Low-dose acetylsalicylic acid reduces local inflammation and tissue perfusion in dense breast tissue in postmenopausal women.

PURPOSE: One major risk factor for breast cancer is high mammographic density. It has been estimated that dense breast tissue contributes to ~ 30% of all breast cancer. Prevention targeting dense breast tissue has the potential to improve breast cancer mortality and morbidity. Anti-estrogens, which may be associated with severe side-effects, can be used for prevention of breast cancer in women with high risk of the disease per se. However, no preventive therapy targeting dense breasts is currently available. Inflammation is a hallmark of cancer. Although the biological mechanisms involved in the increased risk of cancer in dense breasts is not yet fully understood, high mammographic density has been associated with increased inflammation. We investigated whether low-dose acetylsalicylic acid (ASA) affects local breast tissue inflammation and/or structural and dynamic changes in dense breasts. METHODS: Postmenopausal women with mammographic dense breasts on their regular mammography screen were identified. A total of 53 women were randomized to receive ASA 160 mg/day or no treatment for 6 months. Magnetic resonance imaging (MRI) was performed before and after 6 months for a sophisticated and continuous measure breast density by calculating lean tissue fraction (LTF). Additionally, dynamic quantifications including tissue perfusion were performed. Microdialysis for sampling of proteins in vivo from breasts and abdominal subcutaneous fat, as a measure of systemic effects, before and after 6 months were performed. A panel of 92 inflammatory proteins were quantified in the microdialysates using proximity extension assay. RESULTS: After correction for false discovery rate, 20 of the 92 inflammatory proteins were significantly decreased in breast tissue after ASA treatment, whereas no systemic effects were detected. In the no-treatment group, protein levels were unaffected. Breast density, measured by LTF on MRI, were unaffected in both groups. ASA significantly decreased the perfusion rate. The perfusion rate correlated positively with local breast tissue concentration of VEGF. CONCLUSIONS: ASA may shape the local breast tissue microenvironment into an anti-tumorigenic state. Trials investigating the effects of low-dose ASA and risk of primary breast cancer among postmenopausal women with maintained high mammographic density are warranted. Trial registration EudraCT: 2017-000317-22.

Screening mammography performance according to breast density: a comparison between radiologists versus standalone intelligence detection.

BACKGROUND: Artificial intelligence (AI) algorithms for the independent assessment of screening mammograms have not been well established in a large screening cohort of Asian women. We compared the performance of screening digital mammography considering breast density, between radiologists and AI standalone detection among Korean women. METHODS: We retrospectively included 89,855 Korean women who underwent their initial screening digital mammography from 2009 to 2020. Breast cancer within 12 months of the screening mammography was the reference standard, according to the National Cancer Registry. Lunit software was used to determine the probability of malignancy scores, with a cutoff of 10% for breast cancer detection. The AI's performance was compared with that of the final Breast Imaging Reporting and Data System category, as recorded by breast radiologists. Breast density was classified into four categories (A-D) based on the radiologist and AI-based assessments. The performance metrics (cancer detection rate [CDR], sensitivity, specificity, positive predictive value [PPV], recall rate, and area under the receiver operating characteristic curve [AUC]) were compared across breast density categories. RESULTS: Mean participant age was 43.5 ± 8.7 years; 143 breast cancer cases were identified within 12 months. The CDRs (1.1/1000 examination) and sensitivity values showed no significant differences between radiologist and AI-based results (69.9% [95% confidence interval [CI], 61.7-77.3] vs. 67.1% [95% CI, 58.8-74.8]). However, the AI algorithm showed better specificity (93.0% [95% CI, 92.9-93.2] vs. 77.6% [95% CI, 61.7-77.9]), PPV (1.5% [95% CI, 1.2-1.9] vs. 0.5% [95% CI, 0.4-0.6]), recall rate (7.1% [95% CI, 6.9-7.2] vs. 22.5% [95% CI, 22.2-22.7]), and AUC values (0.8 [95% CI, 0.76-0.84] vs. 0.74 [95% CI, 0.7-0.78]) (all P < 0.05). Radiologist and AI-based results showed the best performance in the non-dense category; the CDR and sensitivity were higher for radiologists in the heterogeneously dense category (P = 0.059). However, the specificity, PPV, and recall rate consistently favored AI-based results across all categories, including the extremely dense category. CONCLUSIONS: AI-based software showed slightly lower sensitivity, although the difference was not statistically significant. However, it outperformed radiologists in recall rate, specificity, PPV, and AUC, with disparities most prominent in extremely dense breast tissue.

