Loss of PPARγ activity characterizes early protumorigenic stromal reprogramming and dictates the therapeutic window of opportunity.

Although robustly expressed in the disease-free (DF) breast stroma, CD36 is consistently absent from the stroma surrounding invasive breast cancers (IBCs). In this study, we primarily observed CD36 expression in adipocytes and intralobular capillaries within the DF breast. Larger vessels concentrated in interlobular regions lacked CD36 and were instead marked by the expression of CD31. When evaluated in perilesional capillaries surrounding ductal carcinoma in situ, a nonobligate IBC precursor, CD36 loss was more commonly observed in lesions associated with subsequent IBC. Peroxisome proliferator-activated receptor γ (PPARγ) governs the expression of CD36 and genes involved in differentiation, metabolism, angiogenesis, and inflammation. Coincident with CD36 loss, we observed a dramatic suppression of PPARγ and its target genes in capillary endothelial cells (ECs) and pericytes, which typically surround and support the stability of the capillary endothelium. Factors present in conditioned media from malignant cells repressed PPARγ and its target genes not only in cultured ECs and pericytes but also in adipocytes, which require PPARγ for proper differentiation. In addition, we identified a role for PPARγ in opposing the transition of pericytes toward a tumor-supportive myofibroblast phenotype. In mouse xenograft models, early intervention with rosiglitazone, a PPARγ agonist, demonstrated significant antitumor effects; however, following the development of a palpable tumor, the antitumor effects of rosiglitazone were negated by the repression of PPARγ in the mouse stroma. In summary, PPARγ activity in healthy tissues places several stromal cell types in an antitumorigenic state, directly inhibiting EC proliferation, maintaining adipocyte differentiation, and suppressing the transition of pericytes into tumor-supportive myofibroblasts.

Breast density knowledge and willingness to delay treatment for pre-operative breast cancer imaging among women with a personal history of breast cancer.

BACKGROUND: Following a breast cancer diagnosis, it is uncertain whether women's breast density knowledge influences their willingness to undergo pre-operative imaging to detect additional cancer in their breasts. We evaluated women's breast density knowledge and their willingness to delay treatment for pre-operative testing. METHODS: We surveyed women identified in the Breast Cancer Surveillance Consortium aged ≥ 18 years, with first breast cancer diagnosed within the prior 6-18 months, who had at least one breast density measurement within the 5 years prior to their diagnosis. We assessed women's breast density knowledge and correlates of willingness to delay treatment for 6 or more weeks for pre-operative imaging via logistic regression. RESULTS: Survey participation was 28.3% (969/3,430). Seventy-two percent (469/647) of women with dense and 11% (34/322) with non-dense breasts correctly knew their density (p < 0.001); 69% (665/969) of all women knew dense breasts make it harder to detect cancers on a mammogram; and 29% (285/969) were willing to delay treatment ≥ 6 weeks to undergo pre-operative imaging. Willingness to delay treatment did not differ by self-reported density (OR:0.99 for non-dense vs. dense; 95%CI: 0.50-1.96). Treatment with chemotherapy was associated with less willingness to delay treatment (OR:0.67; 95%CI: 0.46-0.96). Having previously delayed breast cancer treatment more than 3 months was associated with an increased willingness to delay treatment for pre-operative imaging (OR:2.18; 95%CI: 1.26-3.77). CONCLUSIONS: Understanding of personal breast density was not associated with willingness to delay treatment 6 or more weeks for pre-operative imaging, but aspects of a woman's treatment experience were. CLINICALTRIALS: GOV : NCT02980848 registered December 2, 2016.

Collaborative Modeling to Compare Different Breast Cancer Screening Strategies: A Decision Analysis for the US Preventive Services Task Force.

