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.

Multispectral Imaging of Metabolic Fluorophores: Comparing In Vivo and Fresh Ex Vivo Tissue.

The enhanced uptake of glucose by cancer cells via aerobic glycolysis occurs when the lactic acid pathway is favored over the citric acid cycle. The lactic acid cycle in cancer cells influences the cytosolic concentration of metabolic fluorophores including NADH (the reduced form of nicotinamide adenine dinucleotide) and flavin adenine dinucleotide (FAD). In particular, the literature has shown that breast cancer influences the relative magnitude of fluorescence from NADH and FAD. A multispectral imaging system has been developed for rapid non-destructive imaging of intrinsic fluorescence in tissue. This paper compares in vivo data to fresh ex vivo data gathered as a function of time in mouse models. The data indicate that, if measured within 30 min of excision, a cancer diagnosis in fresh ex vivo tissue correlates with a cancer diagnosis in in vivo tissue. These results justify a plan to evaluate fresh ex vivo human tissue to quantify the sensitivity and specificity of the multispectral system.

Breast Cancer-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual.

Answer questions and earn CME/CNE The revision of the eighth edition of the primary tumor, lymph node, and metastasis (TNM) classification of the American Joint Commission of Cancer (AJCC) for breast cancer was determined by a multidisciplinary team of breast cancer experts. The panel recognized the need to incorporate biologic factors, such as tumor grade, proliferation rate, estrogen and progesterone receptor expression, human epidermal growth factor 2 (HER2) expression, and gene expression prognostic panels into the staging system. AJCC levels of evidence and guidelines for all tumor types were followed as much as possible. The panel felt that, to maintain worldwide value, the tumor staging system should remain based on TNM anatomic factors. However, the recognition of the prognostic influence of grade, hormone receptor expression, and HER2 amplification mandated their inclusion into the staging system. The value of commercially available, gene-based assays was acknowledged and prognostic input added. Tumor biomarkers and low Oncotype DX recurrence scores can alter prognosis and stage. These updates are expected to provide additional precision and flexibility to the staging system and were based on the extent of published information and analysis of large, as yet unpublished databases. The eighth edition of the AJCC TNM staging system, thus, provides a flexible platform for prognostic classification based on traditional anatomic factors, which can be modified and enhanced using patient biomarkers and multifactorial prognostic panel data. The eighth edition remains the worldwide basis for breast cancer staging and will incorporate future online updates to remain timely and relevant. CA Cancer J Clin 2017;67:290-303. © 2017 American Cancer Society.

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.

From Image to Diagnosis: Characterizing Sources of Error in Histopathologic Interpretation.

An accurate histopathologic diagnosis on surgical biopsy material is necessary for the clinical management of patients and has important implications for research, clinical trial design/enrollment, and public health education. This study used a mixed methods approach to isolate sources of diagnostic error while residents and attending pathologists interpreted digitized breast biopsy slides. Ninety participants, including pathology residents and attending physicians at major United States medical centers reviewed a set of 14 digitized whole-slide images of breast biopsies. Each case had a consensus-defined diagnosis and critical region of interest (cROI) representing the most significant pathology on the slide. Participants were asked to view unmarked digitized slides, draw their participant region of interest (pROI), describe its features, and render a diagnosis. Participants' review behavior was tracked using case viewer software and an eye-tracking device. Diagnostic accuracy was calculated in comparison to the consensus diagnosis. We measured the frequency of errors emerging during 4 interpretive phases: (1) detecting the cROI, (2) recognizing its relevance, (3) using the correct terminology to describe findings in the pROI, and (4) making a diagnostic decision. According to eye-tracking data, trainees and attending pathologists were very likely (∼94% of the time) to find the cROI when inspecting a slide. However, trainees were less likely to consider the cROI relevant to their diagnosis. Pathology trainees (41% of cases) were more likely to use incorrect terminology to describe pROI features than attending pathologists (21% of cases). Failure to accurately describe features was the only factor strongly associated with an incorrect diagnosis. Identifying where errors emerge in the interpretive and/or descriptive process and working on building organ-specific feature recognition and verbal fluency in describing those features are critical steps for achieving competency in diagnostic decision making.