Breast cancer patients enrolled in the Swiss mammography screening program "donna" demonstrate prolonged survival.

STUDY GOAL: We compared the survival rates of women with breast cancer (BC) detected within versus outside the mammography screening program (MSP) "donna". METHODS: We merged data from the MSP with the data from corresponding cancer registries to categorize BC cases as within MSP (screen-detected and interval carcinomas) and outside the MSP. We analyzed the tumor stage distribution, tumor characteristics and the survival of the women. We further estimated hazard ratios using Cox-regressions to account for different characteristics between groups and corrected the survival rates for lead-time bias. RESULTS: We identified 1057 invasive (ICD-10: C50) and in-situ (D05) BC cases within the MSP and 1501 outside the MSP between 2010 and 2019 in the Swiss cantons of St. Gallen and Grisons. BC within the MSP had a higher share of stage I carcinoma (46.5% vs. 33.0%; p < 0.01), a smaller (mean) tumor size (19.1 mm vs. 24.9 mm, p < 0.01), and fewer recurrences and metastases in the follow-up period (6.7% vs. 15.6%, p < 0.01). The 10-year survival rates were 91.4% for women within and 72.1% for women outside the MSP (p < 0.05). Survival difference persisted but decreased when women within the same tumor stage were compared. Lead-time corrected hazard ratios for the MSP accounted for age, tumor size and Ki-67 proliferation index were 0.550 (95% CI 0.389, 0.778; p < 0.01) for overall survival and 0.469 (95% CI 0.294, 0.749; p < 0.01) for BC related survival. CONCLUSION: Women participating in the "donna" MSP had a significantly higher overall and BC related survival rate than women outside the program. Detection of BC at an earlier tumor stage only partially explains the observed differences.

Breast screening participation and degree of spread of invasive breast cancer at diagnosis in mental health service users: A population linkage study.

BACKGROUND: Women living with mental health conditions may not have shared in improvements in breast cancer screening and care. No studies have directly examined the link between reduced screening participation and breast cancer spread in women using mental health (MH) services. METHODS: Population-wide linkage of a population cancer register, BreastScreen register, and mental health service data set in women aged 50 to 74 years in New South Wales, Australia, from 2008 to 2017. Incident invasive breast cancers were identified. Predictors of degree of spread (local, regional, metastatic) at diagnosis were examined using partial proportional odds regression, adjusting for age, socioeconomic status, rurality, and patterns of screening participation. RESULTS: A total of 29 966 incident cancers were identified and included 686 (2.4%) in women with MH service before cancer diagnoses. More than half of MH service users had regional or metastatic spread at diagnosis (adjusted odds ratio, 1.63; 95% CI, 1.41-1.89). MH service users had lower screening participation; however, advanced cancer was more common even when adjusting for screening status (adjusted odds ratio, 1.53; 95% CI, 1.32-1.77). Advanced cancer was more common in women with severe or persistent MH conditions. CONCLUSIONS: Low screening participation rates explain only small part of the risk of more advanced breast cancer in women who use MH services. More study is needed to understand possible mechanisms contributing to more advanced breast cancer in women living with MH conditions. Health systems need strategies to ensure that women living with MH conditions enjoy population gains in breast cancer outcomes.

Reproductive risk factors for breast cancer and association with novel breast density measurements among Hispanic, Black, and White women.