Importance: The effects of breast cancer incidence changes and advances in screening and treatment on outcomes of different screening strategies are not well known. Objective: To estimate outcomes of various mammography screening strategies. Design, Setting, and Population: Comparison of outcomes using 6 Cancer Intervention and Surveillance Modeling Network (CISNET) models and national data on breast cancer incidence, mammography performance, treatment effects, and other-cause mortality in US women without previous cancer diagnoses. Exposures: Thirty-six screening strategies with varying start ages (40, 45, 50 years) and stop ages (74, 79 years) with digital mammography or digital breast tomosynthesis (DBT) annually, biennially, or a combination of intervals. Strategies were evaluated for all women and for Black women, assuming 100% screening adherence and "real-world" treatment. Main Outcomes and Measures: Estimated lifetime benefits (breast cancer deaths averted, percent reduction in breast cancer mortality, life-years gained), harms (false-positive recalls, benign biopsies, overdiagnosis), and number of mammograms per 1000 women. Results: Biennial screening with DBT starting at age 40, 45, or 50 years until age 74 years averted a median of 8.2, 7.5, or 6.7 breast cancer deaths per 1000 women screened, respectively, vs no screening. Biennial DBT screening at age 40 to 74 years (vs no screening) was associated with a 30.0% breast cancer mortality reduction, 1376 false-positive recalls, and 14 overdiagnosed cases per 1000 women screened. Digital mammography screening benefits were similar to those for DBT but had more false-positive recalls. Annual screening increased benefits but resulted in more false-positive recalls and overdiagnosed cases. Benefit-to-harm ratios of continuing screening until age 79 years were similar or superior to stopping at age 74. In all strategies, women with higher-than-average breast cancer risk, higher breast density, and lower comorbidity level experienced greater screening benefits than other groups. Annual screening of Black women from age 40 to 49 years with biennial screening thereafter reduced breast cancer mortality disparities while maintaining similar benefit-to-harm trade-offs as for all women. Conclusions: This modeling analysis suggests that biennial mammography screening starting at age 40 years reduces breast cancer mortality and increases life-years gained per mammogram. More intensive screening for women with greater risk of breast cancer diagnosis or death can maintain similar benefit-to-harm trade-offs and reduce mortality disparities.

Variation in second breast cancer risk after primary invasive cancer by time since primary cancer diagnosis and estrogen receptor status.

BACKGROUND: In women with previously treated breast cancer, occurrence and timing of second breast cancers have implications for surveillance. The authors examined the timing of second breast cancers by primary cancer estrogen receptor (ER) status in the Breast Cancer Surveillance Consortium. METHODS: Women who were diagnosed with American Joint Commission on Cancer stage I-III breast cancer were identified within six Breast Cancer Surveillance Consortium registries from 2000 to 2017. Characteristics collected at primary breast cancer diagnosis included demographics, ER status, and treatment. Second breast cancer events included subsequent ipsilateral or contralateral breast cancers diagnosed >6 months after primary diagnosis. The authors examined cumulative incidence and second breast cancer rates by primary cancer ER status during 1-5 versus 6-10 years after diagnosis. RESULTS: At 10 years, the cumulative second breast cancer incidence was 11.8% (95% confidence interval [CI], 10.7%-13.1%) for women with ER-negative disease and 7.5% (95% CI, 7.0%-8.0%) for those with ER-positive disease. Women with ER-negative cancer had higher second breast cancer rates than those with ER-positive cancer during the first 5 years of follow-up (16.0 per 1000 person-years [PY]; 95% CI, 14.2-17.9 per 1000 PY; vs. 7.8 per 1000 PY; 95% CI, 7.3-8.4 per 1000 PY, respectively). After 5 years, second breast cancer rates were similar for women with ER-negative versus ER-positive breast cancer (12.1 per 1000 PY; 95% CI, 9.9-14.7; vs. 9.3 per 1000 PY; 95% CI, 8.4-10.3 per 1000 PY, respectively). CONCLUSIONS: ER-negative primary breast cancers are associated with a higher risk of second breast cancers than ER-positive cancers during the first 5 years after diagnosis. Further study is needed to examine the potential benefit of more intensive surveillance targeting these women in the early postdiagnosis period.

Breast cancer risk characteristics of women undergoing whole-breast ultrasound screening versus mammography alone.

BACKGROUND: There are no consensus guidelines for supplemental breast cancer screening with whole-breast ultrasound. However, criteria for women at high risk of mammography screening failures (interval invasive cancer or advanced cancer) have been identified. Mammography screening failure risk was evaluated among women undergoing supplemental ultrasound screening in clinical practice compared with women undergoing mammography alone. METHODS: A total of 38,166 screening ultrasounds and 825,360 screening mammograms without supplemental screening were identified during 2014-2020 within three Breast Cancer Surveillance Consortium (BCSC) registries. Risk of interval invasive cancer and advanced cancer were determined using BCSC prediction models. High interval invasive breast cancer risk was defined as heterogeneously dense breasts and BCSC 5-year breast cancer risk ≥2.5% or extremely dense breasts and BCSC 5-year breast cancer risk ≥1.67%. Intermediate/high advanced cancer risk was defined as BCSC 6-year advanced breast cancer risk ≥0.38%. RESULTS: A total of 95.3% of 38,166 ultrasounds were among women with heterogeneously or extremely dense breasts, compared with 41.8% of 825,360 screening mammograms without supplemental screening (p < .0001). Among women with dense breasts, high interval invasive breast cancer risk was prevalent in 23.7% of screening ultrasounds compared with 18.5% of screening mammograms without supplemental imaging (adjusted odds ratio, 1.35; 95% CI, 1.30-1.39); intermediate/high advanced cancer risk was prevalent in 32.0% of screening ultrasounds versus 30.5% of screening mammograms without supplemental screening (adjusted odds ratio, 0.91; 95% CI, 0.89-0.94). CONCLUSIONS: Ultrasound screening was highly targeted to women with dense breasts, but only a modest proportion were at high mammography screening failure risk. A clinically significant proportion of women undergoing mammography screening alone were at high mammography screening failure risk.

