Evaluating Screening Participation, Follow-up, and Outcomes for Breast, Cervical, and Colorectal Cancer in the PROSPR Consortium.

BACKGROUND: Cancer screening is a complex process encompassing risk assessment, the initial screening examination, diagnostic evaluation, and treatment of cancer precursors or early cancers. Metrics that enable comparisons across different screening targets are needed. We present population-based screening metrics for breast, cervical, and colorectal cancers for nine sites participating in the Population-based Research Optimizing Screening through Personalized Regimens consortium. METHODS: We describe how selected metrics map to a trans-organ conceptual model of the screening process. For each cancer type, we calculated calendar year 2013 metrics for the screen-eligible target population (breast: ages 40-74 years; cervical: ages 21-64 years; colorectal: ages 50-75 years). Metrics for screening participation, timely diagnostic evaluation, and diagnosed cancers in the screened and total populations are presented for the total eligible population and stratified by age group and cancer type. RESULTS: The overall screening-eligible populations in 2013 were 305 568 participants for breast, 3 160 128 for cervical, and 2 363 922 for colorectal cancer screening. Being up-to-date for testing was common for all three cancer types: breast (63.5%), cervical (84.6%), and colorectal (77.5%). The percentage of abnormal screens ranged from 10.7% for breast, 4.4% for cervical, and 4.5% for colorectal cancer screening. Abnormal breast screens were followed up diagnostically in almost all (96.8%) cases, and cervical and colorectal were similar (76.2% and 76.3%, respectively). Cancer rates per 1000 screens were 5.66, 0.17, and 1.46 for breast, cervical, and colorectal cancer, respectively. CONCLUSIONS: Comprehensive assessment of metrics by the Population-based Research Optimizing Screening through Personalized Regimens consortium enabled systematic identification of screening process steps in need of improvement. We encourage widespread use of common metrics to allow interventions to be tested across cancer types and health-care settings.

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.

Pathologists' Use of Second Opinions in Interpretation of Melanocytic Cutaneous Lesions: Policies, Practices, and Perceptions.

BACKGROUND: Research examining the role of second opinions in pathology for diagnosis of melanocytic lesions is limited. OBJECTIVE: To assess current laboratory policies, clinical use of second opinions, and pathologists' perceptions of second opinions for melanocytic lesions. MATERIALS AND METHODS: Cross-sectional data collected from 207 pathologists in 10 US states who diagnose melanocytic lesions. The web-based survey ascertained pathologists' professional information, laboratory second opinion policy, use of second opinions, and perceptions of second opinion value for melanocytic lesions. RESULTS: Laboratory policies required second opinions for 31% of pathologists and most commonly required for melanoma in situ (26%) and invasive melanoma (30%). In practice, most pathologists reported requesting second opinions for melanocytic tumors of uncertain malignant potential (85%) and atypical Spitzoid lesions (88%). Most pathologists perceived that second opinions increased interpretive accuracy (78%) and protected them from malpractice lawsuits (62%). CONCLUSION: Use of second opinions in clinical practice is greater than that required by laboratory policies, especially for melanocytic tumors of uncertain malignant potential and atypical Spitzoid lesions. Quality of care in surgical interventions for atypical melanocytic proliferations critically depends on the accuracy of diagnosis in pathology reporting. Future research should examine the extent to which second opinions improve accuracy of melanocytic lesion diagnosis.

Characteristics associated with requests by pathologists for second opinions on breast biopsies.

