the breast, and clinical diagnosis based on radiological features is often challenging. This study aimed to evaluate the clinicopathological, and radiological characteristics of the patients diagnosed with primary breast MALT lymphoma. METHODS: This study examined 18 cases of primary MALT lymphoma of the breast diagnosed at a single tertiary center between January 2002 to December 2020. Medical charts, radiological imaging and original pathology slides were reviewed for each case. RESULTS: All cases were female (gender assigned at birth) and presented with a palpable mass or an incidental imaging finding. Imaging presentation ranged from mammographic asymmetries, circumscribed masses, and ultrasound masses lacking suspicious features. Seventeen cases were biopsied under ultrasound; one received a diagnostic excision biopsy. Microscopic examination of the breast specimens demonstrated atypical small lymphocyte infiltration with plasmacytoid differentiation and rare lymphoepithelial lesions. Immunohistochemistry was performed in all cases and established the diagnosis. Most patients were treated with radiotherapy, and only three were treated with chemotherapy. The median follow-up period was 4 years and 7.5 months, and all patients were alive at the last follow-up. CONCLUSION: Primary MALT breast lymphomas are usually indolent and non-systemic, and local radiotherapy may effectively alleviate local symptoms. Radiological findings show overlap with benign morphological features, which can delay the diagnosis of this unusual etiology. Although further studies involving a larger cohort could help establish the clinical and radiological characteristics of primary breast MALT lymphomas, pathology remains the primary method of diagnosis. TRIAL REGISTRATION NUMBER: University Health Network Ethics Committee (CAPCR/UHN REB number 19-5844), retrospectively registered.

Evaluating persistent T1-weighted lesions without concurrent abnormal enhancement on breast MRI in neoadjuvant chemotherapy patients: implications for complete pathological response.

OBJECTIVE: This study aims to determine whether persistent T1-weighted lesions signify a complete pathological response (pCR) in breast cancer patients treated with neoadjuvant chemotherapy and surgery, and to evaluate their correlation with imaging responses on MRI. MATERIALS AND METHODS: A retrospective review was conducted on data from breast cancer patients treated between January 2011 and December 2018. Patients who underwent breast MRI and pre- and post-neoadjuvant chemotherapy followed by surgery were included. Those with distant metastasis, no planned surgery, pre-surgery radiation, ineligibility for neoadjuvant chemotherapy, or unavailable surgical pathology were excluded. Groups with and without persistent T1-weighted lesions were compared using the chi-square test for categorical variables and the Student t test or Wilcox rank sum test for continuous variables. Univariate logistic regression was used to evaluate the association of the final pathological response with the presence of T1-persistent lesion and other characteristics. RESULTS: Out of 319 patients, 294 met the inclusion criteria (breast cancer patients treated with neoadjuvant chemotherapy and subsequent surgery); 157 had persistent T1 lesions on post-chemotherapy MRI and 137 did not. A persistent T1 lesion indicated reduced likelihood of complete pathological response (14% vs. 39%, p < 0.001) and imaging response (69% vs. 93%, p < 0.001). Multivariable analysis confirmed these findings: OR 0.37 (95% CI 0.18-0.76), p = 0.007. No other characteristics correlated with T1 residual lesions. CONCLUSION: Persistent T1-weighted lesions without associated abnormal enhancement on post-treatment breast MRI correlate with lower complete pathological and imaging response rates. CLINICAL RELEVANCE STATEMENT: The study underscores the importance of persistent T1-weighted lesions on breast MRI as vital clinical markers, being inversely related to a complete pathological response following neoadjuvant chemotherapy; they should be a key factor in guiding post-neoadjuvant chemotherapy treatment decisions. KEY POINTS: • Persistent T1 lesions on post-chemotherapy breast MRI indicate a reduced likelihood of achieving a complete pathological response (14% vs. 39%, p < 0.001) and imaging response (69% vs. 93%, p < 0.001). • Through multivariable analysis, it was confirmed that the presence of a persistent T1 lesion on breast MRI post-chemotherapy is linked to a decreased likelihood of complete pathological response, with an odds ratio (OR) of 0.37 (95% CI 0.18-0.76; p = 0.007). • In addition to the convention of equating the absence of residual enhancement to complete imaging response, our results suggest that the presence or absence of residual T1 lesions should also be considered.

