Experience of a single healthcare system with screening mammography before and after COVID-19 shutdown.

PURPOSE: To evaluate COVID-19's longitudinal impact on screening mammography volume trends. METHODS: HIPAA-compliant, IRB-approved, single institution, retrospective study of screening mammogram volumes before (10/21/2016-3/16/2020) and greater than two years after (6/17/2020-11/30/2022) a state-mandated COVID-19 shutdown (3/17/2020-6/16/2020) were reviewed. A segmented quasi-poisson linear regression model adjusting for seasonality and network and regional population growth compared volume trends before and after the shutdown of each variable: age, race, language, financial source, risk factor for severe COVID-19, and examination location. RESULTS: Adjusted model demonstrated an overall increase of 65 screening mammograms per month before versus a persistent decrease of 5 mammograms per month for >2 years after the shutdown (p < 0.0001). In subgroup analysis, downward volume trends were noted in all age groups <70 years (age < 50: +9/month before vs. -7/month after shutdown; age 50-60: +17 vs. -7; and age 60-70: +21 vs. -2; all p < 0.001), those identifying as White (+55 vs. -8, p < 0.0001) and Black (+4 vs. +1, p = 0.009), all financial sources (Medicare: +22 vs. -3, p < 0.0001; Medicaid: +5 vs. +2, p = 0.006; private insurance/self-pay: +38 vs. -4, p < 0.0001), women with at least one risk factor for severe COVID-19 (+30 vs. -48, p < 0.0001), and screening mammograms performed at a hospital-based location (+48 vs. -14, p = 0.0001). CONCLUSION: The screening mammogram volume trend more than two years after the COVID-19 shutdown has continued to decline for most patient populations. Findings highlight the need to identify additional areas for education and outreach.

Audit of Prior Screening Mammograms of Screen-Detected Cancers: Implications for the Delay in Breast Cancer Detection.

When cancer is detected in a screening mammogram, on occasion retrospective review of prior screening (pre-index) mammograms indicates a likely presence of cancer. These missed cancers during pre-index screens constitute a delay in detection and diagnosis. This study was undertaken to quantify the missed cancer rate by auditing pre-index screens to improve the quality of mammography screening practice. From a cohort of 135 screen-detected cancers, 120 pre-index screening mammograms could be retrieved and served as the study sample. A consensus read by 2 radiologists who interpreted the pre-index screens in an unblinded manner with full knowledge of cancer location, cancer type, lesion type, and pathology served as the truth or reference standard. Five radiologists interpreted the pre-index screens in a blinded manner. Established performance metrics such as sensitivity and specificity were quantified for each reader in interpreting these pre-index screens in a blinded manner. All five radiologists detected lesions in 8/120 (6.7%) screens. Excluding the 2 readers whose performance was close to random, all the 3 remaining readers detected lesions in 13 pre-index screens. This indicates that there is a delay in diagnosis by at least one cycle from 8/120 (6.7%) to 13/120 (10.8%). There were no observable trends in terms of either the cancer type or the lesion type. Auditing prior screening mammograms in screen-detected cancers can help in identifying the proportion of cases that were missed during interpretation and help in quantifying the delay in breast cancer detection.

Electronic Worklist Improves Timeliness of Screening Mammogram Interpretation in an Urban Underserved Population.

OBJECTIVES: To evaluate the impact of an electronic workflow update on screening mammography turnaround time and time to diagnostic imaging for mammography performed on our urban mobile mammography van and at an urban community health center. METHOD: Prior to 10/15/2019, screening exams for the mammography van and urban community health center were made available for interpretation to a single designated radiologist via a manually generated paper list. On 10/15/2019, screening exams were routed electronically onto PACS for any breast radiologist across our Network to interpret. Screening mammogram turnaround time (defined as time form image acquisition to report finalization), time to diagnostic imaging, and time to tissue sampling were collected for pre- and post-implementation periods (6/1-9/30/2019 and 11/1/2019-2/29/2020, respectively) and compared via student t-test and statistical process control analyses. RESULTS: The number of screening exams in the pre- and post-implementation periods were 851 and 728 exams, respectively. Patients were predominately Black and/or African American (400/1579, 25%), non-English speaking (858/1579, 54%) and insured by Medicaid (751/1579, 48%). After implementation of the electronic workflow, turnaround time decreased from 101.0 to 36.4 hours (63.9%, P <0.001) and statistical process control analyses showed sustained decrease in mean turnaround time. However, mean time to diagnostic imaging and tissue sampling were unchanged after implementation (39 vs 45, days; P = 0.330 and 43 vs 59; P = 0.187, respectively). CONCLUSION: Electronic workflow management can reduce screening mammography turnaround time for underserved populations, but additional efforts are warranted to improve time to imaging follow-up for abnormal screening mammograms.