AIMS: Second opinions in pathology improve patient safety by reducing diagnostic errors, leading to more appropriate clinical treatment decisions. Little objective data are available regarding the factors triggering a request for second opinion despite second opinion consultations being part of the diagnostic system of pathology. Therefore we sought to assess breast biopsy cases and interpreting pathologists characteristics associated with second opinion requests. METHODS: Collected pathologist surveys and their interpretations of 60 test set cases were used to explore the relationships between case characteristics, pathologist characteristics and case perceptions, and requests for second opinions. Data were evaluated by logistic regression and generalised estimating equations. RESULTS: 115 pathologists provided 6900 assessments; pathologists requested second opinions on 70% (4827/6900) of their assessments 36% (1731/4827) of these would not have been required by policy. All associations between case characteristics and requesting second opinions were statistically significant, including diagnostic category, breast density, biopsy type, and number of diagnoses noted per case. Exclusive of institutional policies, pathologists wanted second opinions most frequently for atypia (66%) and least frequently for invasive cancer (20%). Second opinion rates were higher when the pathologist had lower assessment confidence, in cases with higher perceived difficulty, and cases with borderline diagnoses. CONCLUSIONS: Pathologists request second opinions for challenging cases, particularly those with atypia, high breast density, core needle biopsies, or many co-existing diagnoses. Further studies should evaluate whether the case characteristics identified in this study could be used as clinical criteria to prompt system-level strategies for mandating second opinions.

The diagnostic challenge of low-grade ductal carcinoma in situ.

BACKGROUND: Diagnostic agreement among pathologists is 84% for ductal carcinoma in situ (DCIS). Studies of interpretive variation according to grade are limited. METHODS: A national sample of 115 pathologists interpreted 240 breast pathology test set cases in the Breast Pathology Study and their interpretations were compared to expert consensus interpretations. We assessed agreement of pathologists' interpretations with a consensus reference diagnosis of DCIS dichotomised into low- and high-grade lesions. Generalised estimating equations were used in logistic regression models of rates of under- and over-interpretation of DCIS by grade. RESULTS: We evaluated 2097 independent interpretations of DCIS (512 low-grade DCIS and 1585 high-grade DCIS). Agreement with reference diagnoses was 46% (95% confidence interval [CI] 42-51) for low-grade DCIS and 83% (95% CI 81-86) for high-grade DCIS. The proportion of reference low-grade DCIS interpretations over-interpreted by pathologists (i.e. categorised as either high-grade DCIS or invasive cancer) was 23% (95% CI 19-28); 30% (95% CI 26-34) were interpreted as a lower diagnostic category (atypia or benign proliferative). Reference high-grade DCIS was under-interpreted in 14% (95% CI 12-16) of observations and only over-interpreted 3% (95% CI 2-4). CONCLUSION: Grade is a major factor when examining pathologists' variability in diagnosing DCIS, with much lower agreement for low-grade DCIS cases compared to high-grade. These findings support the hypothesis that low-grade DCIS poses a greater interpretive challenge than high-grade DCIS, which should be considered when developing DCIS management strategies.

A Randomized Study Comparing Digital Imaging to Traditional Glass Slide Microscopy for Breast Biopsy and Cancer Diagnosis.

BACKGROUND: Digital whole slide imaging may be useful for obtaining second opinions and is used in many countries. However, the U.S. Food and Drug Administration requires verification studies. METHODS: Pathologists were randomized to interpret one of four sets of breast biopsy cases during two phases, separated by ≥9 months, using glass slides or digital format (sixty cases per set, one slide per case, n = 240 cases). Accuracy was assessed by comparing interpretations to a consensus reference standard. Intraobserver reproducibility was assessed by comparing the agreement of interpretations on the same cases between two phases. Estimated probabilities of confirmation by a reference panel (i.e., predictive values) were obtained by incorporating data on the population prevalence of diagnoses. RESULTS: Sixty-five percent of responding pathologists were eligible, and 252 consented to randomization; 208 completed Phase I (115 glass, 93 digital); and 172 completed Phase II (86 glass, 86 digital). Accuracy was slightly higher using glass compared to digital format and varied by category: invasive carcinoma, 96% versus 93% (P = 0.04); ductal carcinoma in situ (DCIS), 84% versus 79% (P < 0.01); atypia, 48% versus 43% (P = 0.08); and benign without atypia, 87% versus 82% (P < 0.01). There was a small decrease in intraobserver agreement when the format changed compared to when glass slides were used in both phases (P = 0.08). Predictive values for confirmation by a reference panel using glass versus digital were: invasive carcinoma, 98% and 97% (not significant [NS]); DCIS, 70% and 57% (P = 0.007); atypia, 38% and 28% (P = 0.002); and benign without atypia, 97% and 96% (NS). CONCLUSIONS: In this large randomized study, digital format interpretations were similar to glass slide interpretations of benign and invasive cancer cases. However, cases in the middle of the spectrum, where more inherent variability exists, may be more problematic in digital format. Future studies evaluating the effect these findings exert on clinical practice and patient outcomes are required.