Digital mammography and digital breast tomosynthesis for detecting invasive lobular and ductal carcinoma.

PURPOSE: Invasive lobular carcinoma (ILC) is a distinct histological subtype of breast cancer that can make early detection with mammography challenging. We compared imaging performance of digital breast tomosynthesis (DBT) to digital mammography (DM) for diagnoses of ILC, invasive ductal carcinoma (IDC), and invasive mixed carcinoma (IMC) in a screening population. METHODS: We included screening exams (DM; n = 1,715,249 or DBT; n = 414,793) from 2011 to 2018 among 839,801 women in the Breast Cancer Surveillance Consortium. Examinations were followed for one year to ascertain incident ILC, IDC, or IMC. We measured cancer detection rate (CDR) and interval invasive cancer rate/1000 screening examinations for each histological subtype and stratified by breast density and modality. We calculated relative risk (RR) for DM vs. DBT using log-binomial models to adjust for the propensity of receiving DBT vs. DM. RESULTS: Unadjusted CDR per 1000 mammograms of ILC overall was 0.33 (95%CI: 0.30-0.36) for DM; 0.45 (95%CI: 0.39-0.52) for DBT, and for women with dense breasts- 0.33 (95%CI: 0.29-0.37) for DM and 0.54 (95%CI: 0.43-0.66) for DBT. Similar results were noted for IDC and IMC. Adjusted models showed a significantly increased RR for cancer detection with DBT compared to DM among women with dense breasts for all three histologies (RR; 95%CI: ILC 1.53; 1.09-2.14, IDC 1.21; 1.02-1.44, IMC 1.76; 1.30-2.38), but no significant increase among women with non-dense breasts. CONCLUSION: DBT was associated with higher CDR for ILC, IDC, and IMC for women with dense breasts. Early detection of ILC with DBT may improve outcomes for this distinct clinical entity.

Digital Breast Tomosynthesis versus Digital Mammography Screening Performance on Successive Screening Rounds from the Breast Cancer Surveillance Consortium.

Background Prior cross-sectional studies have observed that breast cancer screening with digital breast tomosynthesis (DBT) has a lower recall rate and higher cancer detection rate compared with digital mammography (DM). Purpose To evaluate breast cancer screening outcomes with DBT versus DM on successive screening rounds. Materials and Methods In this retrospective cohort study, data from 58 breast imaging facilities in the Breast Cancer Surveillance Consortium were collected. Analysis included women aged 40-79 years undergoing DBT or DM screening from 2011 to 2020. Absolute differences in screening outcomes by modality and screening round were estimated during the study period by using generalized estimating equations with marginal standardization to adjust for differences in women's risk characteristics across modality and round. Results A total of 523 485 DBT examinations (mean age of women, 58.7 years ± 9.7 [SD]) and 1 008 123 DM examinations (mean age, 58.4 years ± 9.8) among 504 863 women were evaluated. DBT and DM recall rates decreased with successive screening round, but absolute recall rates in each round were significantly lower with DBT versus DM (round 1 difference, -3.3% [95% CI: -4.6, -2.1] [P < .001]; round 2 difference, -1.8% [95% CI: -2.9, -0.7] [P = .003]; round 3 or above difference, -1.2% [95% CI: -2.4, -0.1] [P = .03]). DBT had significantly higher cancer detection (difference, 0.6 per 1000 examinations [95% CI: 0.2, 1.1]; P = .009) compared with DM only for round 3 and above. There were no significant differences in interval cancer rate (round 1 difference, 0.00 per 1000 examinations [95% CI: -0.24, 0.30] [P = .96]; round 2 or above difference, 0.04 [95% CI: -0.19, 0.31] [P = .76]) or total advanced cancer rate (round 1 difference, 0.00 per 1000 examinations [95% CI: -0.15, 0.19] [P = .94]; round 2 or above difference, -0.06 [95% CI: -0.18, 0.11] [P = .43]). Conclusion DBT had lower recall rates and could help detect more cancers than DM across three screening rounds, with no difference in interval or advanced cancer rates. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Skaane in this issue.

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.

Cost-Effectiveness of Screening Mammography Beyond Age 75 Years : A Cost-Effectiveness Analysis.