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.

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.

Mammary collagen architecture and its association with mammographic density and lesion severity among women undergoing image-guided breast biopsy.

BACKGROUND: Elevated mammographic breast density is a strong breast cancer risk factor with poorly understood etiology. Increased deposition of collagen, one of the main fibrous proteins present in breast stroma, has been associated with increased mammographic density. Collagen fiber architecture has been linked to poor outcomes in breast cancer. However, relationships of quantitative collagen fiber features assessed in diagnostic biopsies with mammographic density and lesion severity are not well-established. METHODS: Clinically indicated breast biopsies from 65 in situ or invasive breast cancer cases and 73 frequency matched-controls with a benign biopsy result were used to measure collagen fiber features (length, straightness, width, alignment, orientation and density (fibers/µm2)) using second harmonic generation microscopy in up to three regions of interest (ROIs) per biopsy: normal, benign breast disease, and cancer. Local and global mammographic density volumes were quantified in the ipsilateral breast in pre-biopsy full-field digital mammograms. Associations of fibrillar collagen features with mammographic density and severity of biopsy diagnosis were evaluated using generalized estimating equation models with an independent correlation structure to account for multiple ROIs within each biopsy section. RESULTS: Collagen fiber density was positively associated with the proportion of stroma on the biopsy slide (p < 0.001) and with local percent mammographic density volume at both the biopsy target (p = 0.035) and within a 2 mm perilesional ring (p = 0.02), but not with global mammographic density measures. As severity of the breast biopsy diagnosis increased at the ROI level, collagen fibers tended to be less dense, shorter, straighter, thinner, and more aligned with one another (p < 0.05). CONCLUSIONS: Collagen fiber density was positively associated with local, but not global, mammographic density, suggesting that collagen microarchitecture may not translate into macroscopic mammographic features. However, collagen fiber features may be markers of cancer risk and/or progression among women referred for biopsy based on abnormal breast imaging.

Identifying key barriers to effective breast cancer control in rural settings.

Breast cancer is the most common cancer and the second most common cause of cancer mortality among women in the United States. Efforts to promote breast cancer control in rural settings face specific challenges. Access to breast cancer screening, diagnosis, and treatment services is impaired by shortages of primary care and specialist providers, and geographic distance from medical facilities. Women in rural areas have comparable breast cancer mortality rates compared to women in urban settings, but this is due in large part to lower incidence rates and masks a substantial rural/urban disparity in breast cancer survival among women diagnosed with breast cancer. Mammography screening utilization rates are slightly lower among rural women than their urban counterparts, with a corresponding increase in late stage breast cancer. Differences in breast cancer survival persist after controlling for stage at diagnosis, largely due to disparities in access to treatment. Travel distance to treatment centers is the most substantial barrier to improved breast cancer outcomes in rural areas. While numerous interventions have been demonstrated in controlled studies to be effective in promoting treatment access and adherence, widespread dissemination in public health and clinical practice remains lacking. Efforts to improve breast cancer control in rural areas should focus on implementation strategies for improving access to breast cancer treatments.

More scanning, but not zooming, is associated with diagnostic accuracy in evaluating digital breast pathology slides.

Diagnoses of medical images can invite strikingly diverse strategies for image navigation and visual search. In computed tomography screening for lung nodules, distinct strategies, termed scanning and drilling, relate to both radiologists' clinical experience and accuracy in lesion detection. Here, we examined associations between search patterns and accuracy for pathologists (N = 92) interpreting a diverse set of breast biopsy images. While changes in depth in volumetric images reveal new structures through movement in the z-plane, in digital pathology changes in depth are associated with increased magnification. Thus, "drilling" in radiology may be more appropriately termed "zooming" in pathology. We monitored eye-movements and navigation through digital pathology slides to derive metrics of how quickly the pathologists moved through XY (scanning) and Z (zooming) space. Prior research on eye-movements in depth has categorized clinicians as either "scanners" or "drillers." In contrast, we found that there was no reliable association between a clinician's tendency to scan or zoom while examining digital pathology slides. Thus, in the current work we treated scanning and zooming as continuous predictors rather than categorizing as either a "scanner" or "zoomer." In contrast to prior work in volumetric chest images, we found significant associations between accuracy and scanning rate but not zooming rate. These findings suggest fundamental differences in the relative value of information types and review behaviors across two image formats. Our data suggest that pathologists gather critical information by scanning on a given plane of depth, whereas radiologists drill through depth to interrogate critical features.

