Performance of Supplemental US Screening in Women with Dense Breasts and Varying Breast Cancer Risk: Results from the Breast Cancer Surveillance Consortium.

Background It is unclear whether breast US screening outcomes for women with dense breasts vary with levels of breast cancer risk. Purpose To evaluate US screening outcomes for female patients with dense breasts and different estimated breast cancer risk levels. Materials and Methods This retrospective observational study used data from US screening examinations in female patients with heterogeneously or extremely dense breasts conducted from January 2014 to October 2020 at 24 radiology facilities within three Breast Cancer Surveillance Consortium (BCSC) registries. The primary outcomes were the cancer detection rate, false-positive biopsy recommendation rate, and positive predictive value of biopsies performed (PPV3). Risk classification of participants was performed using established BCSC risk prediction models of estimated 6-year advanced breast cancer risk and 5-year invasive breast cancer risk. Differences in high- versus low- or average-risk categories were assessed using a generalized linear model. Results In total, 34 791 US screening examinations from 26 489 female patients (mean age at screening, 53.9 years ± 9.0 [SD]) were included. The overall cancer detection rate per 1000 examinations was 2.0 (95% CI: 1.6, 2.4) and was higher in patients with high versus low or average risk of 6-year advanced breast cancer (5.5 [95% CI: 3.5, 8.6] vs 1.3 [95% CI: 1.0, 1.8], respectively; P = .003). The overall false-positive biopsy recommendation rate per 1000 examinations was 29.6 (95% CI: 22.6, 38.6) and was higher in patients with high versus low or average 6-year advanced breast cancer risk (37.0 [95% CI: 28.2, 48.4] vs 28.1 [95% CI: 20.9, 37.8], respectively; P = .04). The overall PPV3 was 6.9% (67 of 975; 95% CI: 5.3, 8.9) and was higher in patients with high versus low or average 6-year advanced cancer risk (15.0% [15 of 100; 95% CI: 9.9, 22.2] vs 4.9% [30 of 615; 95% CI: 3.3, 7.2]; P = .01). Similar patterns in outcomes were observed by 5-year invasive breast cancer risk. Conclusion The cancer detection rate and PPV3 of supplemental US screening increased with the estimated risk of advanced and invasive breast cancer. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Helbich and Kapetas in this issue.

Reduction in Breast Cancer Death With Adjuvant Chemotherapy Among US Women According to Race, Ethnicity, and the 21-Gene Recurrence Score.

BACKGROUND: We previously showed the 21-gene breast recurrence score (RS) has lower prognostic accuracy for non-Hispanic Black (NHB) compared with non-Hispanic White (NHW) women with estrogen receptor (ER)-positive/HER2-negative breast cancer. The purpose of this study was to determine the clinical validity of the RS for predicting chemotherapy benefit as recommended in the current NCCN Guidelines for Breast Cancer among women from diverse racial/ethnic groups. METHODS: Using the SEER Oncotype database, we estimated propensity score-weighted hazard ratios (HRs) and 95% confidence intervals for breast cancer death with chemotherapy for women with ER-positive/HER2-negative, AJCC stages I-II, axillary node-negative, invasive breast cancer according to race/ethnicity. RESULTS: We included 6,033 (8.2%) Asian/Pacific Islander (API), 5,697 (7.8%) NHB, 6,688 (9.1%) Hispanic, and 54,945 (74.9%) NHW women. Breast cancer death was reduced with chemotherapy for NHB (HR, 0.48, 95% CI, 0.28-0.81), Hispanic (HR, 0.48; 95% CI, 0.25-0.94), and NHW (HR, 0.80; 95% CI, 0.65-0.99) women with an RS of 26 to 100. There was a nonsignificant reduction for API women (HR, 0.59; 95% CI, 0.28-1.24). For women with an RS of 11 to 25, there was no reduction in death for any racial/ethnic group. Among women aged ≤50 years, the reduction in breast cancer death with chemotherapy differed according to race (NHB: HR, 0.37 [95% CI, 0.20-0.67]; NHW: HR, 0.56 [95% CI, 0.44-0.74]; Pinteraction for chemotherapy * race <.0499). An exploratory subgroup analysis found that young NHB women may benefit from chemotherapy at a lower RS cutoff than other women. CONCLUSIONS: The RS was clinically validated as a predictive biomarker for NHB, Hispanic, and NHW women with ER-positive, axillary node-negative breast cancer, but it may underestimate the benefit of chemotherapy for young NHB women. If this finding is confirmed, the RS cutoff for recommending adjuvant chemotherapy for young NHB women with ER-positive, axillary node-negative breast cancer may need to be lower than for other women.

