Identification of metabolic pathways contributing to ER+ breast cancer disparities using a machine-learning pipeline.

African American (AA) women in the United States have a 40% higher breast cancer mortality rate than Non-Hispanic White (NHW) women. The survival disparity is particularly striking among (estrogen receptor positive) ER+ breast cancer cases. The purpose of this study is to examine whether there are racial differences in metabolic pathways typically activated in patients with ER+ breast cancer. We collected pretreatment plasma from AA and NHW ER+ breast cancer cases (AA n = 48, NHW n = 54) and cancer-free controls (AA n = 100, NHW n = 48) to conduct an untargeted metabolomics analysis using gas chromatography mass spectrometry (GC-MS) to identify metabolites that may be altered in the different racial groups. Unpaired t-test combined with multiple feature selection and prediction models were employed to identify race-specific altered metabolic signatures. This was followed by the identification of altered metabolic pathways with a focus in AA patients with breast cancer. The clinical relevance of the identified pathways was further examined in PanCancer Atlas breast cancer data set from The Cancer Genome Atlas Program (TCGA). We identified differential metabolic signatures between NHW and AA patients. In AA patients, we observed decreased circulating levels of amino acids compared to healthy controls, while fatty acids were significantly higher in NHW patients. By mapping these metabolites to potential epigenetic regulatory mechanisms, this study identified significant associations with regulators of metabolism such as methionine adenosyltransferase 1A (MAT1A), DNA Methyltransferases and Histone methyltransferases for AA individuals, and Fatty acid Synthase (FASN) and Monoacylglycerol lipase (MGL) for NHW individuals. Specific gene Negative Elongation Factor Complex E (NELFE) with histone methyltransferase activity, was associated with poor survival exclusively for AA individuals. We employed a comprehensive and novel approach that integrates multiple machine learning and statistical methods, coupled with human functional pathway analyses. The metabolic profile of plasma samples identified may help elucidate underlying molecular drivers of disproportionately aggressive ER+ tumor biology in AA women. It may ultimately lead to the identification of novel therapeutic targets. To our knowledge, this is a novel finding that describes a link between metabolic alterations and epigenetic regulation in AA breast cancer and underscores the need for detailed investigations into the biological underpinnings of breast cancer health disparities.

Pathologic Outcomes in Single Versus Multiple Areas of Architectural Distortion on Digital Breast Tomosynthesis.

BACKGROUND. Digital breast tomosynthesis (DBT) has led to increased detection of architectural distortion (AD). Management of patients with multiple areas of AD is not established. OBJECTIVE. The purpose of this article is to compare pathologic outcomes between single and multiple areas of AD identified on DBT. METHODS. This retrospective study included 402 patients (mean age, 56 years) who underwent image-guided core needle biopsy of AD visualized on DBT between April 7, 2017, and April 16, 2019. Patients were classified as having a single or multiple areas of AD according to the presence of distinct areas of AD described in the clinical radiology reports. The pathologic diagnosis for each AD was on the basis of the most aggressive pathology identified on either biopsy or surgical excision, if performed. Patients with single and multiple areas of AD were compared. RESULTS. The sample included 372 patients with a single AD (145 benign, 121 high risk, 105 malignant, one other) and 30 patients with multiple visualized ADs, including 66 biopsied ADs (10 benign, 35 high risk, 21 malignant). At pathologic assessment on a per-lesion basis, multiple compared with single ADs showed higher frequency of high-risk pathology (53.0% vs 32.5%, p = .002) but no difference in frequency of malignancy (31.8% vs 28.2%, p = .56). In multivariable analysis of a range of patient-related characteristics, the presence of single versus multiple areas of AD was not independently associated with malignancy (p = .51). In patients with multiple areas of AD, the most aggressive pathology (benign, high risk, or malignant) across all ADs was not associated with the number of ADs (p = .73). In 8 of 24 patients with at least two ipsilateral biopsied ADs, the ipsilateral areas varied in terms of most aggressive pathology; in 5 of 10 patients with contralateral biopsied ADs, the contralateral areas varied in most aggressive pathology. CONCLUSION. The presence of multiple areas of AD, compared with a single AD, was significantly more likely to yield high-risk pathology but was not significantly different in yield of malignancy. In patients with multiple ADs, multiple ipsilateral or contralateral ADs commonly varied in pathologic classification (benign, high risk, or malignant). CLINICAL IMPACT. These findings may help guide management of AD visualized by DBT, including multiple ADs. For patients with multiple areas of AD, biopsy of all areas may be warranted given variation in pathologic diagnoses.

