Timely follow-up of positive cancer screening results: A systematic review and recommendations from the PROSPR Consortium.

Timely follow-up for positive cancer screening results remains suboptimal, and the evidence base to inform decisions on optimizing the timeliness of diagnostic testing is unclear. This systematic review evaluated published studies regarding time to follow-up after a positive screening for breast, cervical, colorectal, and lung cancers. The quality of available evidence was very low or low across cancers, with potential attenuated or reversed associations from confounding by indication in most studies. Overall, evidence suggested that the risk for poorer cancer outcomes rises with longer wait times that vary within and across cancer types, which supports performing diagnostic testing as soon as feasible after the positive result, but evidence for specific time targets is limited. Within these limitations, we provide our opinion on cancer-specific recommendations for times to follow-up and how existing guidelines relate to the current evidence. Thresholds set should consider patient worry, potential for loss to follow-up with prolonged wait times, and available resources. Research is needed to better guide the timeliness of diagnostic follow-up, including considerations for patient preferences and existing barriers, while addressing methodological weaknesses. Research is also needed to identify effective interventions for reducing wait times for diagnostic testing, particularly in underserved or low-resource settings. CA Cancer J Clin 2018;68:199-216. © 2018 American Cancer Society.

Feasibility of risk assessment for breast cancer molecular subtypes.

PURPOSE: Few breast cancer risk assessment models account for the risk profiles of different tumor subtypes. This study evaluated whether a subtype-specific approach improves discrimination. METHODS: Among 3389 women who had a screening mammogram and were later diagnosed with invasive breast cancer we performed multinomial logistic regression with tumor subtype as the outcome and known breast cancer risk factors as predictors. Tumor subtypes were defined by expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) based on immunohistochemistry. Discrimination was assessed with the area under the receiver operating curve (AUC). Absolute risk of each subtype was estimated by proportioning Gail absolute risk estimates by the predicted probabilities for each subtype. We then compared risk factor distributions for women in the highest deciles of risk for each subtype. RESULTS: There were 3,073 ER/PR+ HER2 - , 340 ER/PR +HER2 + , 126 ER/PR-ER2+, and 300 triple-negative breast cancers (TNBC). Discrimination differed by subtype; ER/PR-HER2+ (AUC: 0.64, 95% CI 0.59, 0.69) and TNBC (AUC: 0.64, 95% CI 0.61, 0.68) had better discrimination than ER/PR+HER2+ (AUC: 0.61, 95% CI 0.58, 0.64). Compared to other subtypes, patients at high absolute risk of TNBC were younger, mostly Black, had no family history of breast cancer, and higher BMI. Those at high absolute risk of HER2+ cancers were younger and had lower BMI. CONCLUSION: Our study provides proof of concept that stratifying risk prediction for breast cancer subtypes may enable identification of patients with unique profiles conferring increased risk for tumor subtypes.

A constrained maximum likelihood approach to developing well-calibrated models for predicting binary outcomes.

The added value of candidate predictors for risk modeling is routinely evaluated by comparing the performance of models with or without including candidate predictors. Such comparison is most meaningful when the estimated risk by the two models are both unbiased in the target population. Very often data for candidate predictors are sourced from nonrepresentative convenience samples. Updating the base model using the study data without acknowledging the discrepancy between the underlying distribution of the study data and that in the target population can lead to biased risk estimates and therefore an unfair evaluation of candidate predictors. To address this issue assuming access to a well-calibrated base model, we propose a semiparametric method for model fitting that enforces good calibration. The central idea is to calibrate the fitted model against the base model by enforcing suitable constraints in maximizing the likelihood function. This approach enables unbiased assessment of model improvement offered by candidate predictors without requiring a representative sample from the target population, thus overcoming a significant practical challenge. We study theoretical properties for model parameter estimates, and demonstrate improvement in model calibration via extensive simulation studies. Finally, we apply the proposed method to data extracted from Penn Medicine Biobank to inform the added value of breast density for breast cancer risk assessment in the Caucasian woman population.

Changes in mammographic density and risk of breast cancer among a diverse cohort of women undergoing mammography screening.