Diagnostic Reproducibility: What Happens When the Same Pathologist Interprets the Same Breast Biopsy Specimen at Two Points in Time?

BACKGROUND: Surgeons may receive a different diagnosis when a breast biopsy is interpreted by a second pathologist. The extent to which diagnostic agreement by the same pathologist varies at two time points is unknown. METHODS: Pathologists from eight U.S. states independently interpreted 60 breast specimens, one glass slide per case, on two occasions separated by ≥9 months. Reproducibility was assessed by comparing interpretations between the two time points; associations between reproducibility (intraobserver agreement rates); and characteristics of pathologists and cases were determined and also compared with interobserver agreement of baseline interpretations. RESULTS: Sixty-five percent of invited, responding pathologists were eligible and consented; 49 interpreted glass slides in both study phases, resulting in 2940 interpretations. Intraobserver agreement rates between the two phases were 92% [95% confidence interval (CI) 88-95] for invasive breast cancer, 84% (95% CI 81-87) for ductal carcinoma-in-situ, 53% (95% CI 47-59) for atypia, and 84% (95% CI 81-86) for benign without atypia. When comparing all study participants' case interpretations at baseline, interobserver agreement rates were 89% (95% CI 84-92) for invasive cancer, 79% (95% CI 76-81) for ductal carcinoma-in-situ, 43% (95% CI 41-45) for atypia, and 77% (95% CI 74-79) for benign without atypia. CONCLUSIONS: Interpretive agreement between two time points by the same individual pathologist was low for atypia and was similar to observed rates of agreement for atypia between different pathologists. Physicians and patients should be aware of the diagnostic challenges associated with a breast biopsy diagnosis of atypia when considering treatment and surveillance decisions.

Radiologists' interpretive skills in screening vs. diagnostic mammography: are they related?

PURPOSE: This study aims to determine whether radiologists who perform well in screening also perform well in interpreting diagnostic mammography. MATERIALS AND METHODS: We evaluated the accuracy of 468 radiologists interpreting 2,234,947 screening and 196,164 diagnostic mammograms. Adjusting for site, radiologist, and patient characteristics, we identified radiologists with performance in the highest tertile and compared to those with lower performance. RESULTS: A moderate correlation was noted for radiologists' accuracy when interpreting screening versus their accuracy on diagnostic examinations: sensitivity (rspearman=0.51, 95% CI: 0.22, 0.80; P=.0006) and specificity (rspearman=0.40, 95% CI: 0.30, 0.49; P<.0001). CONCLUSION: Different educational approaches to screening and diagnostic imaging should be considered.

Achieving consensus for the histopathologic diagnosis of melanocytic lesions: use of the modified Delphi method.