Impact of the COVID-19 Pandemic on Breast Imaging: An Analysis of the National Mammography Database.

PURPOSE: The aim of this study was to quantify the initial decline and subsequent rebound in breast cancer screening metrics throughout the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Screening and diagnostic mammographic examinations, biopsies performed, and cancer diagnoses were extracted from the ACR National Mammography Database from March 1, 2019, through May 31, 2021. Patient (race and age) and facility (regional location, community type, and facility type) demographics were collected. Three time periods were used for analysis: pre-COVID-19 (March 1, 2019, to May 31, 2019), peak COVID-19 (March 1, 2020, to May 31, 2020), and COVID-19 recovery (March 1, 2021, to May 31, 2021). Analysis was performed at the facility level and overall between time periods. RESULTS: In total, 5,633,783 screening mammographic studies, 1,282,374 diagnostic mammographic studies, 231,390 biopsies, and 69,657 cancer diagnoses were analyzed. All peak COVID-19 metrics were less than pre-COVID-19 volumes: 36.3% of pre-COVID-19 for screening mammography, 57.9% for diagnostic mammography, 47.3% for biopsies, and 48.7% for cancer diagnoses. There was some rebound during COVID-19 recovery as a percentage of pre-COVID-19 volumes: 85.3% of pre-COVID-19 for screening mammography, 97.8% for diagnostic mammography, 91.5% for biopsies, and 92.0% for cancer diagnoses. Across various metrics, there was a disproportionate negative impact on older women, Asian women, facilities in the Northeast, and facilities affiliated with academic medical centers. CONCLUSIONS: COVID-19 had the greatest impact on screening mammography volumes, which have not returned to pre-COVID-19 levels. Cancer diagnoses declined significantly in the acute phase and have not fully rebounded, emphasizing the need to increase outreach efforts directed at specific patient population and facility types.

Letter to the editor on article by Dinh et al. Is it ethical to incentivize mammography screening in Medicaid populations? - A policy review and conceptual analysis. By Stamatia Destounis, MD and Sarah Friedewald MD.

Letter to the Editor on article by Dinh et al- response to the authors comments on " Is it ethical to incentivize mammography screening in Medicaid populations? - A policy review and conceptual analysis".

Using the Medical Audit to Improve Practice Performance.

Feedback to physicians on their clinical performance is critical to continuous learning and maintenance of skills as well as maintaining patient safety. However, it is fraught with challenges around both implementation and acceptance. Additionally, rewarding of performance improvement is not often done, putting into question the efficacy of the process. Physician audit and feedback have been studied extensively and shown to be beneficial in many fields of medicine. Documenting physician performance and sharing individual and group data have been positively linked to changing physician behavior, ultimately leading to improved patient outcomes. Although casual review of one's own performance is often the easiest approach, it is frequently over- or underestimated by self-evaluation. Objective measures are therefore important to provide concrete data on which physicians can act. A fundamental question remains in mammography: Is reporting the information to the physician and accreditation bodies enough, or should there be consequences for the radiologist and/or facility if there is outlier behavior?

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.

Screening Algorithms in Dense Breasts: AJR Expert Panel Narrative Review.

Screening mammography reduces breast cancer mortality; however, when used to examine women with dense breasts, its performance and resulting benefits are reduced. Increased breast density is an independent risk factor for breast cancer. Digital breast tomosynthesis (DBT), ultrasound (US), molecular breast imaging (MBI), MRI, and contrast-enhanced mammography (CEM) each have shown improved cancer detection in dense breasts when compared with 2D digital mammography (DM). DBT is the preferred mammographic technique for producing a simultaneous reduction in recalls (i.e., additional imaging). US further increases cancer detection after DM or DBT and reduces interval cancers (cancers detected in the interval between recommended screening examinations), but it also produces substantial additional false-positive findings. MBI improves cancer detection with an effective radiation dose that is approximately fourfold that of DM or DBT but is still within accepted limits. MRI provides the greatest increase in cancer detection and reduces interval cancers and late-stage disease; abbreviated techniques will reduce cost and improve availability. CEM appears to offer performance similar to that of MRI, but further validation is needed. Dense breast notification will soon be a national standard; therefore, understanding the performance of mammography and supplemental modalities is necessary to optimize screening for women with dense breasts.