PURPOSE: Mammographic density (MD) is a strong breast cancer risk factor. MD may change over time, with potential implications for breast cancer risk. Few studies have assessed associations between MD change and breast cancer in racially diverse populations. We investigated the relationships between MD and MD change over time and breast cancer risk in a large, diverse screening cohort. MATERIALS AND METHODS: We retrospectively analyzed data from 8462 women who underwent ≥ 2 screening mammograms from Sept. 2010 to Jan. 2015 (N = 20,766 exams); 185 breast cancers were diagnosed 1-7 years after screening. Breast percent density (PD) and dense area (DA) were estimated from raw digital mammograms (Hologic Inc.) using LIBRA (v1.0.4). For each MD measure, we modeled breast density change between two sequential visits as a function of demographic and risk covariates. We used Cox regression to examine whether varying degrees of breast density change were associated with breast cancer risk, accounting for multiple exams per woman. RESULTS: PD at any screen was significantly associated with breast cancer risk (hazard ratio (HR) for PD = 1.03 (95% CI [1.01, 1.05], p < 0.0005), but neither change in breast density nor more extreme than expected changes in breast density were associated with breast cancer risk. We found no evidence of differences in density change or breast cancer risk due to density change by race. Results using DA were essentially identical. CONCLUSIONS: Using a large racially diverse cohort, we found no evidence of association between short-term change in MD and risk of breast cancer, suggesting that short-term MD change is not a strong predictor for risk.

Nationwide Trends and Determinants of Germline BRCA1/2 Testing in Patients With Breast and Ovarian Cancer.

BACKGROUND: Germline genetic testing (GT) for BRCA1/2 is instrumental in identifying patients with breast and ovarian cancers who are eligible for PARP inhibitors (PARPi). Little is known about recent trends and determinants of GT since PARPi were approved for these patients. PATIENTS AND METHODS: We performed a retrospective cohort study of patients in a nationwide electronic health record (EHR)-derived oncology-specific database with the following GT eligibility criteria: breast cancer diagnosed at age ≤45 years, triple-negative breast cancer diagnosed at age ≤60 years, male breast cancer, or ovarian cancer. GT within 1 year of diagnosis was assessed and stratified by tumor type. Multivariable log-binomial regressions estimated adjusted relative risks (RRs) of GT by patient and tumor characteristics. RESULTS: Among 2,982 eligible patients with breast cancer, 56.4% underwent GT between January 2011 and March 2020, with a significant increase in GT over time (RR, 1.08; 95% CI, 1.05-1.11, for each year), independent of when PARPi were approved for BRCA1/2-mutated metastatic breast cancer in January 2018. In multivariable analyses, older age (RR, 0.93; 95% CI, 0.90-0.96, for every 5 years) and Medicare coverage (RR, 0.69; 95% CI, 0.49-0.96 vs commercial insurance) were associated with less GT. Among 5,563 eligible patients with ovarian cancer, 35.4% underwent GT between January 2011 and March 2020, with a significant increase in GT over time (RR, 1.11; 95% CI, 1.07-1.14, for each year) that accelerated after approval of PARPi for BRCA1/2-mutated, chemotherapy-refractory ovarian cancer in December 2014 (RR, 1.42; 95% CI, 1.19-1.70). Older age (RR, 0.95; 95% CI, 0.93-0.97, for every 5 years) and Black or African American race (RR, 0.80; 95% CI, 0.65-0.98 vs White race) were associated with less GT. CONCLUSIONS: GT remains underutilized nationwide among patients with breast and ovarian cancers. Although GT has increased over time, significant disparities by age, race, and insurance status persist. Additional work is needed to design, implement, and evaluate strategies to ensure that all eligible patients receive GT.

Breast cancer polygenic risk scores are associated with short-term risk of poor prognosis breast cancer.

PURPOSE: Polygenic risk scores (PRS) for breast cancer may help guide screening decisions. However, few studies have examined whether PRS are associated with risk of short-term or poor prognosis breast cancers. The study purpose was to evaluate the association of the 313 SNP breast cancer PRS with 2-year risk of poor prognosis breast cancer. METHODS: We evaluated the association of breast cancer PRS with breast cancer overall, ER + and ER- breast cancer, and poor prognosis breast cancer diagnosed within 2 years of a negative mammogram among a cohort of 3657 women using logistic regression adjusted for age, breast density, race/ethnicity, year of screening, and genetic ancestry principal components. Breast cancers were considered poor prognosis if they were metastatic, positive lymph nodes, ER/PR + HER2- and > 2 cm, ER/PR/HER2-, or HER2 + and > 1 cm. RESULTS: Of the 308 breast cancers, 137 (44%) were poor prognosis. The overall breast cancer PRS was significantly associated with breast cancer diagnosis within 2 years (OR 1.39, 95% CI 1.23-1.57, p < 0.001). The breast cancer PRS was also associated specifically with diagnosis of poor prognosis disease (OR 1.24, 95% CI 1.03-1.49, p = 0.018), but was more strongly associated with good prognosis cancer (OR 1.52 95% CI 1.29-1.80 p = 3.60 × 10-7) The ER + PRS was significantly associated with ER/PR + breast cancer (OR 1.41, 95% CI 1.24-1.61, p < 0.001) and the ER- PRS was significantly associated with ER- breast cancer (OR 1.48, 95% CI 1.08-2.02, p = 0.015). CONCLUSION: Breast cancer PRS was independently and significantly associated with diagnosis of both breast cancer overall and poor prognosis breast cancer within 2 years of a negative mammogram, suggesting PRS may help guide decisions about screening intervals and supplemental screening.