Patients characteristics related to screening mammography cancellation and rescheduling rates during the COVID-19 pandemic.

PURPOSE: To identify patient characteristics associated with screening mammography cancellations and rescheduling during the COVID-19 pandemic. METHODS: Scheduled screening mammograms during three time periods were retrospectively reviewed: state-mandated shutdown (3/17/2020-6/16/2020) during which screening mammography was cancelled, a period of 2 months immediately after screening mammography resumed (6/17/2020-8/16/2020), and a representative period prior to COVID-19 (6/17/2019-8/16/2019). Relative risk of cancellation before COVID-19 and after reopening was compared for age, race/ethnicity, insurance, history of chronic disease, and exam location, controlling for other collected variables. Risk of failure to reschedule was similarly compared between all 3 time periods. RESULTS: Overall cancellation rate after reopening was higher than before shutdown (7663/16595, 46% vs 5807/15792, 37%; p < 0.001). Relative risk of cancellation after reopening increased with age (1.20 vs 1.27 vs 1.36 for ages at 25th, 50th, and 75th quartile or 53, 61, and 70 years, respectively, p < 0.001). Relative risk of cancellation was also higher among Medicare patients (1.41) compared to Medicaid and those with other providers (1.26 and 1.21, respectively, p < 0.001) and non-whites compared to whites (1.34 vs 1.25, p = 0.03). Rescheduling rate during shutdown was higher than before COVID-19 and after reopening for all patients (10,658/13593, 78%, 3569/5807, 61%, and 4243/7663, respectively, 55%, p < 0.001). Relative risk of failure to reschedule missed mammogram was higher in hospitals compared to outpatient settings both during shutdown and after reopening (0.62 vs 0.54, p = 0.005 and 1.29 vs 1.03, p < 0.001, respectively). CONCLUSION: Minority race/ethnicity, Medicare insurance, and advanced age were associated with increased risk of screening mammogram cancellation during COVID-19.

Diffusion-weighted MRI for Unenhanced Breast Cancer Screening.

Diffusion-weighted (DW) MRI is a rapid technique that measures the mobility of water molecules within tissue, reflecting the cellular microenvironment. At DW MRI, breast cancers typically exhibit reduced diffusivity and appear hyperintense to surrounding tissues. On the basis of this characteristic, DW MRI may offer an unenhanced method to detect breast cancer without the costs and safety concerns associated with dynamic contrast material-enhanced MRI, the current reference standard in the setting of high-risk screening. This application of DW MRI has not been widely explored but is particularly timely given the growing health concerns related to the long-term use of gadolinium-based contrast material. Moreover, increasing breast density notification legislation across the United States is raising awareness of the limitations of mammography in women with dense breasts, emphasizing the need for additional cost-effective supplemental screening examinations. Preliminary studies suggest unenhanced MRI with DW MRI may provide higher sensitivity than screening mammography for the detection of breast malignancies. Larger prospective multicenter trials are needed to validate single-center findings and assess the performance of DW MRI for generalized breast cancer screening. Standardization of DW MRI acquisition and interpretation is essential to ensure reliable sensitivity and specificity, and an optimal approach for screening using readily available techniques is proposed here.

Diffusion-weighted MRI characteristics associated with prognostic pathological factors and recurrence risk in invasive ER+/HER2- breast cancers.