BACKGROUND: The cost-effectiveness of screening mammography beyond age 75 years remains unclear. OBJECTIVE: To estimate benefits, harms, and cost-effectiveness of extending mammography to age 80, 85, or 90 years according to comorbidity burden. DESIGN: Markov microsimulation model. DATA SOURCES: SEER (Surveillance, Epidemiology, and End Results) program and Breast Cancer Surveillance Consortium. TARGET POPULATION: U.S. women aged 65 to 90 years in groups defined by Charlson comorbidity score (CCS). TIME HORIZON: Lifetime. PERSPECTIVE: National health payer. INTERVENTION: Screening mammography to age 75, 80, 85, or 90 years. OUTCOME MEASURES: Breast cancer death, survival, and costs. RESULTS OF BASE-CASE ANALYSIS: Extending biennial mammography from age 75 to 80 years averted 1.7, 1.4, and 1.0 breast cancer deaths and increased days of life gained by 5.8, 4.2, and 2.7 days per 1000 women for comorbidity scores of 0, 1, and 2, respectively. Annual mammography beyond age 75 years was not cost-effective, but extending biennial mammography to age 80 years was ($54 000, $65 000, and $85 000 per quality-adjusted life-year [QALY] gained for women with CCSs of 0, 1, and ≥2, respectively). Overdiagnosis cases were double the number of deaths averted from breast cancer. RESULTS OF SENSITIVITY ANALYSIS: Costs per QALY gained were sensitive to changes in invasive cancer incidence and shift of breast cancer stage with screening mammography. LIMITATION: No randomized controlled trials of screening mammography beyond age 75 years are available to provide model parameter inputs. CONCLUSION: Although annual mammography is not cost-effective, biennial screening mammography to age 80 years is; however, the absolute number of deaths averted is small, especially for women with comorbidities. Women considering screening beyond age 75 years should weigh the potential harms of overdiagnosis versus the potential benefit of averting death from breast cancer. PRIMARY FUNDING SOURCE: National Cancer Institute and National Institutes of Health.

Breast cancer incidence among women with a family history of breast cancer by relative's age at diagnosis.

BACKGROUND: Women with a first-degree family history of breast cancer are often advised to begin screening when they are 10 years younger than the age at which their relative was diagnosed. Evidence is lacking to determine how much earlier they should begin. METHODS: Using Breast Cancer Surveillance Consortium data on screening mammograms from 1996 to 2016, the authors constructed a cohort of 306,147 women 30-59 years of age with information on first-degree family history of breast cancer and relative's age at diagnosis. The authors compared cumulative 5-year breast cancer incidence among women with and without a first-degree family history of breast by relative's age at diagnosis and by screening age. RESULTS: Among 306,147 women included in the study, approximately 11% reported a first-degree family history of breast cancer with 3885 breast cancer cases identified. Women reporting a relative diagnosed between 40 and 49 years and undergoing screening between ages 30 and 39 or 40 and 49 had similar 5-year cumulative incidences of breast cancer (respectively, 18.6/1000; 95% confidence interval [CI], 12.1, 25.7; 18.4/1000; 95% CI, 13.7, 23.5) as women without a family history undergoing screening between 50-59 years of age (18.0/1000; 95% CI, 17.0, 19.1). For relative's diagnosis age from 35 to 45 years of age, initiating screening 5-8 years before diagnosis age resulted in a 5-year cumulative incidence of breast cancer of 15.2/1000, that of an average 50-year-old woman. CONCLUSION: Women with a relative diagnosed at or before age 45 may wish to consider, in consultation with their provider, initiating screening 5-8 years earlier than their relative's diagnosis age.

Preoperative MRI in breast cancer: effect of breast density on biopsy rate and yield.

PURPOSE: Preoperative breast MRI is used to evaluate for additional cancer and extent of disease for newly diagnosed breast cancer, yet benefits and harms of preoperative MRI are not well-documented. We examined whether preoperative MRI yields additional biopsy and cancer detection by extent of breast density. METHODS: We followed women in the Breast Cancer Surveillance Consortium with an incident breast cancer diagnosed from 2005 to 2017. We quantified breast biopsies and cancers detected within 6 months of diagnosis by preoperative breast MRI receipt, overall and by breast density, accounting for MRI selection bias using inverse probability weighted logistic regression. RESULTS: Among 19,324 women with newly diagnosed breast cancer, 28% had preoperative MRI, 11% additional biopsy, and 5% additional cancer detected. Four times as many women with preoperative MRI underwent additional biopsy compared to women without MRI (22.6% v. 5.1%). Additional biopsy rates with preoperative MRI increased with increasing breast density (27.4% for extremely dense compared to 16.2% for almost entirely fatty breasts). Rates of additional cancer detection were almost four times higher for women with v. without MRI (9.9% v. 2.6%). Conditional on additional biopsy, age-adjusted rates of additional cancer detection were lowest among women with extremely dense breasts, regardless of imaging modality (with MRI: 35.0%; 95% CI 27.0-43.0%; without MRI: 45.1%; 95% CI 32.6-57.5%). CONCLUSION: For women with dense breasts, preoperative MRI was associated with much higher biopsy rates, without concomitant higher cancer detection. Preoperative MRI may be considered for some women, but selecting women based on breast density is not supported by evidence. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02980848; registered 2017.