Association between adverse childhood experiences and later-life allostatic load in UK Biobank female participants.

BACKGROUND: Adverse childhood experiences during key developmental periods have been shown to impact long-term health outcomes. Adverse childhood experiences may include psychological, physical, or sexual abuse; neglect; or socioeconomic factors. Adverse childhood experiences are linked with an increase in poor health behavior such as smoking and alcohol consumption, and may also influence epigenetic changes, inflammatory response, metabolic changes, and allostatic load. OBJECTIVE: We sought to explore associations between adverse childhood experiences and allostatic load in adult female participants in the UK Biobank. DESIGN: The UK Biobank is a multisite cohort study established to capture lifestyle, environment, exposure, health history, and genotype data on individuals in the United Kingdom. METHODS: Adverse childhood experiences were assessed from the Childhood Trauma Screener, which measures abuse and neglect across five items. Biological measures at enrollment were used to construct allostatic load, including measures of metabolic, inflammatory, and cardiovascular function. Females with a cancer diagnosis prior to enrollment were removed as it may influence allostatic load. Poisson regression models were used to assess the association between adverse childhood experiences and allostatic load, accounting for a priori confounders. RESULTS: A total of 33,466 females with complete data were analyzed, with a median age at enrollment of 54 (range = 40-70) years. Among the study sample, the mean allostatic load ranged from 1.85 in those who reported no adverse childhood experiences to 2.45 in those with all adverse childhood experiences reported. In multivariable analysis, there was a 4% increase in average allostatic load among females for every additional adverse childhood experience reported (incidence rate ratio = 1.04, 95% confidence interval = 1.03-1.05). Similar results were observed when assessing individual adverse childhood experience components. CONCLUSION: This analysis supports a growing body of evidence suggesting that increased exposure to early life abuse or neglect is associated with increased allostatic load in females.

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.

Prognostic Value of SGK1 and Bcl-2 in Invasive Breast Cancer.

It is crucial to understand molecular alterations in breast cancer and how they relate to clinicopathologic factors. We have previously shown that the glucocorticoid receptor (GCR) protein expression was reduced in invasive breast carcinoma compared to normal breast tissue. Glucocorticoids, signaling through the GCR, regulate several cellular processes via downstream targets such as serum/glucocorticoid-regulated kinase 1 (SGK1) and B-cell lymphoma 2 (Bcl-2). We measured the expression of SGK1 and Bcl-2, in respective breast cancer tissue arrays, from a multiracial cohort of breast cancer patients. Higher cytoplasmic SGK1 staining was stronger in breast cancer tissue compared to normal tissue, especially in hormone receptor-negative cases. Conversely, the expression of cytoplasmic Bcl-2 was reduced in breast cancer compared to normal tissue, especially in hormone receptor-negative cases. Bcl-2 staining was associated with the self-reported racial/ethnic category, an earlier clinical stage, a lower histological grade, and a higher survival rate. Bcl-2 expression was associated with longer survival in models adjusted for age and race (HR = 0.32, 95% CI: 0.15, 0.65), and Bcl-2 expression remained strongly positively associated with protection from breast cancer death, with additional adjustments for ER/PR status (HR = 0.41, 95% CI: 0.2, 0.85). SGK1 and Bcl-2 may play biological roles in breast cancer development and/or progression.

National Performance Benchmarks for Screening Digital Breast Tomosynthesis: Update from the Breast Cancer Surveillance Consortium.