OBJECTIVE: To understand the sophisticated nature of coming to consensus when diagnosing complex melanocytic lesions among a panel of experienced dermatopathologists. METHODS: A total of 240 melanocytic lesions were assessed independently by three experienced dermatopathologists with their diagnoses mapped into one of five Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-DX) categories: (I) nevus/mild atypia, (II) moderate atypia, (III) severe atypia/melanoma in situ, (IV) T1a invasive melanoma and (V) ≥ T1b invasive melanoma. The dermatopathologists then discussed the cases, using a modified Delphi method to facilitated consensus building for cases with discordant diagnoses. RESULTS: For most cases, a majority of interpretations (two or three of three) agreed with the consensus diagnosis in 95% of Category I, 64% of Category II, 84% of Category III, 88% for Category IV and 100% of Category V cases. Disagreements were typically due to diagnostic threshold differences (64.5%), differing contents on slides even though the slides were sequential cuts (18.5%), and missed findings (15.3%). Disagreements were resolved via discussion of histopathologic features and their significance while reviewing the slides using a multi-headed microscope, considering treatment recommendations, citing existing literature, reviewing additional slides for a case, and choosing a provisional/borderline diagnosis to capture diverse opinions. All experienced pathologists participating in this study reported that the process of coming to consensus was challenging for borderline cases and may have represented compromise rather than consensus. They also reported the process changed their approaches to diagnosing complex melanocytic lesions. CONCLUSIONS: The most frequent reason for disagreement of experienced dermatopathologists was differences in diagnostic thresholds related to observer viewpoints. A range of approaches was needed to come to consensus, and this may guide pathology groups who do not currently hold consensus conferences.

Ages at menarche- and menopause-related genetic variants in relation to terminal duct lobular unit involution in normal breast tissue.

Reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have been associated with higher breast cancer risk. Younger age at menarche and older age at menopause have been previously related to lower levels of TDLU involution. To determine a possible genetic link, we examined whether single-nucleotide polymorphisms (SNPs) previously established in genome-wide association studies (GWAS) for ages at menarche and menopause are associated with TDLU involution. We conducted a pooled analysis of 862 women from two studies. H&E tissue sections were assessed for numbers of TDLUs and acini/TDLU. Poisson regression models were used to estimate associations of 36 menarche- and 21 menopause-SNPs with TDLU counts, acini counts/TDLU, and the product of these two measures, adjusting for age and study site. Fourteen percent of evaluated SNPs (eight SNPs) were associated with TDLU counts at p < 0.05, suggesting an enrichment of associations with TDLU counts. However, only menopause-SNPs had >50 % that were either significantly or nonsignificantly associated with TDLU measures in the directions consistent with their relationships shown in GWAS. Among ten SNPs that were statistically significantly associated with at least one TDLU involution measure (p < 0.05), seven SNPs (rs466639: RXRG; rs2243803: SLC14A2; rs2292573: GAB2; rs6438424: 3q13.32; rs7606918: METAP1D; rs11668344: TMEM150B; rs1635501: EXO1) were associated in the consistent directions. Our data suggest that the loci associated with ages at menarche and menopause may influence TDLU involution, suggesting some shared genetic mechanisms. However, larger studies are needed to confirm the results.

Relation of Serum Estrogen Metabolites with Terminal Duct Lobular Unit Involution Among Women Undergoing Diagnostic Image-Guided Breast Biopsy.

Higher levels of circulating estrogens and estrogen metabolites (EMs) have been associated with higher breast cancer risk. In breast tissues, reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have also been linked to elevated breast cancer risk. However, it is unknown whether reduced TDLU involution mediates the risk associated with circulating EMs. In a cross-sectional analysis of 94 premenopausal and 92 postmenopausal women referred for clinical breast biopsy at an academic facility in Vermont, we examined the associations of 15 EMs, quantified using liquid chromatography-tandem mass spectrometry, with the number of TDLUs and acini count/TDLU using zero-inflated Poisson regression with a robust variance estimator and ordinal logistic regression models, respectively. All analyses were stratified by menopausal status and adjusted for potential confounders. Among premenopausal women, comparing the highest vs. the lowest tertiles, levels of unconjugated estradiol (risk ratio (RR) = 1.74, 95 % confidence interval (CI) = 1.06-2.87, p trend = 0.03), 2-hydroxyestrone (RR = 1.74, 95 % CI = 1.01-3.01, p trend = 0.04), and 4-hydroxyestrone (RR = 1.74, 95 % CI = 0.99-3.06, p trend = 0.04) were associated with significantly higher TDLU count. Among postmenopausal women, higher levels of estradiol (RR = 2.09, 95 % CI = 1.01-4.30, p trend = 0.04) and 16α-hydroxyestrone (RR = 2.27, 95 % CI = 1.29-3.99, p trend = 0.02) were significantly associated with higher TDLU count. Among postmenopausal women, higher levels of EMs, specifically conjugated estrone and 2- and 4-pathway catechols, were also associated with higher acini count/TDLU. Our data suggest that higher levels of serum EMs are generally associated with lower levels of TDLU involution.