Breast Magnetic Resonance Imaging for Preoperative Evaluation of Breast Cancer: A Systematic Review and Meta-Analysis.

Purpose: Preoperative breast magnetic resonance imaging (MRI) is known to detect additional cancers that are occult on mammography and ultrasound. There is debate as to whether these additional lesions affect clinical outcomes. The objective of this systematic review was to summarize the evidence on whether additional information on disease extent obtained with preoperative breast MRI in patients with newly diagnosed breast cancer affects surgical management, rates of recurrence, survival, re-excision, and early detection of bilateral cancer. Methods: Embase, MEDLINE, and Cochrane Central Register of Controlled Trials were searched until January 2021 (partial update July 2022) for studies comparing outcomes with versus without pre-operative MRI. Included were both randomized controlled trials and other comparative studies provided MRI and control groups had equivalent disease and patient characteristics or methods such as multivariable analysis or propensity score matching were used to control potential confounders. Results: The search resulted in 26,399 citations, of which 8 randomized control trials, 1 prospective cohort study, and 42 retrospective studies met the inclusion criteria. Use of MRI resulted in decreased rates of reoperations (OR = 0.73, 95% CI = 0.63 to 0.85), re-excisions (OR = 0.63, 95% CI = 0.45 to 0.89), and recurrence (HR = 0.77, 95% CI = 0.65 to 0.90). Increased detection of synchronous contralateral breast cancers led to a reduction in metachronous contralateral breast cancer (HR = 0.71, 95% CI = 0.59 to 0.85). Hazard ratios for recurrence-free and overall survival were 0.77 (95% CI = 0.53 to 1.12) and 0.89 (95% CI = 0.74 to 1.07). Conclusion: This systematic review indicates substantial benefits of pre-operative breast MRI in decreasing reoperations and recurrence.

Decoding the Prevalent High-Risk Breast Cancers: Demographics, Pathological, Imaging Insights, and Long-Term Outcome.

Objective: To investigate the features and outcomes of breast cancer in high-risk subgroups. Materials and Methods: REB approved an observational study of women diagnosed with breast cancer from 2010 to 2019. Three radiologists, using the BI-RADS lexicon, blindly reviewed mammogram and MRI screenings without a washout period. Consensus was reached with 2 additional reviewers. Inter-rater agreement was measured by Fleiss Kappa. Statistical analysis included Mann-Whitney U, Chi-square tests for cohort analysis, and Kaplan-Meier for survival rates, with a Cox model for comparative analysis using gene mutation as a reference. Results: The study included 140 high-risk women, finding 155 malignant lesions. Significant age differences noted: chest radiation therapy (median age 44, IQR: 37.0-46.2), gene mutation (median age 49, IQR: 39.8-58.0), and familial risk (median age 51, IQR: 44.5-56.0) (P = .007). Gene mutation carriers had smaller (P = .01), higher-grade tumours (P = .002), and more triple-negative ER- (P = .02), PR- (P = .002), and HER2- (P = .02) cases. MRI outperformed mammography in all subgroups. Substantial to near-perfect inter-rater agreement observed. Over 10 years, no deaths occurred in chest radiation group, with no significant survival difference between gene mutation and familial risk groups, HR = 0.93 (95% CI: 0.27, 3.26), P = .92. Conclusion: The study highlights the importance of age and specific tumour characteristics in identifying high-risk breast cancer subgroups. MRI is confirmed as an effective screening tool. Despite the aggressive nature of cancers in gene mutation carriers, early detection is crucial for survival outcomes. These insights, while necessitating further validation with larger studies, advocate for a move toward personalized medical care, strengthening the existing healthcare guidelines.