Modeling the natural history of ductal carcinoma in situ based on population data.

BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) has increased substantially since the introduction of mammography screening. Nevertheless, little is known about the natural history of preclinical DCIS in the absence of biopsy or complete excision. METHODS: Two well-established population models evaluated six possible DCIS natural history submodels. The submodels assumed 30%, 50%, or 80% of breast lesions progress from undetectable DCIS to preclinical screen-detectable DCIS; each model additionally allowed or prohibited DCIS regression. Preclinical screen-detectable DCIS could also progress to clinical DCIS or invasive breast cancer (IBC). Applying US population screening dissemination patterns, the models projected age-specific DCIS and IBC incidence that were compared to Surveillance, Epidemiology, and End Results data. Models estimated mean sojourn time (MST) in the preclinical screen-detectable DCIS state, overdiagnosis, and the risk of progression from preclinical screen-detectable DCIS. RESULTS: Without biopsy and surgical excision, the majority of DCIS (64-100%) in the preclinical screen-detectable state progressed to IBC in submodels assuming no DCIS regression (36-100% in submodels allowing for DCIS regression). DCIS overdiagnosis differed substantially between models and submodels, 3.1-65.8%. IBC overdiagnosis ranged 1.3-2.4%. Submodels assuming DCIS regression resulted in a higher DCIS overdiagnosis than submodels without DCIS regression. MST for progressive DCIS varied between 0.2 and 2.5 years. CONCLUSIONS: Our findings suggest that the majority of screen-detectable but unbiopsied preclinical DCIS lesions progress to IBC and that the MST is relatively short. Nevertheless, due to the heterogeneity of DCIS, more research is needed to understand the progression of DCIS by grades and molecular subtypes.

Multicenter Evaluation of Breast Cancer Screening with Digital Breast Tomosynthesis in Combination with Synthetic versus Digital Mammography.

BackgroundDigital breast tomosynthesis (DBT) combined with digital mammography (DM) is increasingly used in the United States instead of DM alone for breast cancer screening. Early screening outcomes incorporating synthetic mammography (SM) with DBT have suggested that SM is an acceptable non-radiation dose alternative to DM.PurposeTo compare multicenter outcomes from breast cancer screening with SM/DBT versus DM/DBT.Materials and MethodsThis was a retrospective study of consecutive screening mammograms obtained at two institutions. Eligible studies consisted of 34 106 DM/DBT examinations between October 3, 2011, and October 31, 2014, and 34 180 SM/DBT examinations between January 7, 2015, and February 2, 2018, at the University of Pennsylvania and 51 148 DM/DBT examinations between January 1, 2012, and May 31, 2016, and 31 929 SM/DBT examinations between June 1, 2016, and March 30, 2018, at the University of Vermont. Demographics of women who attended screening and results from screening were recorded. Recall rate, biopsy rate, false-negative rate, cancer detection rate, positive predictive value, sensitivity, and specificity were calculated according to modality and institution. Descriptive statistics, χ2 tests, and logistic regression were used in analysis.ResultsThe study included 151 363 screening examinations among 151 363 women (mean age, 58.1 years ± 10.9 [standard deviation]). The unadjusted recall rate was lower with SM/DBT than with DM/DBT (7.0% [4630 of 66 109 examinations] for SM/DBT vs 7.9% [6742 of 85 254 examinations] for DM/DBT; P < .01). However, after multivariable adjustment, SM/DBT was associated with a slightly higher recall rate compared with DM/DBT (adjusted odds ratio [OR], 1.06; adjusted 95% CI: 1.01, 1.11; P = .02). Similarly, after multivariable adjustment, SM/DBT was associated with slightly lower specificity compared with DM/DBT (adjusted OR, 0.95; adjusted 95% CI: 0.90, 0.99; P = .02). There was no statistically significant difference in biopsy rate (P = .54), false-negative rate (P = .38), cancer detection rate (P = .55), invasive or in situ cancer detection rate (P = .52 and P = .98, respectively), positive predictive value (P = .78), or sensitivity (P = .33) for SM/DBT versus DM/DBT overall or within either institution (P > .05 for all).ConclusionBreast cancer screening performance is maintained within benchmarks when synthetic mammography replaces digital mammography in digital breast tomosynthesis imaging.© RSNA, 2020Online supplemental material is available for this article.See also the editorial by Lång in this issue.