Background It is important to establish screening mammography performance benchmarks for quality improvement efforts. Purpose To establish performance benchmarks for digital breast tomosynthesis (DBT) screening and evaluate performance trends over time in U.S. community practice. Materials and Methods In this retrospective study, DBT screening examinations were collected from five Breast Cancer Surveillance Consortium (BCSC) registries between 2011 and 2018. Performance measures included abnormal interpretation rate (AIR), cancer detection rate (CDR), sensitivity, specificity, and false-negative rate (FNR) and were calculated based on the American College of Radiology Breast Imaging Reporting and Data System, fifth edition, and compared with concurrent BCSC DM screening examinations, previously published BCSC and National Mammography Database benchmarks, and expert opinion acceptable performance ranges. Benchmarks were derived from the distribution of performance measures across radiologists (n = 84 or n = 73 depending on metric) and were presented as percentiles. Results A total of 896 101 women undergoing 2 301 766 screening examinations (458 175 DBT examinations [median age, 58 years; age range, 18-111 years] and 1 843 591 DM examinations [median age, 58 years; age range, 18-109 years]) were included in this study. DBT screening performance measures were as follows: AIR, 8.3% (95% CI: 7.5, 9.3); CDR per 1000 screens, 5.8 (95% CI: 5.4, 6.1); sensitivity, 87.4% (95% CI: 85.2, 89.4); specificity, 92.2% (95% CI: 91.3, 93.0); and FNR per 1000 screens, 0.8 (95% CI: 0.7, 1.0). When compared with BCSC DM screening examinations from the same time period and previously published BCSC and National Mammography Database performance benchmarks, all performance measures were higher for DBT except sensitivity and FNR, which were similar to concurrent and prior DM performance measures. The following proportions of radiologists achieved acceptable performance ranges with DBT: 97.6% for CDR, 91.8% for sensitivity, 75.0% for AIR, and 74.0% for specificity. Conclusion In U.S. community practice, large proportions of radiologists met acceptable performance ranges for screening performance metrics with DBT. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Lee and Moy in this issue.

The role of facility and patient mix factors on recovery of screening and diagnostic mammography volumes following the initial COVID-19 pandemic wave.

INTRODUCTION: The goal of this study was to understand the extent to which mammography facilities were able to recover monthly screening and diagnostic mammography volumes to their prepandemic levels and to determine what facility and patient mix factors were associated with recovery. METHOD: Facilities, located in and adjacent to Cook County, Illinois, were eligible. In all, 58 screening and 30 diagnostic mammogram facilities submitted mammogram volumes by month with a cross-listing of patient ZIP codes by screening volumes. Monthly screening and diagnostic volumes for the 6-month immediate postpandemic period (July-December 2020) and for the subsequent postpandemic period (January-June 2021) were compared with the same months in 2019. ZIP code distributions were used to define patient mix characteristics related to disadvantage. RESULTS: Compared with the prepandemic period, Breast Imaging Centers of Excellence conducted roughly 50 fewer monthly screening mammograms (95% CI: -91, -9) but 50 more diagnostic mammograms (95% CI: 24, 82) on average in the immediate postpandemic period. Facilities serving a predominantly Black population conducted roughly 50 fewer monthly screens (95% CI: -93, -13) without any increase in monthly diagnostics. CONCLUSION: Highly accredited (and typically higher volume) facilities appeared to actively triage diagnostics, whereas lower resource facilities appeared to struggle to recover to prepandemic volumes without triage to diagnostics. The pandemic disproportionally impacted minority populations already affected by differential access to and utilization of high-quality mammography. Potential explanations are discussed. Policies should be strengthened to facilitate triaging of services during times of stress to the healthcare system.

Association of Social Determinants and Tumor Biology With Racial Disparity in Survival From Early-Stage, Hormone-Dependent Breast Cancer.