PURPOSE: There are differences in the distributions of breast cancer incidence and risk factors by race and ethnicity. Given the strong association between breast density and breast cancer, it is of interest describe racial and ethnic variation in the determinants of breast density. METHODS: We characterized racial and ethnic variation in reproductive history and several measures of breast density for Hispanic (n = 286), non-Hispanic Black (n = 255), and non-Hispanic White (n = 1694) women imaged at a single hospital. We quantified associations between reproductive factors and percent volumetric density (PVD), dense volume (DV), non-dense volume (NDV), and a novel measure of pixel intensity variation (V) using multivariable-adjusted linear regression, and tested for statistical heterogeneity by race and ethnicity. RESULTS: Reproductive factors most strongly associated with breast density were age at menarche, parity, and oral contraceptive use. Variation by race and ethnicity was most evident for the associations between reproductive factors and NDV (minimum p-heterogeneity:0.008) and V (minimum p-heterogeneity:0.004) and least evident for PVD (minimum p-heterogeneity:0.042) and DV (minimum p-heterogeneity:0.041). CONCLUSION: Reproductive choices, particularly those related to childbearing and oral contraceptive use, may contribute to racial and ethnic variation in breast density.

Comparisons of assessment pathways after abnormal mammography screening in Denmark, Norway, and Spain.

PURPOSE: To ensure high-quality screening programmes and effective utilization of resources, it is important to monitor how cancer detection is affected by different strategies performed at recall assessment. This study aimed to describe procedures performed at recall assessment and compare and evaluate the performance of the assessment in Denmark, Norway, and Spain in terms of screen-detected cancer (SDC) and interval cancer (IC) rates. METHODS: We included women aged 50-69 years from Denmark, Norway, and Spain, who were recalled for assessment after screening mammography, and recorded all procedures performed during six months after diagnosis, and the timing of the procedures. Women were followed for two years and screen-detected and interval cancer, and sensitivity of recall was calculated and compared. RESULTS: In total, data from 24,645 Danish, 30,050 Norwegian, and 41,809 Spanish women were included in the study. Most of the women had some assessment within 2 months in all three countries. SDC rates were higher in Denmark (0.57) and Norway (0.60) compared to Spain (0.38), as were the IC rates, i.e. 0.25 and 0.18 vs. 0.12, respectively. The sensitivity of the diagnostic follow-up was somewhat higher in Denmark (98.3%) and Norway (98.2%), compared to Spain (95.4%), but when excluding non-invasive assessment pathways, the sensitivities were comparable. CONCLUSION: This comparison study showed variation in the assessment procedures used in the three countries as well as the SDC and IC rates and the sensitivity of recall.

Contrast-enhanced mammography for surveillance in women with a personal history of breast cancer.

PURPOSE: Women with a personal history of breast cancer have an increased risk of subsequent breast malignancy and may benefit from more sensitive surveillance than conventional mammography (MG). We previously reported outcomes for first surveillance episode using contrast-enhanced mammography (CEM), demonstrating higher sensitivity and comparable specificity to MG. We now report CEM performance for subsequent surveillance. METHODS: A retrospective study of 1,190 women in an Australian hospital setting undergoing annual surveillance following initial surveillance CEM between June 2016 and December 2022. Outcome measures were recall rate, cancer detection rate, contribution of contrast to recalls, false positive rate, interval cancer rate and characteristics of surveillance detected and interval cancers. RESULTS: 2,592 incident surveillance episodes were analysed, of which 93% involved contrast-based imaging. Of 116 (4.5%) recall episodes, 40/116 (34%) recalls were malignant (27 invasive; 13 ductal carcinoma in situ), totalling 15.4 cancers per 1000 surveillance episodes. 55/116 (47%) recalls were contrast-directed including 17/40 (43%) true positive recalls. Tumour features were similar for contrast-directed recalls and other diagnoses. 8/9 (89%) of contrast-directed invasive recalls were Grade 2-3, and 5/9 (56%) were triple negative breast cancers. There were two symptomatic interval cancers (0.8 per 1000 surveillance episodes, program sensitivity 96%). CONCLUSION: Routine use of CEM in surveillance of women with PHBC led to an increase in the detection of clinically significant malignant lesions, with a low interval cancer rate compared to previous published series. Compared to mammographic surveillance, contrast-enhanced mammography increases the sensitivity of surveillance programs for women with PHBC.

Screening mammographic performance by race and age in the National Mammography Database: 29,479,665 screening mammograms from 13,181,241 women.