Strategies for expanding colorectal cancer screening at community health centers.

Community health centers are uniquely positioned to address disparities in colorectal cancer (CRC) screening as they have addressed other disparities. In 2012, the federal Health Resources and Services Administration, which is the funding agency for the health center program, added a requirement that health centers report CRC screening rates as a standard performance measure. These annually reported, publically available data are a major strategic opportunity to improve screening rates for CRC. The Patient Protection and Affordable Care Act enacted provisions to expand the capacity of the federal health center program. The recent report of the Institute of Medicine on integrating public health and primary care included an entire section devoted to CRC screening as a target for joint work. These developments make this the ideal time to integrate lifesaving CRC screening into the preventive care already offered by health centers. This article offers 5 strategies that address the challenges health centers face in increasing CRC screening rates. The first 2 strategies focus on improving the processes of primary care. The third emphasizes working productively with other medical providers and institutions. The fourth strategy is about aligning leadership. The final strategy is focused on using tools that have been derived from models that work.

Strategies for expanding colorectal cancer screening at community health centers.

Community health centers are uniquely positioned to address disparities in colorectal cancer (CRC) screening as they have addressed other disparities. In 2012, the federal Health Resources and Services Administration, which is the funding agency for the health center program, added a requirement that health centers report CRC screening rates as a standard performance measure. These annually reported, publically available data are a major strategic opportunity to improve screening rates for CRC. The Patient Protection and Affordable Care Act enacted provisions to expand the capacity of the federal health center program. The recent report of the Institute of Medicine on integrating public health and primary care included an entire section devoted to CRC screening as a target for joint work. These developments make this the ideal time to integrate lifesaving CRC screening into the preventive care already offered by health centers. This article offers 5 strategies that address the challenges health centers face in increasing CRC screening rates. The first 2 strategies focus on improving the processes of primary care. The third emphasizes working productively with other medical providers and institutions. The fourth strategy is about aligning leadership. The final strategy is focused on using tools that have been derived from models that work. CA Cancer J Clin 2013. © 2013 American Cancer Society, Inc.

Real-time detection of breast cancer at the cellular level.

Novel optoelectronic instrumentation has been developed for the multispectral imaging of autofluorescence emitted by metabolic fluorophores. The images resolve individual cells while spectra are collected for each pixel in the images. These datacubes are generated at a rate of 10 per second-fast enough for surgical guidance. The data is processed in real time to provide a single color-coded image to the surgeon. To date, the system has been applied to fresh, ex vivo, human surgical specimens and has distinguished breast cancer from benign tissue. The approach is applicable to in vivo measurements of surgical margins and needle-based optical biopsies. Ongoing work demonstrates that the system has great potential for translation to a hand-held probe with high sensitivity and specificity.

Time-varying risks of second events following a DCIS diagnosis in the population-based Vermont DCIS cohort.