Risk factors for an advanced breast cancer diagnosis within 2 years of a negative mammogram.

BACKGROUND: Identifying women at risk for advanced interval cancers would allow better targeting of mammography and supplemental screening. The authors assessed risk factors for advanced breast cancer within 2 years of a negative mammogram. METHODS: The authors included 293,520 negative mammograms performed from 2006 to 2015 among 74,736 women. Breast cancers were defined as advanced if they were >2 cm, were >1 cm and triple-negative or human epidermal growth factor receptor 2-positive, had positive lymph nodes, or were metastatic. Cox proportional hazards modeling was used to evaluate associations of age, breast density, menopause, mammogram type, prior breast biopsy, body mass index (BMI), and a family history of breast cancer with a cancer diagnosis within 2 years of a negative mammogram. Models were stratified by year since a negative mammogram. RESULTS: Among 1345 breast cancers, 357 were advanced (26.5%), and 988 (73.5%) were at an early stage. Breast density, prior biopsy, and family history were associated with an increased risk of both advanced and early-stage cancers. Overweight and obese women had a 40% higher risk of early-stage cancer only in year 2 (overweight hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.19-1.67; P < .001; obese HR, 1.41; 95% CI, 1.17-1.70; P < .001). Obese women had a 90% increased risk of advanced cancer in year 1 (HR, 1.90; 95% CI, 1.14-3.18; P = .014), and both overweight and obese women had a 40% or greater increased risk in year 2 (overweight HR, 1.55; 95% CI, 1.14-2.07; P = .005; obese HR, 1.42; 95% CI, 1.00-2.01; P = .051). CONCLUSIONS: A higher BMI was associated with an advanced breast cancer diagnosis within 2 years of a negative mammogram. These results have important implications for risk assessment, screening intervals, and use of supplemental screening.

Risk factors for breast cancer subtypes among Black women undergoing screening mammography.

PURPOSE: Black women are more likely than non-Hispanic White women to be diagnosed with triple negative breast cancer (TNBC), an aggressive subtype with limited treatment options. The study objective was to evaluate the associations of known breast cancer risk factors, including breast density, with TNBC among Black women. METHODS: This study included Black women who underwent screening mammography between the ages of 40-84 years at a University of Pennsylvania Health System between 2010 and 2015. Cox proportional hazard models using multiple imputation with chained equations were used to estimate hazard ratios and 95% confidence intervals for risk factors for ER/PR+/HER2- and TNBC. RESULTS: Among 25,013 Black women, there were 330 incident breast cancers (1.3%) during a mean follow-up of 5.8 years; 218 (66.1%) ER/PR+ HER- and 61 (18.1%) TNBC. Having dense breasts (heterogeneously dense or extremely dense) vs. non-dense breasts (almost entirely fatty or scattered areas of fibroglandular density) increased risk of ER/PR+/HER2- breast cancer almost 80% (HR 1.79, 95% CI 1.32-2.43) and TNBC more than twofold (HR 2.53, 1.45-4.44). Older age was associated with an increased risk for ER/PR+/HER2- (HR 1.04, 1.03-1.06) and TNBC (HR 1.03, 1.00-1.05). Having a BMI of > 30 kg/m2 was associated with an increased risk (HR 2.77, 1.05-7.30) for TNBC and an increased risk of ERPR+/HER2- breast cancer in postmenopausal but not pre-menopausal women (p-interaction = 0.016). CONCLUSION: Our results suggest that breast density and obesity are strong risk factors for TNBC among Black women. Understanding breast cancer subtype specific risk factors among Black women can help improve risk assessment.

Imaging Surveillance of Breast Cancer Survivors with Digital Mammography versus Digital Breast Tomosynthesis.