Decision quality and regret with treatment decisions in women with breast cancer: Pre-operative breast MRI and breast density.

PURPOSE: We evaluated self-report of decision quality and regret with breast cancer surgical treatment by pre-operative breast MRI use in women recently diagnosed with breast cancer. METHODS: We conducted a survey with 957 women aged 18 + with stage 0-III breast cancer identified in the Breast Cancer Surveillance Consortium. Participants self-reported receipt of pre-operative breast MRI. Primary outcomes were process measures in the Breast Cancer Surgery Decision Quality Instrument (BCS-DQI) (continuous outcome) and Decision Regret Scale (dichotomized outcome as any/none). Generalized estimating equations with linear and logit link were used to estimate adjusted associations between breast MRI and primary outcomes. All analyses were also stratified by breast density. RESULTS: Survey participation rate was 27.9% (957/3430). Study population was primarily > 60 years, White, college educated, and diagnosed with early-stage breast cancer. Pre-operative breast MRI was reported in 46% of women. A higher proportion of women who were younger age (< 50 years), commercially insured, and self-detected their breast cancer reported pre-operative breast MRI use. In adjusted analysis, pre-operative breast MRI use compared with no use was associated with a small but statistically significantly higher decision quality scores (69.5 vs 64.7, p-value = 0.043). Decision regret did not significantly differ in women who reported pre-operative breast MRI use compared with no use (54.2% v. 48.7%, respectively, p-value = 0.11). Study results did not vary when stratified by breast density for either primary outcome. CONCLUSIONS AND RELEVANCE: Breast MRI use in the diagnostic work-up of breast cancer does not negatively alter women's perceptions of surgical treatment decisions in early survivorship. CLINICAL TRIALS REGISTRATION NUMBER: NCT03029286.

Comparing Mammographic Density Assessed by Digital Breast Tomosynthesis or Digital Mammography: The Breast Cancer Surveillance Consortium.

Background Consistency in reporting Breast Imaging Reporting and Data System (BI-RADS) breast density on mammograms is important because breast density is used for breast cancer risk assessment and is reported directly to women and clinicians to inform decisions about supplemental screening. Purpose To assess the consistency of BI-RADS density reporting between digital breast tomosynthesis (DBT) and digital mammography (DM) and evaluate density as a breast cancer risk factor when assessed using DM versus DBT. Materials and Methods The Breast Cancer Surveillance Consortium is a prospective cohort study of women undergoing mammography with DM or DBT. This secondary analysis included women aged 40-79 years who underwent at least two screening mammography examinations less than 36 months apart. Percentage agreement and κ statistic were estimated for pairs of BI-RADS density assessments. Cox proportional hazards regression was used to calculate hazard ratios (HRs) of breast density as a risk factor for invasive breast cancer. Results A total of 403 326 pairs of mammograms from 342 149 women were evaluated. There were no significant differences in breast density assessment in pairs consisting of one DM and one DBT examination (57 516 of 74 729 [77%]; κ = 0.64), two DM examinations (238 678 of 301 743 [79%]; κ = 0.67), and two DBT examinations (20 763 of 26 854 [77%]; κ = 0.65). Results were similar when restricting the analyses to pairs read by the same radiologist. The breast cancer HRs for breast density were similar for DM and DBT (P = .45 for interaction). The HRs for density acquired using DM and DBT, respectively, were 0.55 (95% CI: 0.49, 0.63) and 0.37 (95% CI: 0.21, 0.66) for almost entirely fat, 1.47 (95% CI: 1.37, 1.58) and 1.36 (95% CI: 1.02, 1.82) for heterogeneously dense, and 1.72 (95% CI: 1.54, 1.93) and 2.05 (95% CI: 1.25, 3.36) for extremely dense breasts. Conclusion Radiologist reporting of Breast Imaging Reporting and Data System density obtained with digital breast tomosynthesis did not differ from that obtained with digital mammography. © RSNA, 2021 Online supplemental material is available for this article.

Breast Biopsy Recommendations and Breast Cancers Diagnosed during the COVID-19 Pandemic.