Importance: Black women with hormone receptor-positive breast cancer experience the greatest racial disparity in survival of all breast cancer subtypes. The relative contributions of social determinants of health and tumor biology to this disparity are uncertain. Objective: To determine the proportion of the Black-White disparity in breast cancer survival from estrogen receptor (ER)-positive, axillary node-negative breast cancer that is associated with adverse social determinants and high-risk tumor biology. Design, Setting, and Participants: A retrospective mediation analysis of factors associated with the racial disparity in breast cancer death for cases diagnosed between 2004 and 2015 with follow-up through 2016 was carried out using the Surveillance, Epidemiology, and End Results (SEER) Oncotype registry. The study included women in the SEER-18 registry who were aged 18 years or older at diagnosis of a first primary invasive breast cancer tumor that was axillary node-negative and ER-positive, who were Black (Black), non-Hispanic White (White), and for whom the 21-gene breast recurrence score was available. Data analysis took place between March 4, 2021, and November 15, 2022. Exposures: Census tract socioeconomic disadvantage, insurance status, tumor characteristics including the recurrence score, and treatment variables. Main Outcomes and Measures: Death due to breast cancer. Results: The analysis with 60 137 women (mean [IQR] age 58.1 [50-66] years) included 5648 (9.4%) Black women and 54 489 (90.6%) White women. With a median (IQR) follow-up time of 56 (32-86) months, the age-adjusted hazard ratio (HR) for breast cancer death among Black compared with White women was 1.82 (95% CI, 1.51-2.20). Neighborhood disadvantage and insurance status together mediated 19% of the disparity (mediated HR, 1.62; 95% CI, 1.31-2.00; P < .001) and tumor biological characteristics mediated 20% (mediated HR, 1.56; 95% CI, 1.28-1.90; P < .001). A fully adjusted model that included all covariates accounted for 44% of the racial disparity (mediated HR, 1.38; 95% CI, 1.11-1.71; P < .001). Neighborhood disadvantage mediated 8% of the racial difference in the probability of a high-risk recurrence score (P = .02). Conclusions and Relevance: In this study, racial differences in social determinants of health and indicators of aggressive tumor biology including a genomic biomarker were equally associated with the survival disparity in early-stage, ER-positive breast cancer among US women. Future research should examine more comprehensive measures of socioecological disadvantage, molecular mechanisms underlying aggressive tumor biology among Black women, and the role of ancestry-related genetic variants.

Multilevel Factors Associated With Time to Biopsy After Abnormal Screening Mammography Results by Race and Ethnicity.

Importance: Diagnostic delays in breast cancer detection may be associated with later-stage disease and higher anxiety, but data on multilevel factors associated with diagnostic delay are limited. Objective: To evaluate individual-, neighborhood-, and health care-level factors associated with differences in time from abnormal screening to biopsy among racial and ethnic groups. Design, Setting, and Participants: This prospective cohort study used data from women aged 40 to 79 years who had abnormal results in screening mammograms conducted in 109 imaging facilities across 6 US states between 2009 and 2019. Data were analyzed from February 21 to November 4, 2021. Exposures: Individual-level factors included self-reported race and ethnicity, age, family history of breast cancer, breast density, previous breast biopsy, and time since last mammogram; neighborhood-level factors included geocoded education and income based on residential zip codes and rurality; and health care-level factors included mammogram modality, screening facility academic affiliation, and facility onsite biopsy service availability. Data were also assessed by examination year. Main Outcome and Measures: The main outcome was unadjusted and adjusted relative risk (RR) of no biopsy within 30, 60, and 90 days using sequential log-binomial regression models. A secondary outcome was unadjusted and adjusted median time to biopsy using accelerated failure time models. Results: A total of 45 186 women (median [IQR] age at screening, 56 [48-65] years) with 46 185 screening mammograms with abnormal results were included. Of screening mammograms with abnormal results recommended for biopsy, 15 969 (34.6%) were not resolved within 30 days, 7493 (16.2%) were not resolved within 60 days, and 5634 (12.2%) were not resolved within 90 days. Compared with White women, there was increased risk of no biopsy within 30 and 60 days for Asian (30 days: RR, 1.66; 95% CI, 1.31-2.10; 60 days: RR, 1.58; 95% CI, 1.15-2.18), Black (30 days: RR, 1.52; 95% CI, 1.30-1.78; 60 days: 1.39; 95% CI, 1.22-1.60), and Hispanic (30 days: RR, 1.50; 95% CI, 1.24-1.81; 60 days: 1.38; 95% CI, 1.11-1.71) women; however, the unadjusted risk of no biopsy within 90 days only persisted significantly for Black women (RR, 1.28; 95% CI, 1.11-1.47). Sequential adjustment for selected individual-, neighborhood-, and health care-level factors, exclusive of screening facility, did not substantially change the risk of no biopsy within 90 days for Black women (RR, 1.27; 95% CI, 1.12-1.44). After additionally adjusting for screening facility, the increased risk for Black women persisted but showed a modest decrease (RR, 1.20; 95% CI, 1.08-1.34). Conclusions and Relevance: In this cohort study involving a diverse cohort of US women recommended for biopsy after abnormal results on screening mammography, Black women were the most likely to experience delays to diagnostic resolution after adjusting for multilevel factors. These results suggest that adjustment for multilevel factors did not entirely account for differences in time to breast biopsy, but unmeasured factors, such as systemic racism and other health care system factors, may impact timely diagnosis.