PURPOSE: There are insufficient large-scale studies comparing the performance of screening mammography in women of different races. This study aims to compare the screening performance metrics across racial and age groups in the National Mammography Database (NMD). METHODS: All screening mammograms performed between January 1, 2008, and December 31, 2021, in women aged 30-100 years from 746 mammography facilities in 46 U.S. states in the NMD were included. Patients were stratified by 10-year age intervals and 5 racial groups (African American, American Indian, Asian, White, unknown). Incidence of risk factors (breast density, personal history, family history of breast cancer, age), and time since prior exams were compared. Five screening mammography metrics were calculated: recall rate (RR), cancer detection rate (CDR), positive predictive values for recalls (PPV1), biopsy recommended (PPV2) and biopsy performed (PPV3). RESULTS: 29,479,655 screening mammograms performed in 13,181,241 women between January 1, 2008, and December 31, 2021, from the NMD were analyzed. The overall mean performance metrics were RR 10.00% (95% CI 9.99-10.02), CDR 4.18/1000 (4.16-4.21), PPV1 4.18% (4.16-4.20), PPV2 25.84% (25.72-25.97), PPV3 25.78% (25.66-25.91). With advancing age, RR significantly decreases, while CDR, PPV1, PPV2, and PPV3 significantly increase. Incidence of personal/family history of breast cancer, breast density, age, prior mammogram availability, and time since prior mammogram were mostly similar across all races. Compared to White women, African American women had significantly higher RR, but lower CDR, PPV1, PPV2 and PPV3. CONCLUSIONS: Benefits of screening mammography increase with age, including for women age > 70 and across all races. Screening mammography is effective; with lower RR and higher CDR, PPV2, and PPV3 with advancing age. African American women have poorer outcomes from screening mammography (higher RR and lower CDR), compared to White and all women in the NMD. Racial disparity can be partly explained by higher rate of African American women lost to follow up.

Contrast-Enhanced Mammography (CEM) compared to Breast Magnetic Resonance (MRI) in the evaluation of breast lobular neoplasia.

PURPOSE: To compare the diagnostic performance (detection, assessment of correct disease extent and multifocality/centricity) of Contrast-Enhanced Mammography (CEM) Versus Breast Magnetic Resonance (MRI) in the study of lobular neoplasms. METHODS: We retrospectively selected all the patients who underwent surgery for a lobular breast neoplasm, either an in situ or an invasive tumor, and had undergone both breast CEM and MRI examinations during the pre-surgical planning. Wilcoxon Signed Rank test was performed to assess the differences between size measurements using the different methods and the post-surgical pathological measurements, considered the gold standard. The agreement in identifying multifocality/multicentricity among the different methods and the pathology was assessed using the Kappa statistics. RESULTS: We selected 19 patients, of which one presented a bilateral neoplasm. Then, the images of these 19 patients were analyzed, for a total of 52 malignant breast lesions. We found no significant differences between the post-surgical pathological size of the lesions and the calculated size with CEM and MRI (p-value of the difference respectively 0.71 and 0.47). In all 20 cases, neoplasm detection was possible both with CEM and MRI. CEM and MRI showed an excellent ability to identify multifocal and multicentric cases (K statistic equal to 0.93 for both the procedures), while K statistic was 0.11 and 0.59 for FFDM and US, respectively. CONCLUSION: The findings of this study suggest that CEM is a reliable imaging technique in the preoperative setting of patients with lobular neoplasm, with comparable results to breast MRI.

Long-term breast cancer incidence trends by mammography, obesity, and menopausal hormone therapy.

PURPOSE: Over the past half century, the annual age-adjusted breast cancer incidence in the USA has fluctuated, potentially influenced by changes in mammography screening, obesity, and menopausal hormone therapy. As the relative contributions of these factors on breast cancer incidence have not been resolved, we assembled reliable sources of year-to-year changes in mammography, obesity, and hormone therapy to graphically display their relationship to breast cancer incidence through 50 years. METHODS: Year-to-year trends were assembled: for mammography from the Center for Disease Control National Health Interviews; for hormone therapy from the Collaborative Group on Hormonal Factors in Breast Cancer report; for obesity from the NCD (Non-Communicable Diseases) Risk Factor Collaboration; and for breast cancer for US women 50-64 years of age from Surveillance, Epidemiology, and End Results (SEER) registry findings. RESULTS: Increases in age-adjusted breast cancer incidence trend from about 1982 to 2002 track both mammography and hormone therapy use but not obesity. However, the sudden decrease in breast cancer incidence in 2003, subsequently sustained at a lower incidence level, only tracks the parallel reduction in hormone therapy use. CONCLUSION: The sustained reduction in hormone therapy use from 2003 provides a plausible explanation for most of the lower breast cancer incidence seen in US postmenopausal women during the last two decades. The strong observational study obesity association with higher breast cancer risk is not reflected in breast cancer incidence trends.

