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Following a baseline demographic survey, 87 pathologists interpreted 240 digital whole slide images of breast biopsy specimens representing a range of diagnostic categories from benign to atypia, ductal carcinoma in situ, and invasive cancer. A web-based viewer recorded pathologists’ behaviors while interpreting a subset of 60 randomly selected and randomly ordered slides. To characterize diagnostic search patterns, we used the viewport location, time stamp, and zoom level data to calculate four variables: average zoom level, maximum zoom level, zoom level variance, and scanning percentage. Two distinct search strategies were confirmed: scanning is characterized by panning at a constant zoom level, while drilling involves zooming in and out at various locations. Statistical analysis was applied to examine the associations of different visual interpretive strategies with pathologist characteristics, diagnostic accuracy, and efficiency. We found that females scanned more than males, and age was positively correlated with scanning percentage, while the facility size was negatively correlated. Throughout 60 cases, the scanning percentage and total interpretation time per slide decreased, and these two variables were positively correlated. The scanning percentage was not predictive of diagnostic accuracy. Increasing average zoom level, maximum zoom level, and zoom variance were correlated with over-interpretation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Because of declining participation, the National Health Service Corps' role in improving rural access to primary health care has shifted from placement of scholarship-obligated professionals to recruitment of volunteers and increased emphasis on retention of current providers. Successful care systems include group practices, community-oriented systems, and those committed to continuing professional education. (Author/MSE)

Digital whole slide imaging is an increasingly common medium in pathology, with application to education, telemedicine, and rendering second opinions. It has also made it possible to use eye tracking devices to explore the dynamic visual inspection and interpretation of histopathological features of tissue while pathologists review cases. Using whole slide images, the present study examined how a pathologist's diagnosis is influenced by fixed case-level factors, their prior clinical experience, and their patterns of visual inspection. Participating pathologists interpreted one of two test sets, each containing 12 digital whole slide images of breast biopsy specimens. Cases represented four diagnostic categories as determined via expert consensus: benign without atypia, atypia, ductal carcinoma in situ (DCIS), and invasive cancer. Each case included one or more regions of interest (ROIs) previously determined as of critical diagnostic importance. During pathologist interpretation we tracked eye movements, viewer tool behavior (zooming, panning), and interpretation time. Models were built using logistic and linear regression with generalized estimating equations, testing whether variables at the level of the pathologists, cases, and visual interpretive behavior would independently and/or interactively predict diagnostic accuracy and efficiency. Diagnostic accuracy varied as a function of case consensus diagnosis, replicating earlier research. As would be expected, benign cases tended to elicit false positives, and atypia, DCIS, and invasive cases tended to elicit false negatives. Pathologist experience levels, case consensus diagnosis, case difficulty, eye fixation durations, and the extent to which pathologists' eyes fixated within versus outside of diagnostic ROIs, all independently or interactively predicted diagnostic accuracy. Higher zooming behavior predicted a tendency to over-interpret benign and atypia cases, but not DCIS cases. Efficiency was not predicted by pathologist- or visual search-level variables. Results provide new insights into the medical interpretive process and demonstrate the complex interactions between pathologists and cases that guide diagnostic decision-making. Implications for training, clinical practice, and computer-aided decision aids are considered. [ABSTRACT FROM AUTHOR]

Background. Medical decision making may be influenced by contextual factors. We evaluated whether pathologists are influenced by disease severity of recently observed cases. Methods. Pathologists independently interpreted 60 breast biopsy specimens (one slide per case; 240 total cases in the study) in a prospective randomized observational study. Pathologists interpreted the same cases in 2 phases, separated by a washout period of >6 months. Participants were not informed that the cases were identical in each phase, and the sequence was reordered randomly for each pathologist and between phases. A consensus reference diagnosis was established for each case by 3 experienced breast pathologists. Ordered logit models examined the effect the pathologists’ diagnoses on the preceding case or the 5 preceding cases had on their diagnosis for the subsequent index case. Results. Among 152 pathologists, 49 provided interpretive data in both phases I and II, 66 from only phase I, and 37 from phase II only. In phase I, pathologists were more likely to indicate a more severe diagnosis than the reference diagnosis when the preceding case was diagnosed as ductal carcinoma in situ (DCIS) or invasive cancer (proportional odds ratio [POR], 1.28; 95% confidence interval [CI], 1.15–1.42). Results were similar when considering the preceding 5 cases and for the pathologists in phase II who interpreted the same cases in a different order compared with phase I (POR, 1.17; 95% CI, 1.05–1.31). Conclusion. Physicians appear to be influenced by the severity of previously interpreted test cases. Understanding types and sources of diagnostic bias may lead to improved assessment of accuracy and better patient care. [ABSTRACT FROM AUTHOR]