Background The COVID-19 pandemic reduced mammography use, potentially delaying breast cancer diagnoses. Purpose To examine breast biopsy recommendations and breast cancers diagnosed before and during the COVID-19 pandemic by mode of detection (screen detected vs symptomatic) and women's characteristics. Materials and Methods In this secondary analysis of prospectively collected data, monthly breast biopsy recommendations after mammography, US, or both with subsequent biopsy performed were examined from 66 facilities of the Breast Cancer Surveillance Consortium between January 2019 and September 2020. The number of monthly and cumulative biopsies recommended and performed and the number of subsequent cancers diagnosed during the pandemic period (March 2020 to September 2020) were compared with data from the prepandemic period using Wald χ2 tests. Analyses were stratified by mode of detection and race or ethnicity. Results From January 2019 to September 2020, 17 728 biopsies were recommended and performed, with 6009 cancers diagnosed. From March to September 2020, there were substantially fewer breast biopsy recommendations with cancer diagnoses when compared with the same period in 2019 (1650 recommendations in 2020 vs 2171 recommendations in 2019 [24% fewer], P < .001), predominantly due to fewer screen-detected cancers (722 cancers in 2020 vs 1169 cancers in 2019 [38% fewer], P < .001) versus symptomatic cancers (895 cancers in 2020 vs 965 cancers in 2019 [7% fewer], P = .27). The decrease in cancer diagnoses was largest in Asian (67 diagnoses in 2020 vs 142 diagnoses in 2019 [53% fewer], P = .06) and Hispanic (82 diagnoses in 2020 vs 145 diagnoses in 2019 [43% fewer], P = .13) women, followed by Black women (210 diagnoses in 2020 vs 287 diagnoses in 2019 [27% fewer], P = .21). The decrease was smallest in non-Hispanic White women (1128 diagnoses in 2020 vs 1357 diagnoses in 2019 [17% fewer], P = .09). Conclusion There were substantially fewer breast biopsies with cancer diagnoses during the COVID-19 pandemic from March to September 2020 compared with the same period in 2019, with Asian and Hispanic women experiencing the largest declines, followed by Black women. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Heller in this issue.

Trends in Annual Surveillance Mammography Participation Among Breast Cancer Survivors From 2004 to 2016.

BACKGROUND: Annual mammography is recommended for breast cancer survivors; however, population-level temporal trends in surveillance mammography participation have not been described. Our objective was to characterize trends in annual surveillance mammography participation among women with a personal history of breast cancer over a 13-year period. METHODS: We examined annual surveillance mammography participation from 2004 to 2016 in a nationwide sample of commercially insured women with prior breast cancer. Rates were stratified by age group (40-49 vs 50-64 years), visit with a surgical/oncology specialist or primary care provider within the prior year, and sociodemographic characteristics. Joinpoint models were used to estimate annual percentage changes (APCs) in participation during the study period. RESULTS: Among 141,672 women, mammography rates declined from 74.1% in 2004 to 67.1% in 2016. Rates were stable from 2004 to 2009 (APC, 0.1%; 95% CI, -0.5% to 0.8%) but declined 1.5% annually from 2009 to 2016 (95% CI, -1.9% to -1.1%). For women aged 40 to 49 years, rates declined 2.8% annually (95% CI, -3.4% to -2.1%) after 2009 versus 1.4% annually in women aged 50 to 64 years (95% CI, -1.9% to -1.0%). Similar trends were observed in women who had seen a surgeon/oncologist (APC, -1.7%; 95% CI, -2.1% to -1.4%) or a primary care provider (APC, -1.6%; 95% CI, -2.1% to -1.2%) in the prior year. CONCLUSIONS: Surveillance mammography participation among breast cancer survivors declined from 2009 to 2016, most notably among women aged 40 to 49 years. These findings highlight a need for focused efforts to improve adherence to surveillance and prevent delays in detection of breast cancer recurrence and second cancers.

Mammography adherence in relation to function-related indicators in older women.

Prior studies of screening mammography patterns by functional status in older women show inconsistent results. We used Breast Cancer Surveillance Consortium-Medicare linked data (1999-2014) to investigate the association of functional limitations with adherence to screening mammography in 145,478 women aged 66-74 years. Functional limitation was represented by a claims-based function-related indicator (FRI) score which incorporated 16 items reflecting functional status. Baseline adherence was defined as mammography utilization 9-30 months after the index screening mammography. Longitudinal adherence was examined among women adherent at baseline and defined as time from the index mammography to end of the first 30-month gap in mammography. Multivariable logistic regression and Cox proportional hazards models were used to investigate baseline and longitudinal adherence, respectively. Subgroup analyses were conducted by age (66-70 vs. 71-74 years). Overall, 69.6% of participants had no substantial functional limitation (FRI score 0), 23.5% had some substantial limitations (FRI score 1), and 6.8% had serious limitations (FRI score ≥ 2). Mean age at baseline was 68.5 years (SD = 2.6), 85.3% of participants were white, and 77.1% were adherent to screening mammography at baseline. Women with a higher FRI score were more likely to be non-adherent at baseline (FRI ≥ 2 vs. 0: aOR = 1.13, 95% CI = 1.06, 1.20, p-trend < 0.01). Similarly, a higher FRI score was associated with longitudinal non-adherence (FRI ≥ 2 vs. 0: aHR = 1.16, 95% CI = 1.11, 1.22, p-trend < 0.01). Effect measures of FRI did not differ substantially by age categories. Older women with a higher burden of functional limitations are less likely to be adherent to screening mammography recommendations.