False-positive incidental lesions detected on contrast-enhanced breast MRI: clinical and imaging features.

PURPOSE: To identify demographic and imaging features of MRI-detected enhancing lesions without clinical, ultrasound, and mammographic correlation associated with false-positive outcomes, impacting patient care. MATERIALS AND METHODS: A retrospective multi-institutional study of imaging studies and patient's chart review of consecutive women with MRI-detected enhancing lesions without clinical, mammogram, or ultrasound correlation between January and December 2018, who underwent MRI-guided biopsy. According to the BI-RADS lexicon, lesions' frequency and imaging features were recorded. The demographic and imaging characteristics variables were correlated with histopathology as the gold standard and an uneventful follow-up of at least one year. Univariate logistic regression analysis was used to explore the correlation between the baseline variables such as age, genetic mutation, family history of breast cancer, personal history of breast cancer, MRI indication, background parenchymal enhancement, and MRI characteristic of the lesion with the false-positive results in main data and subgroup analysis. RESULTS: Two hundred nineteen women (median age 49 years; range 26-85 years) with 219 MRI-detected enhancing lesions that underwent MRI-guided vacuum-assisted biopsy during the study period fulfilled the study criteria and formed the study cohort. Out of 219, 180 lesions (82.2%) yielded benign pathology results, including 137 benign outcomes (76%) and 43 high-risk lesions (24%). Most demographic and imaging characteristics variables did not help to differentiate malignant from benign lesions. The variables that showed statistically significant association with true-positive results in univariate analyses were age (OR 1.05; 95% CI 1.02-1.08; p = 0.0015), irregular mass-lesion shape when compared with oval/round mass lesion (OR 11.2; 95% CI 1.6-78.4; p = 0.015), and clumped and clustered ring of enhancement when compared with homogeneous (OR 3.22, 95% CI 1.40-7.40; p = 0.0058). For participants with mass breast lesion, the hyperintense signal on the T2-weighted sequence (compared to the normal fibroglandular signal) was significantly related to the false-positive result (OR 0.13; 95% CI 0.02-0.76; p = 0.024). CONCLUSION: Young patients, oval/round mass-lesion shape, and homogeneous pattern of non-mass enhancement showed the strongest association with false-positive results of enhancing lesions depicted by MRI. For participants with mass breast lesion, T2-bright mass lesion showed significant association with false-positive result. It may impact the patient's management with a suggestion of follow-up rather than interventional procedure when these demographic and imaging parameters are present, consequently decreasing the patient's anxiety and health care costs.

Supplemental Breast Cancer Screening in Women with Dense Breasts and Negative Mammography: A Systematic Review and Meta-Analysis.

Background The best supplemental breast cancer screening modality in women at average risk or intermediate risk for breast cancer with dense breast and negative mammogram remains to be determined. Purpose To conduct systematic review and meta-analysis comparing clinical outcomes of the most common available supplemental screening modalities in women at average risk or intermediate risk for breast cancer in patients with dense breasts and mammography with negative findings. Materials and Methods A comprehensive search was conducted until March 12, 2020, in Medline, Epub Ahead of Print and In-Process and Other Non-Indexed Citations; Embase Classic and Embase; Cochrane Central Register of Controlled Trials; and Cochrane Database of Systematic Reviews, for Randomized Controlled Trials and Prospective Observational Studies. Incremental cancer detection rate (CDR); positive predictive value of recall (PPV1); positive predictive value of biopsies performed (PPV3); and interval CDRs of supplemental imaging modalities, digital breast tomosynthesis, handheld US, automated breast US, and MRI in non-high-risk patients with dense breasts and mammography negative for cancer were reviewed. Data metrics and risk of bias were assessed. Random-effects meta-analysis and two-sided metaregression analyses comparing each imaging modality metrics were performed (PROSPERO; CRD42018080402). Results Twenty-two studies reporting 261 233 screened patients were included. Of 132 166 screened patients with dense breast and mammography negative for cancer who met inclusion criteria, a total of 541 cancers missed at mammography were detected with these supplemental modalities. Metaregression models showed that MRI was superior to other supplemental modalities in CDR (incremental CDR, 1.52 per 1000 screenings; 95% CI: 0.74, 2.33; P < .001), including invasive CDR (invasive CDR, 1.31 per 1000 screenings; 95% CI: 0.57, 2.06; P < .001), and in situ disease (rate of ductal carcinoma in situ, 1.91 per 1000 screenings; 95% CI: 0.10, 3.72; P < .04). No differences in PPV1 and PPV3 were identified. The limited number of studies prevented assessment of interval cancer metrics. Excluding MRI, no statistically significant difference in any metrics were identified among the remaining imaging modalities. Conclusion The pooled data showed that MRI was the best supplemental imaging modality in women at average risk or intermediate risk for breast cancer with dense breasts and mammography negative for cancer. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Hooley and Butler in this issue.