Structural racism is a mediator of disparities in acute myeloid leukemia outcomes.

Non-Hispanic Black (NHB) and Hispanic patients with acute myeloid leukemia (AML) have higher mortality rates than non-Hispanic White (NHW) patients despite more favorable genetics and younger age. A discrete survival analysis was performed on 822 adult patients with AML from 6 urban cancer centers and revealed inferior survival among NHB (hazard ratio [HR] = 1.59; 95% confidence interval [CI]: 1.15, 2.22) and Hispanic (HR = 1.25; 95% CI: 0.88, 1.79) patients compared with NHW patients. A multilevel analysis of disparities was then conducted to investigate the contribution of neighborhood measures of structural racism on racial/ethnic differences in survival. Census tract disadvantage and affluence scores were individually calculated. Mediation analysis of hazard of leukemia death between groups was examined across 6 composite variables: structural racism (census tract disadvantage, affluence, and segregation), tumor biology (European Leukemia Network risk and secondary leukemia), health care access (insurance and clinical trial enrollment), comorbidities, treatment patterns (induction intensity and transplant utilization), and intensive care unit (ICU) admission during induction chemotherapy. Strikingly, census tract measures accounted for nearly all of the NHB-NHW and Hispanic-NHW disparity in leukemia death. Treatment patterns, including induction intensity and allogeneic transplant, and treatment complications, as assessed by ICU admission during induction chemotherapy, were additional mediators of survival disparities in AML. This is the first study to formally test mediators for observed disparities in AML survival and highlights the need to investigate the mechanisms by which structural racism interacts with known prognostic and treatment factors to influence leukemia outcomes.

Cumulative Advanced Breast Cancer Risk Prediction Model Developed in a Screening Mammography Population.

BACKGROUND: Estimating advanced breast cancer risk in women undergoing annual or biennial mammography could identify women who may benefit from less or more intensive screening. We developed an actionable model to predict cumulative 6-year advanced cancer (prognostic pathologic stage II or higher) risk according to screening interval. METHODS: We included 931 186 women aged 40-74 years in the Breast Cancer Surveillance Consortium undergoing 2 542 382 annual (prior mammogram within 11-18 months) or 752 049 biennial (prior within 19-30 months) screening mammograms. The prediction model includes age, race and ethnicity, body mass index, breast density, family history of breast cancer, and prior breast biopsy subdivided by menopausal status and screening interval. We used fivefold cross-validation to internally validate model performance. We defined higher than 95th percentile as high risk (>0.658%), higher than 75th percentile to 95th or less percentile as intermediate risk (0.380%-0.658%), and 75th or less percentile as low to average risk (<0.380%). RESULTS: Obesity, high breast density, and proliferative disease with atypia were strongly associated with advanced cancer. The model is well calibrated and has an area under the receiver operating characteristics curve of 0.682 (95% confidence interval = 0.670 to 0.694). Based on women's predicted advanced cancer risk under annual and biennial screening, 69.1% had low or average risk regardless of screening interval, 12.4% intermediate risk with biennial screening and average risk with annual screening, and 17.4% intermediate or high risk regardless of screening interval. CONCLUSION: Most women have low or average advanced cancer risk and can undergo biennial screening. Intermediate-risk women may consider annual screening, and high-risk women may consider supplemental imaging in addition to annual screening.

Health Insurance Status as a Predictor of Mode of Colon Cancer Detection but Not Stage at Diagnosis: Implications for Early Detection.