Association of Screening With Digital Breast Tomosynthesis vs Digital Mammography With Risk of Interval Invasive and Advanced Breast Cancer.

Importance: Digital breast tomosynthesis (DBT) was developed with the expectation of improving cancer detection in women with dense breasts. Studies are needed to evaluate interval invasive and advanced breast cancer rates, intermediary outcomes related to breast cancer mortality, by breast density and breast cancer risk. Objective: To evaluate whether DBT screening is associated with a lower likelihood of interval invasive cancer and advanced breast cancer compared with digital mammography by extent of breast density and breast cancer risk. Design, Setting, and Participants: Cohort study of 504 427 women aged 40 to 79 years who underwent 1 003 900 screening digital mammography and 375 189 screening DBT examinations from 2011 through 2018 at 44 US Breast Cancer Surveillance Consortium (BCSC) facilities with follow-up for cancer diagnoses through 2019 by linkage to state or regional cancer registries. Exposures: Breast Imaging Reporting and Data System (BI-RADS) breast density; BCSC 5-year breast cancer risk. Main Outcomes and Measures: Rates per 1000 examinations of interval invasive cancer within 12 months of screening mammography and advanced breast cancer (prognostic pathologic stage II or higher) within 12 months of screening mammography, both estimated with inverse probability weighting. Results: Among 504 427 women in the study population, the median age at time of mammography was 58 years (IQR, 50-65 years). Interval invasive cancer rates per 1000 examinations were not significantly different for DBT vs digital mammography (overall, 0.57 vs 0.61, respectively; difference, -0.04; 95% CI, -0.14 to 0.06; P = .43) or among all the 836 250 examinations with BCSC 5-year risk less than 1.67% (low to average-risk) or all the 413 061 examinations with BCSC 5-year risk of 1.67% or higher (high risk) across breast density categories. Advanced cancer rates were not significantly different for DBT vs digital mammography among women at low to average risk or at high risk with almost entirely fatty, scattered fibroglandular densities, or heterogeneously dense breasts. Advanced cancer rates per 1000 examinations were significantly lower for DBT vs digital mammography for the 3.6% of women with extremely dense breasts and at high risk of breast cancer (13 291 examinations in the DBT group and 31 300 in the digital mammography group; 0.27 vs 0.80 per 1000 examinations; difference, -0.53; 95% CI, -0.97 to -0.10) but not for women at low to average risk (10 611 examinations in the DBT group and 37 796 in the digital mammography group; 0.54 vs 0.42 per 1000 examinations; difference, 0.12; 95% CI, -0.09 to 0.32). Conclusions and Relevance: Screening with DBT vs digital mammography was not associated with a significant difference in risk of interval invasive cancer and was associated with a significantly lower risk of advanced breast cancer among the 3.6% of women with extremely dense breasts and at high risk of breast cancer. No significant difference was observed in the 96.4% of women with nondense breasts, heterogeneously dense breasts, or with extremely dense breasts not at high risk.

Association of mammographic density measures and breast cancer "intrinsic" molecular subtypes.

PURPOSE: We evaluated the association of percent mammographic density (PMD), absolute dense area (DA), and non-dense area (NDA) with risk of "intrinsic" molecular breast cancer (BC) subtypes. METHODS: We pooled 3492 invasive BC and 10,148 controls across six studies with density measures from prediagnostic, digitized film-screen mammograms. We classified BC tumors into subtypes [63% Luminal A, 21% Luminal B, 5% HER2 expressing, and 11% as triple negative (TN)] using information on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. We used polytomous logistic regression to calculate odds ratio (OR) and 95% confidence intervals (CI) for density measures (per SD) across the subtypes compared to controls, adjusting for age, body mass index and study, and examined differences by age group. RESULTS: All density measures were similarly associated with BC risk across subtypes. Significant interaction of PMD by age (P = 0.001) was observed for Luminal A tumors, with stronger effect sizes seen for younger women < 45 years (OR = 1.69 per SD PMD) relative to women of older ages (OR = 1.53, ages 65-74, OR = 1.44 ages 75 +). Similar but opposite trends were seen for NDA by age for risk of Luminal A: risk for women: < 45 years (OR = 0.71 per SD NDA) was lower than older women (OR = 0.83 and OR = 0.84 for ages 65-74 and 75 + , respectively) (P < 0.001). Although not significant, similar patterns of associations were seen by age for TN cancers. CONCLUSIONS: Mammographic density measures were associated with risk of all "intrinsic" molecular subtypes. However, findings of significant interactions between age and density measures may have implications for subtype-specific risk models.