Canadian Association of Radiologists Breast Disease Imaging Referral Guideline.

The Canadian Association of Radiologists (CAR) Breast Disease Expert Panel consists of breast imaging radiologists, a high-risk breast clinician, a patient advisor, and an epidemiologist/guideline methodologist. After developing a list of 20 clinical/diagnostic scenarios, a systematic rapid scoping review was undertaken to identify systematically produced referral guidelines that provide recommendations for one or more of these clinical/diagnostic scenarios. Recommendations from 30 guidelines and contextualization criteria in the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) for guidelines framework were used to develop 69 recommendation statements across the 20 scenarios. This guideline presents the methods of development and the recommendations for referring asymptomatic individuals, symptomatic patients, and other scenarios requiring imaging of the breast.

Contralateral Breast Screening with Preoperative MRI: Long-Term Outcomes for Newly Diagnosed Breast Cancer.

Background The diagnostic value of screening the contralateral breast with MRI in patients with newly diagnosed breast cancer is poorly understood. Purpose To assess the impact of MRI for screening the contralateral breast on long-term outcomes in patients with newly diagnosed breast cancer and to determine whether subgroups with unfavorable prognoses would benefit from MRI in terms of survival. Materials and Methods Data on consecutive patients with newly diagnosed breast cancer seen from January 2008 to December 2010 were reviewed retrospectively. Patients with neoadjuvant chemotherapy, previous breast cancer, distant metastasis, absence of contralateral mammography at diagnosis, and no planned surgical treatment were excluded. Groups that did and did not undergo preoperative MRI were compared. Survival analysis was performed using the Kaplan-Meier method for propensity score-matched groups to estimate cause-specific survival (CSS) and overall survival (OS). A marginal Cox proportional hazards model was used to evaluate association of MRI and clinicopathologic variables with OS. Results Of 1846 patients, 1199 fulfilled the inclusion criteria. Median follow-up time was 10 years (range, 0-14 years). The 2:1 matched sample comprised 705 patients (470 in the MRI group and 235 in the no-MRI group); median ages at surgery were 59 years (range, 31-87 years) and 64 years (range, 37-92 years), respectively. MRI depicted contralateral synchronous disease more frequently (27 of 470 patients [5.7%] vs five of 235 patients [2.1%]; P = .047) and was associated with a higher OS (hazard ratio [HR], 2.51; 95% CI: 1.25, 5.06; P = .01). No differences were observed between groups in metachronous disease rate (MRI group: 21 of 470 patients [4.5%]; no-MRI group: 10 of 235 patients [4.3%]; P > .99) or CSS (HR, 1.34; 95% CI: 0.56, 3.21; P = .51). MRI benefit was greater in patients with larger tumor sizes (>2 cm) (HR, 2.58; 95% CI: 1.11, 5.99; P = .03) and histologic grade III tumors (HR, 2.94; 95% CI: 1.18, 7.32; P = .02). Conclusion Routine MRI screening of the contralateral breast after first diagnosis of breast cancer improved overall survival; the most pronounced benefit was found in patients with larger primary tumor size and primary tumors of histologic grade III. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Taourel in this issue.