False-Negative Rates of Breast Cancer Screening with and without Digital Breast Tomosynthesis.

Background Screening with digital breast tomosynthesis (DBT) improves breast cancer detection and recall rates compared with those obtained with digital mammography (DM); however, the impact of DBT on patient survival has not been established. False-negative (FN) screening examinations can be a surrogate for long-term outcomes, such as breast cancer morbidity and mortality. Purpose To determine if screening with DBT is associated with lower FN rates, detection of cancers with more favorable prognoses, and improved performance outcomes versus DM. Materials and Methods This retrospective study involved 10 academic and community practices. DM screening examinations 1 year prior to DBT implementation and DBT screening examinations from the start date until June 30, 2013, were linked to cancers through June 30, 2014, with data collection in 2016 and analysis in 2018-2019. Cancers after FN examinations were characterized by presentation, either symptomatic or asymptomatic. FN rates, sensitivity, specificity, cancer detection and recall rates, positive predictive values, tumor size, histologic features, and receptor profile were compared. Results A total of 380 641 screening examinations were included. There were 183 989 DBT and 196 652 DM examinations. With DBT, rates trended lower for overall FN examinations (DBT, 0.6 per 1000 screens; DM, 0.7 per 1000 screens; P = .20) and symptomatic FN examinations (DBT, 0.4 per 1000 screens; DM, 0.5 per 1000 screens; P = .21). Asymptomatic FN rates trended higher in women with dense breasts (DBT, 0.14 per 1000 screens; DM: 0.07 per 1000 screens; P = .07). With DBT, improved sensitivity (DBT, 89.8% [966 of 1076 cancers]; DM, 85.6% [789 of 922 cancers]; P = .004) and specificity (DBT, 90.7% [165 830 of 182 913 examinations]; DM, 89.1% [174 480 of 195 730 examinations]; P < .001) were observed. Overall, cancers identified with DBT were more frequently invasive (P < .001), had fewer positive lymph nodes (P = .04) and distant metastases (P = .01), and had lower odds of an FN finding of advanced cancer (odds ratio, 0.9 [95% CI: 0.5, 1.5]). Conclusion Screening with digital breast tomosynthesis improves sensitivity and specificity and reveals more invasive cancers with fewer nodal or distant metastases. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Schattner in this issue.

Breast Imaging Second Opinion Consultation: A Single Institution's Process of Improvement and Reform.

OBJECTIVE: To review a single institution's second opinion breast imaging process, data tracking, and metrics before and after implementing quality improvement changes and the effect on report turnaround time. METHODS: This Institutional Review Board approved retrospective quality improvement project was performed at a tertiary-care academic medical center and included patients 18 years or older who submitted their outside facility imaging for reinterpretation (any combination of mammography, breast ultrasonography, and/or magnetic resonance imaging performed within the last six months) with finalized second opinion reports between June 1, 2016, and July 17, 2017. Significant intradepartmental changes were implemented March 2017 with the goal to improve second opinion report turnaround time. Key metrics from 399 studies were analyzed before and after implemented changes. Two-sided Fisher's exact test was used to assess the significance of results. RESULTS: After department interventions, the percentage of outside reports available at the time of surgical consultation improved from 82% (213/259) to 91% (127/140), an 11% improvement (P < 0.05). The average number of days from initial second opinion consultation to the availability of final report improved from 10.2 days to 9 days, a 12% improvement. Prior to the changes, the number of days it took a radiologist to complete a report varied from 1 to 4 days, but afterwards was consistently 1 day or less. CONCLUSION: Implementation of second opinion intradepartmental changes demonstrated a significant improvement in report turnaround time and the number of finalized reports available at the time of surgical consultation. An efficient second opinion process is crucial to a breast imaging center, as it ultimately expedites patient surgical and oncological care.

Targeted Melanoma Screening: Risk Self-Assessment and Skin Self-Examination Education Delivered During Mammography of Women.