BACKGROUND: Hormone receptor-positive breast cancer is the most common subtype; better tools to identify which patients in this group would derive clear benefit from chemotherapy are needed. PURPOSE: To evaluate the prognostic potential of diffusion-weighted MRI (DWI) by investigating associations with pathologic biomarkers and a genomic assay for 10-year recurrence risk. STUDY TYPE: Retrospective. SUBJECTS: In all, 107 consecutive patients (from 2/2010 to 1/2013) with estrogen receptor (ER)-positive/HER2neu-negative invasive breast cancer who had the 21-gene recurrence score (RS) test (Oncotype DX, Genomic Health). FIELD STRENGTH/SEQUENCE: Each subject underwent presurgical 3T breast MRI, which included DWI (b = 0, 800 s/mm2 ). ASSESSMENT: Apparent diffusion coefficient (ADC) and contrast-to-noise ratio (CNR) were measured for each lesion by a fifth year radiology resident. Pathological markers (Nottingham histologic grade, Ki-67, RS) were determined from pathology reports. Medical records were reviewed to assess recurrence-free survival. STATISTICAL TESTS: RS was stratified into low (<18), moderate (18-30), and high (>30)-risk groups. Associations of DWI characteristics with pathologic biomarkers were evaluated by binary or ordinal logistic regression, as appropriate, with adjustment for multiple comparisons. Post-hoc comparisons between specific groups were also performed. RESULTS: ADCmean (odds ratio [OR] = 0.61 per 1 standard deviation [SD] increase, adj. P = 0.044) and CNR (OR = 1.76 per 1-SD increase, adj. P = 0.026) were significantly associated with increasing tumor grade. DWI CNR was also significantly associated with a high (Ki-67 ≥14%) proliferation rate (OR = 2.55 per 1-SD increase, adj. P = 0.026). While there were no statistically significant linear associations in ADC (adj. P = 0.80-0.85) and CNR (adj. P = 0.56) across all three RS groups by ordinal logistic regression, post-hoc analyses suggested that high RS lesions exhibited lower ADCmean (P = 0.037) and ADCmax (P = 0.004) values and higher CNR (P = 0.008) compared to lesions with a low or moderate RS. DATA CONCLUSION: DWI characteristics correlated with tumor grade, proliferation index, and RS, and may potentially help to identify those with highest recurrence risk and most potential benefit from chemotherapy. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage 3 J. Magn. Reson. Imaging 2017.

Visibility of mammographically occult breast cancer on diffusion-weighted MRI versus ultrasound.

PURPOSE: To investigate the visibility of mammographically occult breast cancers on diffusion-weighted MRI (DWI) versus ultrasound. MATERIALS AND METHODS: Mammographically occult breast cancers (n=60) initially detected on contrast-enhanced MRI that underwent pre-biopsy targeted ultrasound were retrospectively evaluated for visibility on DWI and ultrasound. RESULTS: More cancers were visible on DWI than ultrasound (78% vs. 63%; p=0.049), with 32 (53%) visible on both and 7 (12%) not visible on either. Visibility differences were more significant in larger lesions (92% vs. 68%, p=0.006). CONCLUSION: DWI may detect more mammographically occult cancers than ultrasound, warranting further investigation as an alternative supplemental screening technique.

DWI in the Assessment of Breast Lesions.

Diffusion-weighted imaging (DWI) holds promise to address some of the shortcomings of routine clinical breast magnetic resonance imaging (MRI) and to expand the capabilities of imaging in breast cancer management. DWI reflects tissue microstructure, and provides unique information to aid in characterization of breast lesions. Potential benefits under investigation include improving diagnostic accuracy and guiding treatment decisions. As a result, DWI is increasingly being incorporated into breast MRI protocols and multicenter trials are underway to validate single-institution findings and to establish clinical guidelines. Advancements in DWI acquisition and modeling approaches are helping to improve image quality and extract additional biologic information from breast DWI scans, which may extend diagnostic and prognostic value.

Screening Mammography: Patient Perceptions and Preferences Regarding Communication of Estimated Breast Cancer Risk.

OBJECTIVE: Many models exist to estimate a woman's risk of development of breast cancer. At screening mammography, many imaging centers collect data required for these models to identify women who may benefit from supplemental screening and referral for cancer risk assessment. The purpose of this study was to discern perceptions and preferences of screening mammography patients regarding communication of estimated breast cancer risk. SUBJECTS AND METHODS: An anonymous survey was distributed to screening and surveillance mammography patients between April and June 2015. Survey questions were designed to assess patient preferences regarding the receipt and complexity of risk estimate communication, including hypothetical scenarios with and without > 20% estimated risk of breast cancer. The McNemar test and the Wilcoxon signed rank test were used with p ≤ 0.05 considered statistically significant. RESULTS: The survey was distributed to 1061 screening and surveillance mammography patients, and 503 patients responded (response rate, 47%). Although 86% (431/503) of patients expressed interest in learning their estimated risk, only 8% (38/503) had undergone formal risk assessment. The preferred method (241 respondents [26%]) of communication of risk < 20% was a mailed letter accompanying annual mammogram results. For risk > 20%, patients preferred oral communication and were 10-fold as likely to choose only oral communication (p < 0.000001). For risk < 20% and > 20%, patients preferred to learn their estimated risk in great detail (69% and 85%), although women were significantly more likely to choose greater detail for risk > 20% (p < 0.00001). CONCLUSION: Screening mammography patients expressed interest in learning their estimated risk of breast cancer regardless of their level of hypothetical risk.