Background: About half of the United States has legislation requiring radiology facilities to disclose mammographic breast density information to women, often with language recommending discussion of supplemental screening options for women with dense breasts.Objective: To examine variation in breast density assessment across radiologists in clinical practice.Design: Cross-sectional and longitudinal analyses of prospectively collected observational data.Setting: 30 radiology facilities within the 3 breast cancer screening research centers of the Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium.Participants: Radiologists who interpreted at least 500 screening mammograms during 2011 to 2013 (n = 83). Data on 216 783 screening mammograms from 145 123 women aged 40 to 89 years were included.Measurements: Mammographic breast density, as clinically recorded using the 4 Breast Imaging Reporting and Data System categories (heterogeneously dense and extremely dense categories were considered "dense" for analyses), and patient age, race, and body mass index (BMI).Results: Overall, 36.9% of mammograms were rated as showing dense breasts. Across radiologists, this percentage ranged from 6.3% to 84.5% (median, 38.7% [interquartile range, 28.9% to 50.9%]), with multivariable adjustment for patient characteristics having little effect (interquartile range, 29.9% to 50.8%). Examination of patient subgroups revealed that variation in density assessment across radiologists was pervasive in all but the most extreme patient age and BMI combinations. Among women with consecutive mammograms interpreted by different radiologists, 17.2% (5909 of 34 271) had discordant assessments of dense versus nondense status.Limitation: Quantitative measures of mammographic breast density were not available for comparison.Conclusion: There is wide variation in density assessment across radiologists that should be carefully considered by providers and policymakers when considering supplemental screening strategies. The likelihood of a woman being told she has dense breasts varies substantially according to which radiologist interprets her mammogram.Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]

Background: The effect of physician diagnostic variability on accuracy at a population level depends on the prevalence of diagnoses.Objective: To estimate how diagnostic variability affects accuracy from the perspective of a U.S. woman aged 50 to 59 years having a breast biopsy.Design: Applied probability using Bayes' theorem.Setting: B-Path (Breast Pathology) Study comparing pathologists' interpretations of a single biopsy slide versus a reference consensus interpretation from 3 experts.Participants: 115 practicing pathologists (6900 total interpretations from 240 distinct cases).Measurements: A single representative slide from each of the 240 cases was used to estimate the proportion of biopsies with a diagnosis that would be verified if the same slide were interpreted by a reference group of 3 expert pathologists. Probabilities of confirmation (predictive values) were estimated using B-Path Study results and prevalence of biopsy diagnoses for women aged 50 to 59 years in the Breast Cancer Surveillance Consortium.Results: Overall, if 1 representative slide were used per case, 92.3% (95% CI, 91.4% to 93.1%) of breast biopsy diagnoses would be verified by reference consensus diagnoses, with 4.6% (CI, 3.9% to 5.3%) overinterpreted and 3.2% (CI, 2.7% to 3.6%) underinterpreted. Verification of invasive breast cancer and benign without atypia diagnoses is highly probable; estimated predictive values were 97.7% (CI, 96.5% to 98.7%) and 97.1% (CI, 96.7% to 97.4%), respectively. Verification is less probable for atypia (53.6% overinterpreted and 8.6% underinterpreted) and ductal carcinoma in situ (DCIS) (18.5% overinterpreted and 11.8% underinterpreted).Limitations: Estimates are based on a testing situation with 1 slide used per case and without access to second opinions. Population-adjusted estimates may differ for women from other age groups, unscreened women, or women in different practice settings.Conclusion: This analysis, based on interpretation of a single breast biopsy slide per case, predicts a low likelihood that a diagnosis of atypia or DCIS would be verified by a reference consensus diagnosis. This diagnostic grey zone should be considered in clinical management decisions in patients with these diagnoses.Primary Funding Source: National Cancer Institute. [ABSTRACT FROM AUTHOR]