OBJECTIVE: For colon cancer patients, one goal of health insurance is to improve access to screening that leads to early detection, early-stage diagnosis, and polyp removal, all of which results in easier treatment and better outcomes. We examined associations among health insurance status, mode of detection (screen detection vs symptomatic presentation), and stage at diagnosis (early vs late) in a diverse sample of patients recently diagnosed with colon cancer from the Chicago metropolitan area. METHODS: Data came from the Colon Cancer Patterns of Care in Chicago study of racial and socioeconomic disparities in colon cancer screening, diagnosis, and care. We collected data from the medical records of non-Hispanic Black and non-Hispanic White patients aged ≥50 and diagnosed with colon cancer from October 2010 through January 2014 (N = 348). We used logistic regression with marginal standardization to model associations between health insurance status and study outcomes. RESULTS: After adjusting for age, race, sex, and socioeconomic status, being continuously insured 5 years before diagnosis and through diagnosis was associated with a 20 (95% CI, 8-33) percentage-point increase in prevalence of screen detection. Screen detection in turn was associated with a 15 (95% CI, 3-27) percentage-point increase in early-stage diagnosis; however, nearly half (47%; n = 54) of the 114 screen-detected patients were still diagnosed at late stage (stage 3 or 4). Health insurance status was not associated with earlier stage at diagnosis. CONCLUSIONS: For health insurance to effectively shift stage at diagnosis, stronger associations are needed between health insurance and screening-related detection; between screening-related detection and early stage at diagnosis; or both. Findings also highlight the need to better understand factors contributing to late-stage colon cancer diagnosis despite screen detection.

Genetic Variation and Immunohistochemical Localization of the Glucocorticoid Receptor in Breast Cancer Cases from the Breast Cancer Care in Chicago Cohort.

BACKGROUND: Glucocorticoid, one of the primary mediators of stress, acts via its receptor, the glucocorticoid receptor (GCR/NR3C1), to regulate a myriad of physiological processes. We measured the genetic variation and protein expression of GCR, and the genes that regulate GCR function or response and examined whether these alterations were associated with breast cancer clinicopathological characteristics. METHOD: We used samples from a multiracial cohort of breast cancer patients to assess the association between breast cancer characteristics and the genetic variants of single nucleotide polymorphisms (SNPs) in GCR/NR3C1, FKBP5, Sgk1, IL-6, ADIPOQ, LEPR, SOD2, CAT, and BCL2. RESULTS: Several SNPs were associated with breast cancer characteristics, but statistical significance was lost after adjustment for multiple comparisons. GCR was detected in all normal breast tissues and was predominantly located in the nuclei of the myoepithelial cell layer, whereas the luminal layer was negative for GCR. GCR expression was significantly decreased in all breast cancer tissue types, compared to nontumor tissue, but was not associated with breast cancer characteristics. We found that high nuclear GCR expression was associated with basal cell marker cytokeratin 5/6 positivity. CONCLUSION: GCR expression is reduced in breast cancer tissue and correlates with the basal cell marker CK5/6.

Assessment of a Risk-Based Approach for Triaging Mammography Examinations During Periods of Reduced Capacity.

Importance: Breast cancer screening, surveillance, and diagnostic imaging services were profoundly limited during the initial phase of the coronavirus disease 2019 (COVID-19) pandemic. Objective: To develop a risk-based strategy for triaging mammograms during periods of decreased capacity. Design, Setting, and Participants: This population-based cohort study used data collected prospectively from mammography examinations performed in 2014 to 2019 at 92 radiology facilities in the Breast Cancer Surveillance Consortium. Participants included individuals undergoing mammography. Data were analyzed from August 10 to November 3, 2020. Exposures: Clinical indication for screening, breast symptoms, personal history of breast cancer, age, time since last mammogram/screening interval, family history of breast cancer, breast density, and history of high-risk breast lesion. Main Outcomes and Measures: Combinations of clinical indication, clinical history, and breast cancer risk factors that subdivided mammograms into risk groups according to their cancer detection rate were identified using classification and regression trees. Results: The cohort included 898 415 individuals contributing 1 878 924 mammograms (mean [SD] age at mammogram, 58.6 [11.2] years) interpreted by 448 radiologists, with 1 722 820 mammograms in individuals without a personal history of breast cancer and 156 104 mammograms in individuals with a history of breast cancer. Most individuals were aged 50 to 69 years at imaging (1 113 174 mammograms [59.2%]), and 204 305 (11.2%) were Black, 206 087 (11.3%) were Asian or Pacific Islander, 126 677 (7.0%) were Hispanic or Latina, and 40 021 (2.2%) were another race/ethnicity or mixed race/ethnicity. Cancer detection rates varied widely based on clinical indication, breast symptoms, personal history of breast cancer, and age. The 12% of mammograms with very high (89.6 [95% CI, 82.3-97.5] to 122.3 [95% CI, 108.1-138.0] cancers detected per 1000 mammograms) or high (36.1 [95% CI, 33.1-39.3] to 47.5 [95% CI, 42.4-53.3] cancers detected per 1000 mammograms) cancer detection rates accounted for 55% of all detected cancers and included mammograms to evaluate an abnormal mammogram or breast lump in individuals of all ages regardless of breast cancer history, to evaluate breast symptoms other than lump in individuals with a breast cancer history or without a history but aged 60 years or older, and for short-interval follow-up in individuals aged 60 years or older without a breast cancer history. The 44.2% of mammograms with very low cancer detection rates accounted for 13.1% of detected cancers and included annual screening mammograms in individuals aged 50 to 69 years (3.8 [95% CI, 3.5-4.1] cancers detected per 1000 mammograms) and all screening mammograms in individuals younger than 50 years regardless of screening interval (2.8 [95% CI, 2.6-3.1] cancers detected per 1000 mammograms). Conclusions and Relevance: In this population-based cohort study, clinical indication and individual risk factors were associated with cancer detection and may be useful for prioritizing mammography in times and settings of decreased capacity.