Inflammatory breast cancer in accessory abdominal breast tissue.

Accessory breast tissue results from failure of the embryologic mammary ridge, also known as the milk line, to involute. As a result, ectopic breast tissue can develop anywhere along this ridge, which extends from the axilla-the most common location-to the groin. Primary breast cancer in accessory breast tissue is uncommon but has been reported in multiple prior studies. We present a rare case of inflammatory breast cancer presenting in upper abdominal accessory breast tissue in women with a personal history of ipsilateral breast cancer, and highlight the challenges of both diagnosis and treatment of breast cancer in accessory breast tissue.

Complement factor H autoantibodies are associated with early stage NSCLC.

PURPOSE: To discover diagnostic biomarkers associated with early-stage non-small cell lung cancer (NSCLC), we searched for autoantibodies preferentially present in stage I patients compared with patients with advanced-stage disease. Here we describe an autoantibody against complement factor H (CFH) and this autoantibody's association with early-stage NSCLC. EXPERIMENTAL DESIGN: Immunoblots were used to detect autoantibodies in the sera of stage I NSCLC patients. An autoantibody recognizing a 150 kDa protein was discovered, and the protein was identified by mass spectrometry. The association of the autoantibody with early-stage disease was suggested by the results of immunoblot analysis with sera from 28 stage I patients and 28 stage III/IV patients. This association was confirmed by protein microarray of sera from 125 NSCLC patients of all stages as well as 125 controls matched by age, gender, and smoking history. RESULTS: The immunoreactive protein was identified as CFH. By immunoblot analysis, anti-CFH autoantibody was found in 50% of stage I NSCLC patients and 11% of late-stage NSCLC patients (P = 0.003). By protein microarray analysis, patients with stage I NSCLC had a significantly higher incidence of anti-CFH antibody than those with late-stage NSCLC (P = 0.0051). The percentage of sera with a positive level of CFH autoantibody was 30.4% in stage I, 21.1% in stage II, 12.5% in stage III, 7.4% in stage IV, and 8.0% in the control group. CONCLUSIONS: These findings suggest that in patients with NSCLC, CFH autoantibody is a molecular marker associated with early-stage disease.

A genomic approach to identify regulatory nodes in the transcriptional network of systemic acquired resistance in plants.

Many biological processes are controlled by intricate networks of transcriptional regulators. With the development of microarray technology, transcriptional changes can be examined at the whole-genome level. However, such analysis often lacks information on the hierarchical relationship between components of a given system. Systemic acquired resistance (SAR) is an inducible plant defense response involving a cascade of transcriptional events induced by salicylic acid through the transcription cofactor NPR1. To identify additional regulatory nodes in the SAR network, we performed microarray analysis on Arabidopsis plants expressing the NPR1-GR (glucocorticoid receptor) fusion protein. Since nuclear translocation of NPR1-GR requires dexamethasone, we were able to control NPR1-dependent transcription and identify direct transcriptional targets of NPR1. We show that NPR1 directly upregulates the expression of eight WRKY transcription factor genes. This large family of 74 transcription factors has been implicated in various defense responses, but no specific WRKY factor has been placed in the SAR network. Identification of NPR1-regulated WRKY factors allowed us to perform in-depth genetic analysis on a small number of WRKY factors and test well-defined phenotypes of single and double mutants associated with NPR1. Among these WRKY factors we found both positive and negative regulators of SAR. This genomics-directed approach unambiguously positioned five WRKY factors in the complex transcriptional regulatory network of SAR. Our work not only discovered new transcription regulatory components in the signaling network of SAR but also demonstrated that functional studies of large gene families have to take into consideration sequence similarity as well as the expression patterns of the candidates.