PURPOSE: Long-term disease-free survival patterns following surgical, radiation, and endocrine therapy treatments for ductal carcinoma in situ (DCIS) are not well characterized in general US practice. METHODS: We identified 1252 women diagnosed with DCIS in Vermont during 1994-2012 using data from the Vermont Breast Cancer Surveillance System, a statewide registry of breast imaging and pathology records. Poisson regression and Cox regression with time-varying hazards were used to evaluate disease-free survival among self-selected treatment groups. RESULTS: With 7.8 years median follow-up, 192 cases experienced a second breast cancer diagnosis. For women treated with breast-conserving surgery (BCS) alone, the annual rate of second events decreased from 3.1% (95% CI 2.2-4.2%) during follow-up years 1-5 to 1.7% (95% CI 0.7-3.5%) after 10 years. In contrast, the annual rate of second events among women treated with BCS plus adjuvant radiation therapy increased from 1.8% (95% CI 1.1-2.6%) during years 1-5 to 2.8% (95% CI 1.6-4.7%) after 10 years (P < 0.05 for difference in trend compared to BCS alone). Annual rates of second events also increased over time among women treated with BCS plus adjuvant radiation and endocrine therapy (P = 0.01 for difference in trend compared to BCS alone). The rate of contralateral events increased after 10 years for all groups with adjuvant treatments. The rate of second events did not vary over time among women who underwent ipsilateral mastectomy (P = 0.62). CONCLUSIONS: Long-term risk of a second event after DCIS varies over time in a manner dependent on initial treatment.

Detection Rates for Benign and Malignant Diagnoses on Breast Cancer Screening With Digital Breast Tomosynthesis in a Statewide Mammography Registry Study.

OBJECTIVE: The objective of our study was to determine whether detection rates of specific benign and malignant diagnoses differ for breast cancer screening with digital breast tomosynthesis (DBT) versus full-field digital mammography (FFDM) alone. MATERIALS AND METHODS: We analyzed observational data from the Vermont Breast Cancer Surveillance System, including 86,349 DBT screening examinations and 97,378 FFDM screening examinations performed at eight radiology facilities in Vermont that adopted DBT screening during 2012-2016. We determined the most severe diagnosis made within 6 months after positive screening examinations. Multivariable-adjusted logistic regression was used to compare detection rates for specific diagnoses on DBT versus FFDM. RESULTS: Compared with FFDM, DBT had a lower recall rate (adjusted odds ratio [OR], 0.81; 95% CI, 0.77-0.85) but comparable biopsy rate (OR = 1.05; 95% CI, 0.93-1.17), benign biopsy rate (OR = 1.12; 95% CI, 0.97-1.29), and cancer detection rate (OR = 0.94; 95% CI, 0.78-1.14). Among benign diagnoses, DBT and FFDM had comparable detection rates for nonproliferative lesions (OR = 1.19; 95% CI, 0.92-1.53), fibroepithelial proliferations (OR = 1.24; 95% CI, 0.85-1.81), proliferative lesions without atypia (OR = 1.13; 95% CI, 0.90-1.42), atypical lesions (OR = 0.77; 95% CI, 0.43-1.38), and lobular carcinoma in situ (LCIS) (OR = 0.92; 95% CI, 0.53-1.61). Among malignant diagnoses, DBT and FFDM had comparable detection rates for ductal carcinoma in situ (OR = 1.05; 95% CI, 0.70-1.57) and invasive breast cancer (OR = 0.92; 95% CI, 0.74-1.13), with no statistically significant differences in detection of invasive ductal carcinoma (OR = 0.83; 95% CI, 0.66-1.06), invasive lobular carcinoma (OR = 1.11; 95% CI, 0.59-2.07), or invasive mixed ductal-lobular carcinoma (OR = 1.49; 95% CI, 0.65-3.39). CONCLUSION: Compared with FFDM, breast cancer screening with DBT has a lower recall rate while detecting a similar distribution of benign and malignant diagnoses.

Second opinion strategies in breast pathology: a decision analysis addressing over-treatment, under-treatment, and care costs.