Breast cancer outcomes based on method of detection in community-based breast cancer registry.

PURPOSE: The impact of opportunistic screening mammography in the United States is difficult to quantify, partially due to lack of inclusion regarding method of detection (MOD) in national registries. This study sought to determine the feasibility of MOD collection in a multicenter community registry and to compare outcomes and characteristics of breast cancer based on MOD. METHODS: We conducted a retrospective study of breast cancer patients from a multicenter tumor registry in Missouri from January 2004 - December 2018. Registry data were extracted by certified tumor registrars and included MOD, clinicopathologic information, and treatment. MOD was assigned as screen-detected or clinically detected. Data were analyzed at the patient level. Chi-squared tests were used for categorical variable comparison and Mann-Whitney-U test was used for numerical variable comparison. RESULTS: 5351 women (median age, 63 years; interquartile range, 53-73 years) were included. Screen-detected cancers were smaller than clinically detected cancers (median size 12 mm vs. 25 mm; P < .001) and more likely node-negative (81% vs. 54%; P < .001), lower grade (P < .001), and lower stage (P < .001). Screen-detected cancers were more likely treated with lumpectomy vs. mastectomy (73% vs. 41%; P < .001) and less likely to require chemotherapy (24% vs. 52%; P < .001). Overall survival for patients with invasive breast cancer was higher for screen-detected cancers (89% vs. 74%, P < .0001). CONCLUSION: MOD can be routinely collected and linked to breast cancer outcomes through tumor registries, with demonstration of significant differences in outcome and characteristics of breast cancers based on MOD. Routine inclusion of MOD in US tumor registries would help quantify the impact of opportunistic screening mammography in the US.

Unveiling the potential of breast MRI: a game changer for BI-RADS 4A microcalcifications.

PURPOSE: To assess the diagnostic performance of breast MRI for BI-RADS 4A microcalcifications on mammography and propose a potential clinical pathway to avoid unnecessary biopsies. METHODS: Bibliometrics analysis of breast MRI and BI-RADS 4 was provided. A retrospective analysis was conducted on 139 women and 142 cases of BI-RADS 4A microcalcifications on mammography from Fudan University Shanghai Cancer Center. The mammographic BI-RADS level and the MRI reports were compared with the final pathological diagnosis. RESULTS: Much attention has been given to breast MRI and BI-RADS 4 in the literature. However, studies on BI-RADS 4A are limited. Pathological results showed 117 cases (82.4%) were benign lesions, malignant cases of 25 (17.6%) in our study. The positive predictive values (PPV), specificity, sensitivity and negative predictive values (NPV) of MRI were 44.2% (23/52), 75.2% (88/117), 92.0% (23/25), and 97.8% (88/90), respectively. Therefore, 75.2% (88/117) of biopsies for benign lesions could potentially be avoided. There were 2.2% (2/90) malignant lesions missed. Logistic regression indicated that patients who are postmenopausal (HR = 2.655, p = 0.012), have a history of breast cancer (family history) (HR = 2.833, p = 0.029), and exhibit clustered microcalcifications (HR = 2.179, p = 0.046) are more likely to have a higher MRI BI-RADS level. CONCLUSIONS: Breast MRI has the potential to improve the diagnosis of BI-RADS 4A microcalcifications on mammography. We propose a potential clinical pathway that patients with BI-RADS 4A on mammography who are premenopausal, have no personal history of breast cancer (family history) or have non-clustered distribution of calcifications can undergo MRI to avoid unnecessary biopsies.

Identify risk factors affecting participation of Turkish women in mammography screening for breast cancer prevention.