Background Among breast cancer survivors, detecting a breast cancer when it is asymptomatic (rather than symptomatic) improves survival; thus, imaging surveillance in these patients is warranted. Digital breast tomosynthesis (DBT) is used for screening, but data on DBT for surveillance in this high-risk population are limited. Purpose To determine whether DBT leads to improved screening performance metrics when compared with two-dimensional digital mammography among breast cancer survivors. Materials and Methods In this study, screening mammograms obtained in breast cancer survivors before and after DBT implementation were retrospectively reviewed (March 2008-February 2011 for the digital mammography group; January 2013-December 2017 for the DBT group). Mammograms were interpreted by breast imaging radiologists with the assistance of computer-aided detection. Performance metrics and tumor characteristics between the groups were compared using multivariable logistic regression models. Results The digital mammography and DBT groups were composed of 9019 and 22 887 mammographic examinations, respectively, in 8170 women (mean age, 62 years ± 12 [standard deviation]). In the DBT group, the abnormal interpretation rate was lower (5.8% [1331 of 22 887 examinations] vs 6.2% [563 of 9019 examinations]; odds ratio [OR], 0.80; 95% CI: 0.71, 0.91; P = .001) and specificity was higher (95.0% [21 502 of 22 644 examinations] vs 94.7% [8424 of 8891 examinations]; OR, 1.23; 95% CI: 1.07, 1.41; P = .003) than in the digital mammography group. The cancer detection rates did not differ (8.3 per 1000 examinations with DBT vs 10.6 with digital mammography; OR, 0.76; 95% CI: 0.57, 1.02; P = .07). The proportions of screening-detected invasive cancers, versus in situ cancers, were similar (74% [140 of 189 cancers] in the DBT group vs 72% [69 of 96 cancers] in the digital mammography group; P = .69). Of 86 interval cancers, 58% (50 of 86 cancers) manifested with symptoms, and 33% (28 of 86 cancers) were detected at screening MRI. Conclusion Among breast cancer survivors, screening with digital breast tomosynthesis led to fewer false-positive results and higher specificity but did not affect cancer detection. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Hooley and Butler in this issue.

Clinical and sociodemographic factors associated with late stage cervical cancer diagnosis in Botswana.

BACKGROUND: Cervical cancer is the leading cause of female cancer mortality in Botswana with the majority of cervical cancer patients presenting with late-stage disease. The identification of factors associated with late-stage disease could reduce the cervical cancer burden. This study aims to identify potential patient level clinical and sociodemographic factors associated with a late-stage diagnosis of cervical cancer in Botswana in order to help inform future interventions at the community and individual levels to decrease cervical cancer morbidity and mortality. RESULTS: There were 984 women diagnosed with cervical cancer from January 2015 to March 2020 at two tertiary hospitals in Gaborone, Botswana. Four hundred forty women (44.7%) presented with late-stage cervical cancer, and 674 women (69.7%) were living with HIV. The mean age at diagnosis was 50.5 years. The association between late-stage (III/IV) cervical cancer at diagnosis and patient clinical and sociodemographic factors was evaluated using multivariable logistic regression with multiple imputation. Women who reported undergoing cervical cancer screening had lower odds of late-stage disease at diagnosis (OR: 0.63, 95% CI 0.47-0.84) compared to those who did not report screening. Women who had never been married had increased odds of late-stage disease at diagnosis (OR: 1.35, 95% CI 1.02-1.86) compared to women who had been married. Women with abnormal vaginal bleeding had higher odds of late-stage disease at diagnosis (OR: 2.32, 95% CI 1.70-3.16) compared to those without abnormal vaginal bleeding. HIV was not associated with a diagnosis of late-stage cervical cancer. Rural women who consulted a traditional healer had increased odds of late-stage disease at diagnosis compared to rural women who had never consulted a traditional healer (OR: 1.61, 95% CI 1.02-2.55). CONCLUSION: Increasing education and awareness among women, regardless of their HIV status, and among providers, including traditional healers, about the benefits of cervical cancer screening and about the importance of seeking prompt medical care for abnormal vaginal bleeding, while also developing support systems for unmarried women, may help reduce cervical cancer morbidity and mortality in Botswana.

Breast Cancer Screening with Digital Breast Tomosynthesis: Are Initial Benefits Sustained?