Deep Learning Predicts Interval and Screening-detected Cancer from Screening Mammograms: A Case-Case-Control Study in 6369 Women.

Background The ability of deep learning (DL) models to classify women as at risk for either screening mammography-detected or interval cancer (not detected at mammography) has not yet been explored in the literature. Purpose To examine the ability of DL models to estimate the risk of interval and screening-detected breast cancers with and without clinical risk factors. Materials and Methods This study was performed on 25 096 digital screening mammograms obtained from January 2006 to December 2013. The mammograms were obtained in 6369 women without breast cancer, 1609 of whom developed screening-detected breast cancer and 351 of whom developed interval invasive breast cancer. A DL model was trained on the negative mammograms to classify women into those who did not develop cancer and those who developed screening-detected cancer or interval invasive cancer. Model effectiveness was evaluated as a matched concordance statistic (C statistic) in a held-out 26% (1669 of 6369) test set of the mammograms. Results The C statistics and odds ratios for comparing patients with screening-detected cancer versus matched controls were 0.66 (95% CI: 0.63, 0.69) and 1.25 (95% CI: 1.17, 1.33), respectively, for the DL model, 0.62 (95% CI: 0.59, 0.65) and 2.14 (95% CI: 1.32, 3.45) for the clinical risk factors with the Breast Imaging Reporting and Data System (BI-RADS) density model, and 0.66 (95% CI: 0.63, 0.69) and 1.21 (95% CI: 1.13, 1.30) for the combined DL and clinical risk factors model. For comparing patients with interval cancer versus controls, the C statistics and odds ratios were 0.64 (95% CI: 0.58, 0.71) and 1.26 (95% CI: 1.10, 1.45), respectively, for the DL model, 0.71 (95% CI: 0.65, 0.77) and 7.25 (95% CI: 2.94, 17.9) for the risk factors with BI-RADS density (b rated vs non-b rated) model, and 0.72 (95% CI: 0.66, 0.78) and 1.10 (95% CI: 0.94, 1.29) for the combined DL and clinical risk factors model. The P values between the DL, BI-RADS, and combined model's ability to detect screen and interval cancer were .99, .002, and .03, respectively. Conclusion The deep learning model outperformed in determining screening-detected cancer risk but underperformed for interval cancer risk when compared with clinical risk factors including breast density. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Bae and Kim in this issue.

Digital Mammography and Breast Tomosynthesis Performance in Women with a Personal History of Breast Cancer, 2007-2016.

Background Since 2007, digital mammography and digital breast tomosynthesis (DBT) replaced screen-film mammography. Whether these technologic advances have improved diagnostic performance has, to the knowledge of the authors, not yet been established. Purpose To evaluate the performance and outcomes of surveillance mammography (digital mammography and DBT) performed from 2007 to 2016 in women with a personal history of breast cancer and compare with data from 1996 to 2007 and the performance of digital mammography screening benchmarks. Materials and Methods In this observational cohort study, five Breast Cancer Surveillance Consortium registries provided prospectively collected mammography data linked with tumor registry and pathologic outcomes. This study identified asymptomatic women with American Joint Committee on Cancer anatomic stages 0-III primary breast cancer who underwent surveillance mammography from 2007 to 2016. The primary outcome was a second breast cancer diagnosis within 1 year of mammography. Performance measures included the recall rate, cancer detection rate, interval cancer rate, positive predictive value of biopsy recommendation, sensitivity, and specificity. Results Among 32 331 women who underwent 117 971 surveillance mammographic examinations (112 269 digital mammographic examinations and 5702 DBT examinations), the mean age at initial diagnosis was 59 years ± 12 (standard deviation). Of 1418 second breast cancers diagnosed, 998 were surveillance-detected cancers and 420 were interval cancers. The recall rate was 8.8% (10 365 of 117 971; 95% CI: 8.6%, 9.0%), the cancer detection rate was 8.5 per 1000 examinations (998 of 117 971; 95% CI: 8.0, 9.0), the interval cancer rate was 3.6 per 1000 examinations (420 of 117 971; 95% CI: 3.2, 3.9), the positive predictive value of biopsy recommendation was 31.0% (998 of 3220; 95% CI: 29.4%, 32.7%), the sensitivity was 70.4% (998 of 1418; 95% CI: 67.9%, 72.7%), and the specificity was 98.1% (114 331 of 116 553; 95% CI: 98.0%, 98.2%). Compared with previously published studies, interval cancer rate was comparable with rates from 1996 to 2007 in women with a personal history of breast cancer and was higher than the published digital mammography screening benchmarks. Conclusion In transitioning from screen-film to digital mammography and digital breast tomosynthesis, surveillance mammography performance demonstrated minimal improvement over time and remained inferior to the performance of screening mammography benchmarks. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Moy and Gao in this issue.