Aim Long non-coding RNAs (lncRNAs) are potential biomarkers for breast cancer risk stratification. LncRNA expression has been investigated primarily by RNA sequencing, quantitative reverse transcription PCR or microarray techniques. In this study, six breast cancerimplicated lncRNAs were investigated by chromogenic in situ hybridisation (CISH). Methods Invasive breast carcinoma (IBC), ductal carcinoma in situ (DCIS) and normal adjacent (NA) breast tissues from 52 patients were screened by CISH. Staining was graded by modified Allred scoring. Results HOTAIR, H19 and KCNQ1OT1 had significantly higher expression levels in IBC and DCIS than NA ( p<0.05), and HOTAIR and H19 were expressed more strongly in IBC than in DCIS tissues (p<0.05). HOTAIR and KCNQ101T were expressed in tumour cells; H19 and MEG3 were expressed in stromal microenvironment cells; MALAT1 was expressed in all cells strongly and ZFAS1 was negative or weakly expressed in all specimens. Conclusion These data corroborate the involvement of three lncRNAs (HOTAIR, H19 and KCNQ1OT1) in breast tumourigenesis and support lncRNA CISH as a potential clinical assay. Importantly, CISH allows identification of the tissue compartment expressing lncRNA. [ABSTRACT FROM AUTHOR]

Objectives: "Assurance behaviors" in medical practice involve providing additional services of marginal or no medical value to avoid adverse outcomes, deter patients from filing malpractice claims, or ensure that legal standards of care were met. The extent to which concerns about medical malpractice influence assurance behaviors of pathologists interpreting breast specimens is unknown.Methods: Breast pathologists (n = 252) enrolled in a nationwide study completed an online survey of attitudes regarding malpractice and perceived alterations in interpretive behavior due to concerns of malpractice. Associations between pathologist characteristics and the impact of malpractice concerns on personal and colleagues' assurance behaviors were determined by χ(2) and logistic regression analysis.Results: Most participants reported using one or more assurance behaviors due to concerns about medical malpractice for both their personal (88%) and colleagues' (88%) practices, including ordering additional stains, recommending additional surgical sampling, obtaining second reviews, or choosing the more severe diagnosis for borderline cases. Nervousness over breast pathology was positively associated with assurance behavior and remained statistically significant in a multivariable logistic regression model (odds ratio, 2.5; 95% confidence interval, 1.0-6.1; P = .043).Conclusions: Practicing US breast pathologists report exercising defensive medicine by using assurance behaviors due to malpractice concerns. [ABSTRACT FROM AUTHOR]

Purpose Margin status is important in guiding decisions to re-excise following breast-conserving surgery (BCS) for breast cancer. The College of American Pathologists (CAP) developed guidelines to standardize pathology reporting; however, compliance with margin documentation guidelines has been shown to vary. The aim of this retrospective study was to determine whether compliance with CAP guidelines affects re-excision and mastectomy rates. Methods We identified 1423 patients diagnosed with breast cancer between 1998 and 2006 who underwent BCS with negative margins. CAP compliance was categorized as maximal, minimal, or non-compliant. Statistical analyses were performed comparing the frequency of re-excision and mastectomy after initial BCS according to CAP margin reporting guideline compliance. Data were adjusted for provider facility by including a clustering variable within the regression model. Results Patients with non-compliant margin reporting were 1.7 times more likely to undergo re-excision and/or mastectomy than those with maximally compliant reporting. Level of compliance was most strongly associated with the frequency of mastectomy; non-compliant margin reporting was associated with a 2.5-fold increase in mastectomy rates compared to maximally compliant reporting. The results did not substantially change when the analyses accounted for clustering at the provider facility level. Conclusions Our findings suggest that compliance with CAP guidelines in pathology reporting may be associated with variation in re-excision and mastectomy rates following BCS. [ABSTRACT FROM AUTHOR]

General frameworks of the cancer screening process are available, but none directly compare the process in detail across different organ sites. This limits the ability of medical and public health professionals to develop and evaluate coordinated screening programs that apply resources and population management strategies available for one cancer site to other sites. We present a trans-organ conceptual model that incorporates a single screening episode for breast, cervical, and colorectal cancers into a unified framework based on clinical guidelines and protocols; the model concepts could be expanded to other organ sites. The model covers four types of care in the screening process: risk assessment, detection, diagnosis, and treatment. Interfaces between different provider teams (eg, primary care and specialty care), including communication and transfer of responsibility, may occur when transitioning between types of care. Our model highlights across each organ site similarities and differences in steps, interfaces, and transitions in the screening process and documents the conclusion of a screening episode. This model was developed within the National Cancer Institute-funded consortium Populationbased Research Optimizing Screening through Personalized Regimens (PROSPR). PROSPR aims to optimize the screening process for breast, cervical, and colorectal cancer and includes seven research centers and a statistical coordinating center. Given current health care reform initiatives in the United States, this conceptual model can facilitate the development of comprehensive quality metrics for cancer screening and promote trans-organ comparative cancer screening research. PROSPR findings will support the design of interventions that improve screening outcomes across multiple cancer sites. [ABSTRACT FROM AUTHOR]