Background Performance metrics with digital breast tomosynthesis (DBT) are based on early experiences. There is limited research on whether the benefits of DBT are sustained. Purpose To determine whether improved screening performance metrics with DBT are sustained over time at the population level and after the first screening round at the individual level. Materials and Methods A retrospective review was conducted of screening mammograms that had been obtained before DBT implementation (March 2008 to February 2011, two-dimensional digital mammography [DM] group) and for 5 years after implementation (January 2013 to December 2017, DBT1-DBT5 groups, respectively). Patients who underwent DBT were also categorized according to the number of previous DBT examinations they had undergone. Performance metrics were compared between DM and DBT groups and between patients with no previous DBT examinations and those with at least one prior DBT examination by using multivariable logistic regression models. Results The DM group consisted of 99 582 DM examinations in 55 086 women (mean age, 57.3 years ± 11.6 [standard deviation]). The DBT group consisted of 205 048 examinations in 76 276 women (mean age, 58.2 years ± 11.2). There were no differences in the cancer detection rate (CDR) between DM and DBT groups (4.6-5.8 per 1000 examinations, P = .08 to P = .95). The highest CDR was observed with a woman's first DBT examination (6.1 per 1000 examinations vs 4.4-5.7 per 1000 examinations with at least one prior DBT examination, P = .001 to P = .054). Compared with the DM group, the DBT1 group had a lower abnormal interpretation rate (AIR) (adjusted odds ratio [AOR], 0.85; P < .001), which remained reduced in the DBT2, DBT3, and DBT5 groups (P < .001 to P = .02). The reduction in AIR was also sustained after the first examination (P < .001 to P = .002). Compared with the DM group, the DBT1 group had a higher specificity (AOR, 1.20; P < .001), which remained increased in DBT2, DBT3, and DBT5 groups (P < .001 to P = .004). The increase in specificity was also sustained after the first examination (P < .001 to P = .01). Conclusion The benefits of reduced false-positive examinations and higher specificity with screening tomosynthesis were sustained after the first screening round at the individual level. © RSNA, 2020 See also the editorial by Taourel in this issue.

Different associations of tumor PIK3CA mutations and clinical outcomes according to aspirin use among women with metastatic hormone receptor positive breast cancer.

INTRODUCTION: The relationships among PIK3CA mutations, medication use and tumor progression remains poorly understood. Aspirin use post-diagnosis may modify components of the PI3K pathway, including AKT and mTOR, and has been associated with lower risk of breast cancer recurrence and mortality. We assessed time to metastasis (TTM) and survival with respect to aspirin use and tumor PIK3CA mutations among women with metastatic breast cancer. METHODS: Patients with hormone receptor positive, HER2 negative (HR+/HER2-) metastatic breast cancer treated in 2009-2016 who received tumor genotyping were included. Aspirin use between primary and metastatic diagnosis was extracted from electronic medical records. TTM and survival were estimated using Cox proportional hazards regression. RESULTS: Among 267 women with metastatic breast cancer, women with PIK3CA mutated tumors had longer TTM than women with PIK3CA wildtype tumors (7.1 vs. 4.7 years, p = 0.008). There was a significant interaction between PIK3CA mutations and aspirin use on TTM (p = 0.006) and survival (p = 0.026). PIK3CA mutations were associated with longer TTM among aspirin non-users (HR = 0.60 95% CI:0.44-0.82 p = 0.001) but not among aspirin users (HR = 1.57 0.86-2.84 p = 0.139). Similarly, PIK3CA mutations were associated with reduced mortality among aspirin non-users (HR = 0.70 95% CI:0.48-1.02 p = 0.066) but not among aspirin users (HR = 1.75 95% CI:0.88-3.49 p = 0.110). CONCLUSIONS: Among women who develop metastatic breast cancer, tumor PIK3CA mutations are associated with slower time to progression and mortality only among aspirin non-users. Larger studies are needed to confirm this finding and examine the relationship among aspirin use, tumor mutation profile, and the overall risk of breast cancer progression.

Digital 2D versus Tomosynthesis Screening Mammography among Women Aged 65 and Older in the United States.