Digital Breast Tomosynthesis: Potential Benefits in Routine Clinical Practice.

Digital breast tomosynthesis (DBT) is gradually being implemented in routine clinical breast imaging practice. The technique of image acquisition reduces the confounding effect of overlapping breast tissue, which substantially affects cancer detection, abnormal recall, and interval cancer rates in a screening/ surveillance setting. In a diagnostic setting, tomosynthesis also allows for improved lesion localization and characterization over conventional imaging, which potentially improves the accuracy and improved workflow efficiency. To optimize the utility of tomosynthesis, imagers should be aware of the pertinent aspects of image acquisition as it relates to interpretation, the appearance of benign and malignant pathologies, and sources of possible misinterpretation. This article aims to provide a practical knowledge base of DBT and demonstrate its potential benefits when incorporated into routine clinical practice.

Factors Influencing Trainees' Interest in Breast Imaging.

Purpose: To gauge the level of interest in breast imaging (BI) and determine factors impacting trainees' decision to pursue this subspecialty. Methods: Canadian radiology residents and medical students were surveyed from November 2020 to February 2021. Training level, actual vs preferred timing of breast rotations, fellowship choices, perceptions of BI, and how artificial intelligence (AI) will impact BI were collected. Chi-square, Fisher's exact tests and univariate logistic regression were performed to determine the impact of trainees' perceptions on interest in pursuing BI/women's imaging (WI) fellowships. Results: 157 responses from 80 radiology residents and 77 medical students were collected. The top 3 fellowship subspecialties desired by residents were BI/WI (36%), abdominal imaging (35%), and interventional radiology (25%). Twenty-five percent of the medical students were unsure due to lack of exposure. The most common reason that trainees found BI unappealing was repetitiveness (20%), which was associated with lack of interest in BI/WI fellowships (OR = 3.9, 95% CI: 1.6-9.5, P = .002). The most common reason residents found BI appealing was procedures (59%), which was associated with interest in BI/WI fellowships (OR, 3.2, 95% CI, 1.2-8.6, P = .02). Forty percent of residents reported an earlier start of their first breast rotation (PGY1-2) would affect their fellowship choice. Conclusion: This study assessed the current level of Canadian trainees' interest in BI and identified factors that influenced their decisions to pursue BI. Solutions for increased interest include earlier exposure to breast radiology and addressing inadequacies in residency training.

The characteristics associated with upgrade on surgical pathology of conventional imaging occult DCIS diagnosed by MRI.

PURPOSE: To characterize the clinical, pathological, and imaging features of DCIS occult on conventional imaging diagnosed on MRI-guided biopsy associated with increased risk of invasive disease on surgical excision. MATERIALS AND METHODS: All consecutive patients with MRI-detected DCIS occult on conventional imaging between January 2009 and December 2018 were included. Women were divided into two groups based on final pathology: Pure DCIS or DCIS with invasive component. Clinical, imaging, and pathological risk factors for upgrade to invasion were evaluated. RESULTS: Of 50 patients who met the inclusion criteria, 12 (24%) were upgraded to invasive malignancy in the final pathology. The only parameters that showed statistically significant association with upgrade were related to kinetic characteristics: 53% of patients with the combination of fast early upstroke and either plateau or washout curve were upgraded, compared to 12% of women without this combination (p = 0.006). The sensitivity of combined kinetic features for predicting upgrade was 67% (95% CI 35-90%), specificity was 84% (CI 95% 68-94%), positive predictive value was 57% (CI 95% 37-75%), negative predictive value was 89% (CI 95% 77-95%), and OR was 78% (64-88%). CONCLUSION: Kinetic characteristics show the strongest association with upgrade to invasion in DCIS occult on mammogram and US. Larger studies should be encouraged to consolidate our findings, which may have implication for treatment planning.

Lobular neoplasia occult on conventional imaging and diagnosed on MRI-guided biopsy: can we estimate upgrade on surgical pathology?