PURPOSE: Cancer screening is a public health intervention aiming to reduce cancer-caused deaths. This study aims to determine the factors affecting the mammography screening time among women aged 40-69. METHODS: The micro dataset obtained from the Türkiye Health Survey conducted by the Turkish Statistical Institute (TurkStat) in 2019 and 2022 was used in the present study. Stereotype logistic regression was used to determine the variables affecting mammography screening and period for breast cancer prevention in women in Türkiye. RESULTS: Given the results achieved from the analysis, it was found that factors such as age, marital status, general health condition, comorbidity, receiving psychosocial support, high blood lipid levels, and performing breast self-examinations affected women's adherence to cancer screening programs. CONCLUSION: Since adherence to mammography increases with age, it is recommended to pay importance to education for women approaching the age of mammography screening. Educated individuals are expected to have access to multiple sources of information as to cancer and to access this information more easily. In order to gain more insight into the recommended preventive measures and outcomes related to cancer, it is suggested to review policies, which will increase the educational level of women, and provide privileges in the field of education.

False negative breast cancers on imaging and associated risk factors: a single institution six-year analysis.

PURPOSE: Mitigating false negative imaging studies remains an important issue given its association with worse morbidity and mortality in patients with breast cancer. We aimed to identify risk factors that predispose to false negative breast imaging exams. METHODS: In an IRB-approved, HIPAA compliant retrospective study, we identified all patients who were diagnosed with breast cancer within 365 days of a negative imaging study assessed as BI-RADS 1-3 between January 1, 2014 and January 31, 2020. A matched cohort based on mammographic breast density was created from randomly selected studies with BI-RADS 4-5 designation that yielded breast cancer at pathology within the same time frame. Patient and cancer characteristics, prior personal history of breast cancer and gene mutation status were collected from patient charts. Pearson chi-squared and Student's t-test on two independent groups with significance at < 0.05 was used for statistical analysis. RESULTS: We identified 155 false negative studies of 129 missed cancers and 128 breast density matched true positive cancers. False negative studies were screening mammograms in 57.42% (89/155), diagnostic mammograms in 29.68% (46/155), ultrasounds in 6.45% (10/155) and MRIs in 6.45% (10/155). Rates of personal (41.09% vs. 18.75%, p < 0.001) and family history of breast cancer (68.22% vs. 49.21%, p = 0.002) were higher in the false negative cohort and remained significant when asymptomatic MRI-detected cancers were removed. CONCLUSION: Our findings suggest that supplemental screening may be useful in breast cancer survivors.

Germline pathogenic variants associated with triple-negative breast cancer in US Hispanic and Guatemalan women using hospital and community-based recruitment strategies.

PURPOSE: Recruit and sequence breast cancer subjects in Guatemalan and US Hispanic populations. Identify optimum strategies to recruit Latin American and Hispanic women into genetic studies of breast cancer. METHODS: We used targeted gene sequencing to identify pathogenic variants in 19 familial breast cancer susceptibility genes in DNA from unselected Hispanic breast cancer cases in the US and Guatemala. Recruitment across the US was achieved through community-based strategies. In addition, we obtained patients receiving cancer treatment at major hospitals in Texas and Guatemala. RESULTS: We recruited 287 Hispanic US women, 38 (13%) from community-based and 249 (87%) from hospital-based strategies. In addition, we ascertained 801 Guatemalan women using hospital-based recruitment. In our experience, a hospital-based approach was more efficient than community-based recruitment. In this study, we sequenced 103 US and 137 Guatemalan women and found 11 and 10 pathogenic variants, respectively. The most frequently mutated genes were BRCA1, BRCA2, CHEK2, and ATM. In addition, an analysis of 287 US Hispanic patients with pathology reports showed a significantly higher percentage of triple-negative disease in patients with pathogenic variants (41% vs. 15%). Finally, an analysis of mammography usage in 801 Guatemalan patients found reduced screening in women with a lower socioeconomic status (p < 0.001). CONCLUSION: Guatemalan and US Hispanic women have rates of hereditary breast cancer pathogenic variants similar to other populations and are more likely to have early age at diagnosis, a family history, and a more aggressive disease. Patient recruitment was higher using hospital-based versus community enrollment. This data supports genetic testing in breast cancer patients to reduce breast cancer mortality in Hispanic women.