Background Although breast cancer incidence and mortality rates increase with advancing age, there are limited data on the benefits and risks of screening mammography in older women and on the performance of two-dimensional digital mammography (DM) and digital breast tomosynthesis (DBT) in older women. Purpose To compare performance metrics of DM and DBT among women aged 65 years and older. Materials and Methods For this retrospective study, consecutive screening mammograms in patients aged 65 years and older from March 2008 to February 2011 (DM group) and from January 2013 to December 2015 (DBT group) were reviewed. Cancer detection rate, abnormal interpretation rate, positive predictive values, sensitivity, and specificity were calculated. Multivariable logistic regression models were fit to compare performance metrics in the DM versus DBT groups. Results The DM group had 15 019 women (mean age ± standard deviation, 72.7 years ± 6.3), and the DBT group had 20 646 women (mean age, 72.1 years ± 5.9). After adjusting for multiple variables, there was no difference in cancer detection rate between the DM and DBT groups (6.9 vs 8.2 per 1000 examinations; adjusted odds ratio [AOR], 1.13; P = .23). Compared with the DM group, the DBT group had a lower abnormal interpretation rate (5.7% vs 5.8%; AOR, 0.88; P < .001), higher positive predictive value 1 (14.5% vs 11.9%; AOR, 1.26; P = .03), and higher specificity (95.1% vs 94.8%; AOR, 1.18; P < .001). The DBT group had a higher proportion of invasive cancers relative to in situ cancers (81.1% vs 74.4%; P = .06) and fewer node-positive cancers (10.2% vs 16.6%; P = .054) than did the DM group. Conclusion In women aged 65 years and older, integration of digital breast tomosynthesis led to improved performance metrics, with a lower abnormal interpretation rate, higher positive predictive value 1, and higher specificity. © RSNA, 2019 See also the editorial by Philpotts and Durand in this issue.

Effect of Mammographic Screening Modality on Breast Density Assessment: Digital Mammography versus Digital Breast Tomosynthesis.

Background Breast Imaging Reporting and Data System (BI-RADS) breast density categories assigned by interpreting radiologists often influence decisions surrounding supplemental breast cancer screening and risk assessment. The landscape of mammographic screening continuously evolves, and different mammographic screening modalities may result in different perception of density, reflected in different assignment of BI-RADS density categories. Purpose To investigate the effect of screening mammography modality on BI-RADS breast density assessments. Materials and Methods Data were retrospectively analyzed from 24 736 individual women (42.3% [10 455 of 24 736] white women, 57.7% [14 281 of 24 736] black women; mean age, 56.3 years; age range, 40.0-74.9 years) who underwent from one to seven mammographic screening examinations from September 2010 through February 2017 (60 766 examinations). Three screening modalities were used: digital mammography alone (8935 examinations); digital mammography with digital breast tomosynthesis (DBT; 30 779 examinations); and synthetic mammography with DBT (21 052 examinations). Random-effects logistic regression analysis was performed to estimate the likelihood of assignment to high versus low BI-RADS density category according to each modality, adjusted for ethnicity, age, body mass index (BMI), and radiologist. The interactions of modality with ethnicity and BMI on density categorization were also tested with the model. Results Women screened with DBT versus digital mammography alone had lower likelihood regarding categorization of high density breasts (digital mammography and DBT vs digital mammography: odds ratio, 0.69 [95% confidence interval: 0.61, 0.80], P < .001; synthetic mammography and DBT vs digital mammography: odds ratio, 0.43 [95% confidence interval: 0.37, 0.50], P < .001). Lower likelihood of high density was also observed at synthetic mammography and DBT compared with digital mammography and DBT (odds ratio, 0.62; 95% confidence interval: 0.56, 0.69; P < .001). There were interactions of modality with ethnicity (P = .007) and BMI (P = .003) on breast density assessment, with greater differences in density categorization according to modality observed for black women than for white women and groups with higher BMI. Conclusion Breast density categorization may vary by screening mammographic modality, and this effect appears to vary by ethnicity and body mass index. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Philpotts in this issue.

Comparison of performance metrics with digital 2D versus tomosynthesis mammography in the diagnostic setting.

OBJECTIVES: To compare performance metrics between digital 2D mammography (DM) and digital breast tomosynthesis (DBT) in the diagnostic setting. METHODS: Consecutive diagnostic examinations from August 2008 to February 2011 (DM group) and from January 2013 to July 2015 (DM/DBT group) were reviewed. Core biopsy and surgical pathology results within 365 days after the mammogram were collected. Performance metrics, including cancer detection rate (CDR), abnormal interpretation rate (AIR), positive predictive value (PPV) 2, PPV3, sensitivity, and specificity were calculated. Multivariable logistic regression models were fit to compare performance metrics in the DM and DM/DBT groups while adjusting for clinical covariates. RESULTS: A total of 22,883 mammograms were performed before DBT integration (DM group), and 22,824 mammograms were performed after complete DBT integration (DM/DBT group). After adjusting for multiple variables, the CDR was similar in both groups (38.2 per 1,000 examinations in the DM/DBT group versus 31.3 per 1,000 examinations in the DM group, p = 0.14); however, a higher proportion of cancers were invasive rather than in situ in the DM/DBT group [83.7% (731/873) versus 72.3% (518/716), p < 0.01]. The AIR was lower in the DM/DBT group (p < 0.01), and PPV2, PPV3, and specificity were higher in the DM/DBT group (all p = 0.01 or p < 0.01). CONCLUSIONS: Complete integration of DBT into the diagnostic setting is associated with improved diagnostic performance. Increased utilization of DBT may thus result in better patient outcomes and lead to a shift in the benchmarks that have been established for DM. KEY POINTS: • Integration of tomosynthesis into the diagnostic setting is associated with improved performance. • A higher proportion of cancers are invasive rather than in situ with digital breast tomosynthesis. • Increased utilization of tomosynthesis may lead to a shift in established benchmarks.