Comparative Access to and Use of Digital Breast Tomosynthesis Screening by Women's Race/Ethnicity and Socioeconomic Status.

Importance: Digital breast tomosynthesis (DBT) has reduced recall and increased cancer detection compared with digital mammography (DM), depending on women's age and breast density. Whether DBT screening access and use are equitable across groups of women based on race/ethnicity and socioeconomic characteristics is uncertain. Objective: To determine women's access to and use of DBT screening based on race/ethnicity, educational attainment, and income. Design, Setting, and Participants: This cross-sectional study included 92 geographically diverse imaging facilities across 5 US states, at which a total of 2 313 118 screening examinations were performed among women aged 40 to 89 years from January 1, 2011, to December 31, 2017. Data were analyzed from June 13, 2019, to August 18, 2020. Exposures: Women's race/ethnicity, educational level, and community-level household income. Main Outcomes and Measures: Access to DBT (on-site access) at time of screening by examination year and actual use of DBT vs DM screening by years since facility-level DBT adoption (≤5 years). Results: Among the 2 313 118 screening examinations included in the analysis, the proportion of women who had DBT access at the time of their screening appointment increased from 11 558 of 354 107 (3.3%) in 2011 to 194 842 of 235 972 (82.6%) in 2017. In 2012, compared with White women, Black (relative risk [RR], 0.05; 95% CI, 0.03-0.11), Asian American (RR, 0.28; 95% CI, 0.11-0.75), and Hispanic (RR, 0.38; 95% CI, 0.18-0.80) women had significantly less DBT access, and women with less than a high school education had lower DBT access compared with college graduates (RR, 0.18; 95% CI, 0.10-0.32). Among women attending facilities with both DM and DBT available at the time of screening, Black women experienced lower DBT use compared with White women attending the same facility (RRs, 0.83 [95% CI, 0.82-0.85] to 0.98 [95% CI, 0.97-0.99]); women with lower educational level experienced lower DBT use (RRs, 0.79 [95% CI, 0.74-0.84] to 0.88 [95% CI, 0.85-0.91] for non-high school graduates and 0.90 [95% CI, 0.89-0.92] to 0.96 [95% CI, 0.93-0.99] for high school graduates vs college graduates); and women within the lowest income quartile experienced lower DBT use vs women in the highest income quartile (RRs, 0.89 [95% CI, 0.87-0.91] to 0.99 [95% CI, 0.98-1.00]) regardless of the number of years after facility-level DBT adoption. Conclusions and Relevance: In this cross-sectional study, women of minority race/ethnicity and lower socioeconomic status experienced lower DBT access during the early adoption period and persistently lower DBT use when available over time. Future efforts should address racial/ethnic, educational, and financial barriers to DBT screening.

The "Sweet Spot" Revisited: Optimal Recall Rates for Cancer Detection With 2D and 3D Digital Screening Mammography in the Metro Chicago Breast Cancer Registry.