Isolating the effect of confounding from the observed survival benefit of screening participants - a methodological approach illustrated by data from the German mammography screening programme.

BACKGROUND: Mammography screening programmes (MSP) aim to reduce breast cancer mortality by shifting diagnoses to earlier stages. However, it is difficult to evaluate the effectiveness of current MSP because analyses can only rely on observational data, comparing women who participate in screening with women who do not. These comparisons are subject to several biases: one of the most important is self-selection into the MSP, which introduces confounding and is difficult to control for. Here, we propose an approach to quantify confounding based on breast cancer survival analyses using readily available routine data sources. METHODS: Using data from the Cancer Registry of North Rhine-Westphalia, Germany, we estimate the relative contribution of confounding to the observed survival benefit of participants of the German MSP. This is accomplished by comparing non-participants, participants with screen-detected and participants with interval breast cancers for the endpoints "death from breast cancer" and "death from all causes other than breast cancer" - the latter being assumed to be unrelated to any MSP effect. By using different contrasts, we eliminate the effects of stage shift, lead and length time bias. The association of breast cancer detection mode with survival is analysed using Cox models in 68,230 women, aged 50-69 years, with breast cancer diagnosed in 2006-2014 and followed up until 2018. RESULTS: The hazard of dying from breast cancer was lower in participants with screen-detected cancer than in non-participants (HR = 0.21, 95% CI: 0.20-0.22), but biased by lead and length time bias, and confounding. When comparing participants with interval cancers and non-participants, the survival advantage was considerably smaller (HR = 0.62, 95% CI: 0.58-0.66), due to the elimination of stage shift and lead time bias. Finally, considering only mortality from causes other than breast cancer in the latter comparison, length time bias was minimised, but a survival advantage was still present (HR = 0.63, 95% CI: 0.56-0.70), which we attribute to confounding. CONCLUSIONS: This study shows that, in addition to stage shift, lead and length time bias, confounding is an essential component when comparing the survival of MSP participants and non-participants. We further show that the confounding effect can be quantified without explicit knowledge of potential confounders by using a negative control outcome.

Pectoral muscle removal in mammogram images: A novel approach for improved accuracy and efficiency.

PURPOSE: Accurate pectoral muscle removal is critical in mammographic breast density estimation and many other computer-aided algorithms. We propose a novel approach to remove pectoral muscles form mediolateral oblique (MLO) view mammograms and compare accuracy and computational efficiency with existing method (Libra). METHODS: A pectoral muscle identification pipeline was developed. The image is first binarized to enhance contrast and then the Canny algorithm was applied for edge detection. Robust interpolation is used to smooth out the pectoral muscle region. Accuracy and computational speed of pectoral muscle identification was assessed using 951 women (1,902 MLO mammograms) from the Joanne Knight Breast Health Cohort at Washington University School of Medicine. RESULTS: Our proposed algorithm exhibits lower mean error of 12.22% in comparison to Libra's estimated error of 20.44%. This 40% gain in accuracy was statistically significant (p < 0.001). The computational time for the proposed algorithm is 5.4 times faster when compared to Libra (5.1 s for proposed vs. 27.7 s for Libra per mammogram). CONCLUSION: We present a novel approach for pectoral muscle removal in mammogram images that demonstrates significant improvement in accuracy and efficiency compared to existing method. Our findings have important implications for the development of computer-aided systems and other automated tools in this field.

Latent pathway-based Bayesian models to identify intervenable factors of racial disparities in breast cancer stage at diagnosis.