PURPOSE: The goal of this study is to evaluate the frequency and imaging features of lobular neoplasia (LN) diagnosed on MRI-guided biopsy, determine the upgrade rate to malignancy, and assess for any features that may be associated with an upgrade on surgical excision. MATERIALS AND METHODS: Research ethical board approved the review of consecutive patients with MRI-detected LN between January 2009 and December 2018 with differentiation between pure LN and LN with associated other high-risk lesions. The final outcome was determined by final pathology results from surgical excision or 24 months of follow-up. Appropriate statistical tests were used. RESULTS: Out of 1250 MRI-guided biopsies performed, 76 lesions (6%) fulfilled the inclusion criteria and formed the study cohort. Of the 76 lesions, 54 (71%) were pure LN while the rest had coexistent high-risk lesion. Non-mass enhancement (NME) was the most common lesion type (62, 82%). Fifty-nine lesions (78%) were surgically excised, the other 17 had benign follow-up. Overall, 8 lesions (11%) were upgraded to malignancy on final pathology. Malignant outcome was associated with larger lesion size (5.5 versus 1.9 cm, P < 0.001) and a clumped NME pattern (75% versus 24%, P = 0.006). Lesion size and clumped NME remained significantly associated with upgrade on sub-analysis of the pure LN group. CONCLUSION: Larger lesion size and clumped NME are imaging findings associated with upgrade of LN diagnosed by MRI-guided biopsy. This may influence patient management in this clinical setting. Additional larger studies are needed to consolidate our results and to potentially detect additional factors associated with upgrade.

Can breast MRI accurately exclude malignancy in mammographic architectural distortion?

OBJECTIVES: To investigate the diagnostic accuracy of problem-solving breast magnetic resonance imaging (MRI) in excluding malignancy in a cohort of patients diagnosed with mammographic architectural distortion (MAD). METHODS: The Institutional Review Board approved the study. Imaging database with 40,245 breast MRIs done between January 2008 and September 2018 was retrospectively reviewed. The study included all exams considered problem-solving MRI for MAD. Two radiologists reviewed the imaging data. Outcome was determined by the pathology results of biopsy/surgical excision or at least 1 year of clinical and radiological follow-up. Predictors for malignancy were examined, and appropriate statistical tests were applied. RESULTS: One hundred seventy-five patients (median age 53 years) fulfilled the inclusion criteria and formed the study cohort. No cancers were diagnosed in 106 patients with a negative MRI. Out of 69 women with positive MRI findings, 48 (70%) had benign outcome defined either by pathology result or by negative follow-up, and 21 (30%) yielded malignancy. Malignancy was significantly associated with positive MRI (p < 0.001) and older age (p = 0.014). Falsely positive MRIs were frequently found in women with radial scars. The sensitivity, specificity, negative predictive value, positive predictive value, and overall accuracy of breast MRI were 100% (95% CI 84 to 100%), 68% (CI 61 to 76%), 100% (CI 95 to 100%), 30% (CI 26 to 36%), and 73% (95% CI 66-79), respectively. CONCLUSION: A negative breast MRI in patients with MAD was reliable in excluding malignancy in this cohort and may have a role as a precision medicine tool for avoiding unnecessary interventions. KEY POINTS: • MRI shows a high negative predictive value in MAD cases. • MRI displays low accuracy in differentiating malignancy from RS. • MRI is a reliable non-invasive method to exclude malignancy in women with mammographic architectural distortion, potentially avoiding unnecessary biopsies and surgeries.

Cellular fibroepithelial lesions diagnosed on core needle biopsy: Is there any role of clinical-sonography features helping to differentiate fibroadenomas and phyllodes tumor?