Uptake of BRCA 1/2 and oncotype DX testing by medical and surgical oncologists.

PURPOSE: The diffusion of genomic testing is critical to the success of precision medicine, but there is limited information on oncologists' uptake of genetic technology. We aimed to assess the frequency with which medical oncologists and surgeons order BRCA 1/2 and Oncotype DX testing for breast cancer patients. METHODS: We surveyed 732 oncologists and surgeons treating breast cancer patients. Physicians were from Florida, New York, New Jersey, and Pennsylvania, and were listed in the 2010 AMA Masterfile or identified by patients. RESULTS: 80.6% of providers ordered BRCA 1/2 testing at least sometimes and 85.4% ordered Oncotype DX (p = 0.01). More frequent ordering of BRCA 1/2 was associated with more positive attitudes toward genetic innovation (OR 1.14, p = 0.001), a belief that testing was likely to be covered by patients' insurance (OR 2.84, p < 0.001), and more frequent ordering of Oncotype DX testing (OR 8.69, p < 0.001). More frequent use of Oncotype DX was associated with a belief that testing was likely to be covered by insurance (OR 7.33, p < 0.001), as well as with more frequent ordering of BRCA 1/2 testing (OR 9.48, p < 0.001). CONCLUSIONS: Nearly one in five providers never or rarely ever ordered BRCA 1/2 testing for their breast cancer patients, and nearly 15% never or rarely ever ordered Oncotype DX. Less frequent ordering of BRCA 1/2 is associated with less frequent use of Oncotype DX testing, and vice versa. Those who do not order BRCA 1/2 testing report less positive attitudes toward genetic innovation. Further education of this subset of providers regarding the benefits of precision medicine may enable more rapid diffusion of genetic technology.

Breast Cancer Characteristics Associated with 2D Digital Mammography versus Digital Breast Tomosynthesis for Screening-detected and Interval Cancers.

Purpose To determine whether the rates and tumor characteristics of screening-detected and interval cancers differ for two-dimensional digital mammography (DM) versus digital breast tomosynthesis (DBT) mammography. Materials and Methods Consecutive screening mammograms from January 2009 to February 2011 (DM group, before DBT integration) and from January 2013 to February 2015 (DBT group, after complete DBT integration) were reviewed. Cancers were considered screening detected if diagnosed within 365 days of a positive screening examination and interval if diagnosed within 365 days of a negative screening examination. Z tests were used to compare cancers on DM versus DBT examinations. Results A total of 948 breast cancers were diagnosed after 78 385 DM and 76 896 DBT examinations. Although the overall rate of screening-detected cancers was similar with DM and DBT (5.0 vs 5.0 per 1000 examinations, P = .98), a higher proportion of screening-detected cancers were invasive rather than in situ with DBT (74.2% [287 of 387] vs 66.0% [260 of 394], P = .01). There were no significant differences in tumor characteristics, including size at pathologic examination, grade, hormone receptor status, and nodal status, between the screening-detected invasive cancers on DM versus DBT (P = .09-.99). The rate of interval cancers was similar with DM and DBT (1.1 vs 1.1 per 1000 examinations, P = .84). Compared with symptomatic interval cancers, magnetic resonance imaging-detected interval cancers were more likely to be minimal cancers. Conclusion The overall rates of screening-detected and interval cancers are similar with DM and DBT, but a higher proportion of screening-detected cancers are invasive rather than in situ with DBT. © RSNA, 2017.

Medical oncologists' willingness to participate in bundled payment programs.