PURPOSE: We built Bayesian Network (BN) models to explain roles of different patient-specific factors affecting racial differences in breast cancer stage at diagnosis, and to identify healthcare related factors that can be intervened to reduce racial health disparities. METHODS: We studied women age 67-74 with initial diagnosis of breast cancer during 2006-2014 in the National Cancer Institute's SEER-Medicare dataset. Our models included four measured variables (tumor grade, hormone receptor status, screening utilization and biopsy delay) expressed through two latent pathways-a tumor biology path, and health-care access/utilization path. We used various Bayesian model assessment tools to evaluate these two latent pathways as well as each of the four measured variables in explaining racial disparities in stage-at-diagnosis. RESULTS: Among 3,010 Black non-Hispanic (NH) and 30,310 White NH breast cancer patients, respectively 70.2% vs 76.9% were initially diagnosed at local stage, 25.3% vs 20.3% with regional stage, and 4.56% vs 2.80% with distant stage-at-diagnosis. Overall, BN performed approximately 4.7 times better than Classification And Regression Tree (CART) (Breiman L, Friedman JH, Stone CJ, Olshen RA. Classification and regression trees. CRC press; 1984) in predicting stage-at-diagnosis. The utilization of screening mammography is the most prominent contributor to the accuracy of the BN model. Hormone receptor (HR) status and tumor grade are useful for explaining racial disparity in stage-at diagnosis, while log-delay in biopsy impeded good prediction. CONCLUSIONS: Mammography utilization had a significant effect on racial differences in breast cancer stage-at-diagnosis, while tumor biology factors had less impact. Biopsy delay also aided in predicting local and regional stages-at-diagnosis for Black NH women but not for white NH women.

Estimating uninsured and underinsured women eligible for Minnesota's Breast Cancer Screening Program.

Since its inception in 1991, the mission of the National Breast and Cervical Cancer Early Detection Program's (NBCCEDP) mission is to improve access to mammography. This program has demonstrated evidence showing that it has improved breast cancer screening rates for women who are uninsured and underinsured. However, the literature has shown that NBCCEDP screenings are decreasing, and only reach a portion of eligible women. Reliable estimates at the sub-county level are needed to identify and reach eligible women. Our work builds upon previous estimates by integrating uninsured and insurance status into spatially adaptive filters. We use spatially adaptive filters to create small area estimates of standardized incidence ratios describing the utilization rate of NBCCEDP services in Minnesota. We integrate the American Community Survey (2010-2014) insurance status data to account for the percentage that an individual is uninsured. We test five models that integrate insurance status by age, sex, and race/ethnicity. Our composite model, which adjusts for age, sex, and race/ethnicity insurance statuses, reduces 95% of the estimation error. We estimate that there approximately 49,913.7 women eligible to receive services for Minnesota. We also create small geography (i.e., county and sub-county) estimates for Minnesota. The integration of the insurance data improved our utilization estimate. The development of these methods will allow state programs to more efficiently use their resources and understand their reach.

Understanding mechanisms of racial disparities in breast cancer: an assessment of screening and regular care in the Carolina Breast Cancer Study.

PURPOSE: Screening history influences stage at detection, but regular preventive care may also influence breast tumor diagnostic characteristics. Few studies have evaluated healthcare utilization (both screening and primary care) in racially diverse screening-eligible populations. METHODS: This analysis included 2,058 women age 45-74 (49% Black) from the Carolina Breast Cancer Study, a population-based cohort of women diagnosed with invasive breast cancer between 2008 and 2013. Screening history (threshold 0.5 mammograms per year) and pre-diagnostic healthcare utilization (i.e. regular care, based on responses to "During the past ten years, who did you usually see when you were sick or needed advice about your health?") were assessed as binary exposures. The relationship between healthcare utilization and tumor characteristics were evaluated overall and race-stratified. RESULTS: Among those lacking screening, Black participants had larger tumors (5 + cm) (frequency 19.6% vs 11.5%, relative frequency difference (RFD) = 8.1%, 95% CI 2.8-13.5), but race differences were attenuated among screening-adherent participants (10.2% vs 7.0%, RFD = 3.2%, 0.2-6.2). Similar trends were observed for tumor stage and mode of detection (mammogram vs lump). Among all participants, those lacking both screening and regular care had larger tumors (21% vs 8%, RR = 2.51, 1.76-3.56) and advanced (3B +) stage (19% vs 6%, RR = 3.15, 2.15-4.63) compared to the referent category (screening-adherent and regular care). Under-use of regular care and screening was more prevalent in socioeconomically disadvantaged areas of North Carolina. CONCLUSIONS: Access to regular care is an important safeguard for earlier detection. Our data suggest that health equity interventions should prioritize both primary care and screening.