OBJECTIVE: The purpose of this study is to determine the role of clinico-sonographic features of breast cellular fibroepithelial lesions (CFELs) diagnosed on core needle biopsy (CNB) in the differentiation between fibroadenoma (FA) and phyllodes. MATERIALS AND METHODS: Results of consecutive women with a CNB showing CFEL from 2005 to 2010 were retrospectively reviewed. Clinical and sonographic findings were compared with surgical outcomes. Chi-square and Fisher's exact tests were used followed by a regression model for statistical analysis. RESULTS: A total of 131 women with 134 CFEL were included in the study; 89 (66%) were FAs and 45 (34%) were phyllodes (32 benign; 13 malignant). Significant predictors of increased risk of phyllodes tumor were patient age equal to or greater than 50 years (P = .021) and lesion size less than 2 cm at sonography (P = .043). No other imaging or clinical features were able to differentiate FA from phyllodes tumors. CONCLUSION: CFEL with a larger size in older women is associated with the surgical pathological result of phyllodes tumor and management should be tailored accordingly. Younger patients with small size nodules might be approached less aggressively, depending on a personalized discussion with the surgeons, taking into account the results obtained in this study.

COVID-19: Safe Guidelines for Breast Imaging During the Pandemic.

During the COVID-19 pandemic, breast imaging must be performed using safe practices. Balancing the need to avoid delays in the diagnosis of breast cancer while avoiding infection requires careful attention to personal protective equipment and physical distancing and vigilance to maintain these practices. The Canadian Society of Breast Imaging/Canadian Association of Radiologists guideline for breast imaging during COVID-19 is provided based on priority according to risk of breast cancer and impact of delaying treatment. A review of the best practices is presented that allow breast imaging during COVID-19 to maximize protection of patients, technologists, residents, fellows, and radiologists and minimize spread of the infection. The collateral damage of delaying diagnosis of breast cancer due to COVID-19 should be avoided when possible.

Physiological Regulation of Drug Metabolism and Transport: Pregnancy, Microbiome, Inflammation, Infection, and Fasting.

This article is a report on a symposium entitled "Physiological Regulation of Drug Metabolism and Transport" sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 2017 meeting in Chicago, IL. The contributions of physiologic and pathophysiological regulation of drug-metabolizing enzymes and transporters to interindividual variability in drug metabolism are increasingly recognized but in many cases are not well understood. The presentations herein discuss the phenomenology, consequences, and mechanism of such regulation. CYP2D6 transgenic mice were used to provide insights into the mechanism of regulation of this enzyme in pregnancy, via hepatocyte nuclear factor 4α, small heterodimer partner, and retinoids. Regulation of intestinal and hepatic drug-processing enzymes by the intestinal microbiota via tryptophan and its metabolites was investigated. The potential impact of parasitic infections on human drug metabolism and clearance was assessed in mice infected with Schistosoma mansoni or Plasmodium chabaudi chabaudi AS, both of which produced widespread and profound effects on murine hepatic drug-metabolizing enzymes. Finally, the induction of Abcc drug efflux transporters by fasting was investigated. This was demonstrated to occur via a cAMP, protein kinase A/nuclear factor-E2-related factor 2/Sirtuin 1 pathway via antioxidant response elements on the Abcc genes.

Evaluation of the Utility of Screening Mammography for High-Risk Women Undergoing Screening Breast MR Imaging.