BACKGROUND: Bundled payment programs play an increasingly important role in transforming reimbursement for oncologic care. We assessed determinants of oncologists' willingness to participate in bundled payment programs for breast cancer. We hypothesized that providers would be more likely to participate in bundled payment programs if offered higher levels of reimbursement for each episode of care. METHODS: Oncologists from Florida, New Jersey, New York, and Pennsylvania were identified in the AMA database or by patients listed in state cancer registries. Providers were randomized to receive one of four versions of a survey describing bundled payment programs offering different levels of compensation for the first year of localized breast cancer treatment ($5000, $10,000, $15,000, or $20,000). Physicians rated their likelihood of participation in a bundled program on a Likert scale. Logistic regression was used to analyze determinants of likelihood of participation in bundling. RESULTS: Among 460 respondents, only 17% of oncologists were highly likely to participate in a bundled program paying $5000 for the first year of care, rising to 41% for the $15,000 program, but falling to 34% for the $20,000 program. Likelihood of participation was higher among oncologists who were male, older, and believed that cancer patients should not be offered high-cost drugs with minimal survival benefit. CONCLUSION: Our results suggest that medical oncologists have limited enthusiasm for bundled payments, and higher payments may not overcome resistance to bundling among a substantial proportion of physicians.

BI-RADS Category 3 Comparison: Probably Benign Category after Recall from Screening before and after Implementation of Digital Breast Tomosynthesis.

Purpose To evaluate Breast Imaging Reporting and Data System (BI-RADS) category 3 assessment at diagnostic examination after recall from screening in a large urban population after implementation of digital breast tomosynthesis (DBT) by focusing both on overall use and use stratified by recalled finding type and outcome at 2 years. Materials and Methods This was an intuitional review board-approved and HIPAA-compliant retrospective review of 10 728 digital mammography (DM) examinations from September 1, 2010, to August 30, 2011, and 15 571 screening DBT examinations from October 1, 2011, to February 28, 2013. The recall populations for DM and DBT were 1112 of 10 728 (10.4% of women screened) and 1366 of 15 571 (8.8% of women screened), respectively. Recall examinations were classified according to finding type: calcifications, asymmetry or focal asymmetry, mass, and architectural distortion. Differences between groups were compared by using the χ2 test. Results Although there was no significant change in the utilization rate of BI-RADS category 3 in those patients screened with DM compared with DBT (168 of 10 728, 1.6% for DM vs 206 of 15 571, 1.3% for DBT; P = .102), there was a mean overall reduction of 2.4 women per 1000 (95% confidence interval [CI]: -0.5, 5.4) recommended for short-term follow-up. Lesion types given a BI-RADS category 3 assessment after diagnostic work-up did not change. The distribution of recalled finding types significantly changed with DBT, with increased recall examinations for architectural distortion and mass (P < .001) and decreased recall examinations for asymmetries (P ≤ .001). There was no change in recall examinations for calcifications (P = .977). Conclusion Screening with DBT did not significantly change the utilization rate of BI-RADS category 3 classification; however, the overall number of patients recommended for short-interval follow-up decreased by a mean of 2.4 women per 1000 (95% CI: -0.5, 5.4). © RSNA, 2017 Online supplemental material is available for this article.

Breast cancer screening using tomosynthesis in combination with digital mammography compared to digital mammography alone: a cohort study within the PROSPR consortium.

Digital breast tomosynthesis (DBT) is emerging as the new standard of care for breast cancer screening based on improved cancer detection coupled with reductions in recall compared to screening with digital mammography (DM) alone. However, many prior studies lack follow-up data to assess false negatives examinations. The purpose of this study is to assess if DBT is associated with improved screening outcomes based on follow-up data from tumor registries or pathology. Retrospective analysis of prospective cohort data from three research centers performing DBT screening in the PROSPR consortium from 2011 to 2014 was performed. Recall and biopsy rates were assessed from 198,881 women age 40-74 years undergoing screening (142,883 DM and 55,998 DBT examinations). Cancer, cancer detection, and false negative rates and positive predictive values were assessed on examinations with one year of follow-up. Logistic regression was used to compare DBT to DM adjusting for research center, age, prior breast imaging, and breast density. There was a reduction in recall with DBT compared to DM (8.7 vs. 10.4 %, p < 0.0001), with adjusted OR = 0.68 (95 % CI = 0.65-0.71). DBT demonstrated a statistically significant increase in cancer detection over DM (5.9 vs. 4.4/1000 screened, adjusted OR = 1.45, 95 % CI = 1.12-1.88), an improvement in PPV1 (6.4 % for DBT vs. 4.1 % for DM, adjusted OR = 2.02, 95 % CI = 1.54-2.65), and no significant difference in false negative rates for DBT compared to DM (0.46 vs. 0.60/1000 screened, p = 0.347). Our data support implementation of DBT screening based on increased cancer detection, reduced recall, and no difference in false negative screening examinations.