OBJECTIVE. One central question pertaining to mammography quality relates to discerning the optimal recall rate to maximize cancer detection while minimizing unnecessary downstream diagnostic imaging and breast biopsies. We examined the trade-offs for higher recall rates in terms of biopsy recommendations and cancer detection in a single large health care organization. MATERIALS AND METHODS. We included 2D analog, 2D digital, and 3D digital (tomosynthesis) screening mammography examinations among women 40-79 years old performed between January 1, 2005, and December 31, 2017, with cancer follow-up through 2018. There were 36, 67, and 38 radiologists who read at least 1000 2D analog examinations, 2D digital examinations, and 3D tomosynthesis examinations, respectively, who were included in these analyses. Using logistic regression with marginal standardization, we estimated radiologist-specific mean recall (abnormal interpretations/1000 mammograms), biopsy recommendation, cancer detection (screening-detected in situ and invasive cancers/1000 mammograms), and minimally invasive cancer detection rates while adjusting for differences in patient characteristics. RESULTS. Among 1,060,655 screening mammograms, the mean recall rate was 10.7%, the cancer detection rate was 4.0/1000 mammograms, and the biopsy recommendation rate was 1.60%. Recall rates between 7% and 9% appeared to maximize cancer detection while minimizing unnecessary biopsies. CONCLUSION. The results of this investigation are in contrast to those of a recent study suggesting appropriateness of higher recall rates. The "sweet spot" for optimal cancer detection appears to be in the recall rate range of 7-9% for both 2D digital mammography and 3D tomosynthesis. Too many women are being called back for diagnostic imaging, and new benchmarks could be set to reduce this burden.

Race and Gender Differences in Awareness of Colorectal Cancer Screening Tests and Guidelines Among Recently Diagnosed Colon Cancer Patients in an Urban Setting.

The purpose of this study was to first characterize the prevalence of recall, recognition, and knowledge of colon cancer screening tests and guidelines (collectively, "awareness") among non-Hispanic black (NHB) and NH white (NHW) urban colon cancer patients. Second, we sought to examine whether awareness was associated with mode of cancer detection. Low awareness regarding colon cancer screening tests and guidelines may explain low screening rates and high prevalence of symptomatic detection. We examined recall, recognition, and knowledge of colorectal cancer (CRC) screening tests and guidelines and their associations with mode of cancer detection (symptomatic versus screen-detected) in 374 newly diagnosed NHB and NHW patients aged 45-79. Patients were asked to name or describe any test to screen for colon cancer (recall); next, they were given descriptions of stool testing and colonoscopy and asked if they recognized each test (recognition). Lastly, patients were asked if they knew the screening guidelines (knowledge). Overall, awareness of CRC screening guidelines was low; just 20% and 13% of patients knew colonoscopy and fecal test guidelines, respectively. Awareness of CRC screening tests and guidelines was especially low among NHB males, socioeconomically disadvantaged individuals, and those diagnosed at public healthcare facilities. Inability to name or recall a single test was associated with reduced screen-detected cancer compared with recall of at least one test (36% vs. 22%, p = 0.01). Low awareness of CRC screening tests is a risk factor for symptomatic detection of colon cancer.

Family history of breast cancer in men with non-BRCA male breast cancer: implications for cancer risk counseling.

PURPOSE: The role of genetic predisposition in male breast cancer (MBC) patients who test negative for a BRCA mutation is unclear. The aim of this study is to define the association between MBC and family history of breast cancer in patients without mutations in BRCA1 or BRCA2. METHODS: We conducted an unmatched case-control study with men who received commercial testing for germline mutations in cancer susceptibility genes, including 3,647 MBC cases who tested negative for deleterious mutations in BRCA1/BRCA2, and 4,269 men with a personal history of colorectal cancer who tested negative for mutations in DNA mismatch repair genes to serve as controls. Associations between family history of breast cancer and MBC were estimated using unconditional multivariable logistic regression with adjustment for age, race/ethnicity and year of testing. RESULTS: Breast cancer in a first- or second-degree relative was associated with a four-fold increased odds of MBC (OR 4.7; 95% CI 4.1, 5.3). Associations with MBC were strongest for family history of breast cancer in 2 or more first-degree relatives (FDR) (OR 7.8; 95% CI 5.2, 11.6), for probands and FDR diagnosed at age < 45 years (OR 6.9; 95% CI 3.9, 12.4), and for family history of MBC (OR 17.9; 95% CI 7.6, 42.1). Findings were confirmed in a sensitivity analysis of MBC cases who tested negative on a 25-gene pan-cancer panel. CONCLUSIONS: MBC patients without mutations in BRCA1/2 have significantly higher odds of a family history of breast cancer, suggesting the existence of unidentified MBC susceptibility alleles.