Purpose To evaluate the value of mammography in detecting breast cancer in high-risk women undergoing screening breast magnetic resonance (MR) imaging. Materials and Methods An ethics-approved, retrospective review of prospective databases was performed to identify outcomes of 3934 screening studies (1977 screening MR imaging examinations and 1957 screening mammograms) performed between January 2012 and July 2014 in 1249 high-risk women. Performance measures including recall and cancer detection rates, sensitivity, specificity, and positive predictive values were calculated for both mammography and MR imaging. Results A total of 45 cancers (33 invasive and 12 ductal carcinomas in situ) were diagnosed, 43 were seen with MR imaging and 14 with both mammography and MR imaging. Additional tests (further imaging and/or biopsy) were recommended in 461 screening MR imaging studies (recall rate, 23.3%; 95% confidence interval [CI]: 21.5%, 25.2%), and mammography recalled 217 (recall rate, 11.1%; 95% CI: 9.7%, 12.6%). The cancer detection rate for MR imaging was 21.8 cancers per 1000 examinations (95% CI: 15.78, 29.19) and that for mammography was 7.2 cancers per 1000 examinations (95% CI: 3.92, 11.97; P < .001). Sensitivity and specificity of MR imaging were 96% and 78% respectively, and those of mammography were 31% and 89%, respectively (P < .001). Positive predictive value for MR imaging recalls was 9.3% (95% CI: 6.83%, 12.36%) and that for mammography recalls was 6.5% (95% CI: 3.57%, 10.59%). Conclusion Contemporaneous screening mammography did not have added value in detection of breast cancer for women who undergo screening MR imaging. Routine use of screening mammography in women undergoing screening breast MR imaging warrants reconsideration. © RSNA, 2017 Online supplemental material is available for this article.

Sirtuin 1 activation alleviates cholestatic liver injury in a cholic acid-fed mouse model of cholestasis.

Sirtuin1 (Sirt1; mammalian homolog of Saccharomyces cerevisiae enzyme Sir2) is a transcriptional and transactivational regulator of murine farnesoid X receptor (Fxr), which is the primary bile acid (BA) sensor, and critical regulator of BA metabolism in physiological and pathophysiological conditions. Previous studies have suggested compromised Sirt1 expression in rodent models of cholestatic liver injury. We hypothesized that Sirt1 could be potentially targeted to alleviate cholestatic liver injury. In cultured primary human hepatocytes, SIRT1 messenger RNA was down-regulated after GCA treatment, potentially through induction of microRNA (miR)-34a, whereas tauroursodeoxycholic acid induced SIRT1 expression without affecting miR-34a expression. Sirt1 expression was also significantly down-regulated in three mouse models of liver injury (bile duct ligation, 1% cholic acid [CA] fed, and the Mdr2-/- mouse). Mice fed CA diet also demonstrated hepatic FXR hyperacetylation and induction of the Janus kinase/p53 pathway. Mice fed a CA diet and concurrently administered the Sirt1 activator, SRT1720 (50 mg/kg/day, orally), demonstrated 40% and 45% decrease in plasma alanine aminotransferase and BA levels, respectively. SRT1720 increased hepatic BA hydrophilicity by increasing tri- and tetrahydroxylated and decreasing the dihydroxylated BA fraction. SRT1720 administration also inhibited hepatic BA synthesis, potentially through ileal fibroblast growth factor 15- and Fxr-mediated inhibition of cytochrome p450 (Cyp) 7a1 and Cyp27a1, along with increased hepatic BA hydroxylation in association with Cyp2b10 induction. SRT1720 administration significantly induced renal multidrug resistance-associated protein 2 and 4, peroxisome proliferator-activated receptor gamma coactivator 1-α, and constitutive androstance receptor expression along with ∼2-fold increase in urinary BA concentrations. CONCLUSION: SRT1720 administration alleviates cholestatic liver injury in mice by increasing hydrophilicity of hepatic BA composition and decreasing plasma BA concentration through increased BA excretion into urine. Thus, use of small-molecule activators of Sirt1 presents a novel therapeutic target for cholestatic liver injury. (Hepatology 2016;64:2151-2164).

Do Tumor Necrosis Factor (TNF) Inhibitors Improve the Glycemic Control in Patients with Rheumatoid Arthritis and Concomitant Diabetes Mellitus?

Inflammation and insulin resistance are closely linked to each other. Inflammatory rheumatic diseases including rheumatoid arthritis (RA) are associated with increased insulin resistance and reduced insulin sensitivity by virtue of proinflammatory cytokines, mainly tumor necrosis factor alpha (TNF-α). TNF inhibitors have been shown to improve the insulin sensitivity and reduce the risk of incident diabetes in patients with RA. We hypothesize that TNF inhibitors may improve the glycemic control in patients with concomitant RA and diabetes mellitus.