PURPOSE: To estimate the potential near-term population impact of alternative second opinion breast biopsy pathology interpretation strategies. METHODS: Decision analysis examining 12-month outcomes of breast biopsy for nine breast pathology interpretation strategies in the U.S. health system. Diagnoses of 115 practicing pathologists in the Breast Pathology Study were compared to reference-standard-consensus diagnoses with and without second opinions. Interpretation strategies were defined by whether a second opinion was sought universally or selectively (e.g., 2nd opinion if invasive). Main outcomes were the expected proportion of concordant breast biopsy diagnoses, the proportion involving over- or under-interpretation, and cost of care in U.S. dollars within one-year of biopsy. RESULTS: Without a second opinion, 92.2% of biopsies received a concordant diagnosis. Concordance rates increased under all second opinion strategies, and the rate was highest (95.1%) and under-treatment lowest (2.6%) when all biopsies had second opinions. However, over-treatment was lowest when second opinions were sought selectively for initial diagnoses of invasive cancer, DCIS, or atypia (1.8 vs. 4.7% with no 2nd opinions). This strategy also had the lowest projected 12-month care costs ($5.907 billion vs. $6.049 billion with no 2nd opinions). CONCLUSIONS: Second opinion strategies could lower overall care costs while reducing both over- and under-treatment. The most accurate cost-saving strategy required second opinions for initial diagnoses of invasive cancer, DCIS, or atypia.

Comparative effectiveness of incorporating a hypothetical DCIS prognostic marker into breast cancer screening.

PURPOSE: Due to limitations in the ability to identify non-progressive disease, ductal carcinoma in situ (DCIS) is usually managed similarly to localized invasive breast cancer. We used simulation modeling to evaluate the potential impact of a hypothetical test that identifies non-progressive DCIS. METHODS: A discrete-event model simulated a cohort of U.S. women undergoing digital screening mammography. All women diagnosed with DCIS underwent the hypothetical DCIS prognostic test. Women with test results indicating progressive DCIS received standard breast cancer treatment and a decrement to quality of life corresponding to the treatment. If the DCIS test indicated non-progressive DCIS, no treatment was received and women continued routine annual surveillance mammography. A range of test performance characteristics and prevalence of non-progressive disease were simulated. Analysis compared discounted quality-adjusted life years (QALYs) and costs for test scenarios to base-case scenarios without the test. RESULTS: Compared to the base case, a perfect prognostic test resulted in a 40% decrease in treatment costs, from $13,321 to $8005 USD per DCIS case. A perfect test produced 0.04 additional QALYs (16 days) for women diagnosed with DCIS, added to the base case of 5.88 QALYs per DCIS case. The results were sensitive to the performance characteristics of the prognostic test, the proportion of DCIS cases that were non-progressive in the model, and the frequency of mammography screening in the population. CONCLUSION: A prognostic test that identifies non-progressive DCIS would substantially reduce treatment costs but result in only modest improvements in quality of life when averaged over all DCIS cases.

Using deep convolutional neural networks to identify and classify tumor-associated stroma in diagnostic breast biopsies.

The breast stromal microenvironment is a pivotal factor in breast cancer development, growth and metastases. Although pathologists often detect morphologic changes in stroma by light microscopy, visual classification of such changes is subjective and non-quantitative, limiting its diagnostic utility. To gain insights into stromal changes associated with breast cancer, we applied automated machine learning techniques to digital images of 2387 hematoxylin and eosin stained tissue sections of benign and malignant image-guided breast biopsies performed to investigate mammographic abnormalities among 882 patients, ages 40-65 years, that were enrolled in the Breast Radiology Evaluation and Study of Tissues (BREAST) Stamp Project. Using deep convolutional neural networks, we trained an algorithm to discriminate between stroma surrounding invasive cancer and stroma from benign biopsies. In test sets (928 whole-slide images from 330 patients), this algorithm could distinguish biopsies diagnosed as invasive cancer from benign biopsies solely based on the stromal characteristics (area under the receiver operator characteristics curve = 0.962). Furthermore, without being trained specifically using ductal carcinoma in situ as an outcome, the algorithm detected tumor-associated stroma in greater amounts and at larger distances from grade 3 versus grade 1 ductal carcinoma in situ. Collectively, these results suggest that algorithms based on deep convolutional neural networks that evaluate only stroma may prove useful to classify breast biopsies and aid in understanding and evaluating the biology of breast lesions.