BACKGROUND: Melanoma, which is the sixth most common cancer in women, is visible on the surface of the skin; therefore, self-screening (skin self-examination [SSE]) may be beneficial. METHODS: A convenience sample of women undergoing mammography was sequentially assigned by week into this two-arm targeted melanoma screening intervention. Both groups saw an informational poster and received a brochure promoting risk self-identification and SSE education. One group received an additional 1-week SSE reminder. Participants completed baseline and 1- and 3-month follow-up surveys assessing SSE performance, identifying a concerning mole, scheduling a dermatology appointment, and anxiety due to the program. Performance of SSE between groups was compared using χ2 analysis. The electronic medical record was reviewed for diagnosis of concerning moles. RESULTS: At 1 month, 384 of 420 (91.4% retention) women completed the survey. Of those, 311 (80.9%) performed SSE. Of those who performed SSE, 54 (14%) found a concerning mole at either 1 or 3 months. At 3 months, 346 (82.4% retention) women completed the survey. The number of women who performed SSE did not differ between groups at 1 month (χ2 = 1.64, P = .17) or 3 months (χ2 = 1.58, P = .12). Seven melanomas were found among 34 women who identified a concerning mole; examination of 4.8 women yielded one melanoma. Anxiety was low with a median score of 9.5 (range = 0-42.9). CONCLUSIONS: Introducing melanoma risks and SSE education during mammography was feasible and did not demonstrate harms; thus, there is an opportunity to reach a large, at-risk population with limited burden for the participant and clinics.

Digital Breast Tomosynthesis: Clinical Operations.

Digital breast tomosynthesis (DBT) is rapidly becoming the standard of care for breast cancer screening. Implementing DBT into practice is relatively straightforward. However, there are important elements of the transition that one must consider to facilitate this process. Understanding the Digital Imaging and Communications in Medicine (DICOM) standard for DBT, as well as how images are displayed, is critical to a successful transition. Standardization of these processes will allow easier transmission of images from facility to facility, and limit the potential for errors in interpretation. Additionally, recent changes in federal regulations will require compliance with mandated training for the radiologist, technologist, and physicist, as well as accreditation for each DBT unit. These regulations aim to ensure high-quality imaging across the country as has been previously seen with standard digital mammography. Synthesized imaging is the most recent improvement for DBT, potentially obviating the need for a simultaneous traditional digital mammogram exposure. Studies have demonstrated near equivalent performance when comparing the combination imaging of DBT and digital mammography versus DBT combined with synthetic imaging. As the quality of the synthetic images continues to improve, it is increasingly likely that it will replace the traditional mammogram. Adherence to DBT-specific parameters will enhance the physician experience and ultimately translate to increased cancer detection and fewer false positive examinations, benefiting all women who are screened for breast cancer.

Lesion Localization Using Digital Breast Tomosynthesis: Where Did I Go Wrong?

The scroll bar on digital breast tomosynthesis has become an imperative tool that breast imaging radiologists rely on for help in identify lesions on the orthogonal view, targeting breast ultrasound, and performing challenging biopsies for one-view findings. The ability to predict the lesion location using the scroll bar not only saves time in the diagnostic setting but also reduces screening recalls when a finding can be confirmed as dermal. It is important, however, to recognize settings in which the location prediction can be misleading, such as for lesions in thin breast tissue or the anterior portion of the breast or if the breast is not appropriately positioned. In these situations, radiologists can use other diagnostic tools for problem solving.

Breast Cancer Screening: The Debate that Never Ends.

Screening mammography has been shown to decrease breast cancer deaths through randomized controlled trials. However, there remains significant debate surrounding the most appropriate time to commence screening and the optimal screening interval. Several national organizations have recently updated their guidelines by reanalyzing the published data. Interestingly, each organization has come to different conclusions regarding their recommendation for breast cancer screening in the average risk woman. Three of the main organizations that issue guidelines for breast cancer screening in the United States are reviewd in this chapter.

Lesion localization using the scroll bar on tomosynthesis: Why doesn't it always work?

The scroll bar on digital breast tomosynthesis (DBT) is an important tool that facilitates localization of lesions on the orthogonal view. While this works well most of the time, occasionally the location of the lesion as directed by the scroll bar is seemingly inaccurate. There are five important reasons why the scroll bar indicator may suggest a contradictory lesion location. Understanding specific scenarios when this may occur will aid the reader in reconciling these differences.