Follow-Up of Abnormal Breast and Colorectal Cancer Screening by Race/Ethnicity.

INTRODUCTION: Timely follow-up of abnormal tests is critical to the effectiveness of cancer screening, but may vary by screening test, healthcare system, and sociodemographic group. METHODS: Timely follow-up of abnormal mammogram and fecal occult blood testing or fecal immunochemical tests (FOBT/FIT) were compared by race/ethnicity using Population-Based Research Optimizing Screening through Personalized Regimens consortium data. Participants were women with an abnormal mammogram (aged 40-75 years) or FOBT/FIT (aged 50-75 years) in 2010-2012. Analyses were performed in 2015. Timely follow-up was defined as colonoscopy ≤3 months following positive FOBT/FIT; additional imaging or biopsy ≤3 months following Breast Imaging Reporting and Data System Category 0, 4, or 5 mammograms; or ≤9 months following Category 3 mammograms. Logistic regression was used to model receipt of timely follow-up adjusting for study site, age, year, insurance, and income. RESULTS: Among 166,602 mammograms, 10.7% were abnormal; among 566,781 FOBT/FITs, 4.3% were abnormal. Nearly 96% of patients with abnormal mammograms received timely follow-up versus 68% with abnormal FOBT/FIT. There was greater variability in receipt of follow-up across healthcare systems for positive FOBT/FIT than for abnormal mammograms. For mammography, black women were less likely than whites to receive timely follow-up (91.8% vs 96.0%, OR=0.71, 95% CI=0.51, 0.97). For FOBT/FIT, Hispanics were more likely than whites to receive timely follow-up than whites (70.0% vs 67.6%, OR=1.12, 95% CI=1.04, 1.21). CONCLUSIONS: Timely follow-up among women was more likely for abnormal mammograms than FOBT/FITs, with small variations in follow-up rates by race/ethnicity and larger variation across healthcare systems.

Identifying and processing the gap between perceived and actual agreement in breast pathology interpretation.

We examined how pathologists' process their perceptions of how their interpretations on diagnoses for breast pathology cases agree with a reference standard. To accomplish this, we created an individualized self-directed continuing medical education program that showed pathologists interpreting breast specimens how their interpretations on a test set compared with a reference diagnosis developed by a consensus panel of experienced breast pathologists. After interpreting a test set of 60 cases, 92 participating pathologists were asked to estimate how their interpretations compared with the standard for benign without atypia, atypia, ductal carcinoma in situ and invasive cancer. We then asked pathologists their thoughts about learning about differences in their perceptions compared with actual agreement. Overall, participants tended to overestimate their agreement with the reference standard, with a mean difference of 5.5% (75.9% actual agreement; 81.4% estimated agreement), especially for atypia and were least likely to overestimate it for invasive breast cancer. Non-academic affiliated pathologists were more likely to more closely estimate their performance relative to academic affiliated pathologists (77.6 vs 48%; P=0.001), whereas participants affiliated with an academic medical center were more likely to underestimate agreement with their diagnoses compared with non-academic affiliated pathologists (40 vs 6%). Before the continuing medical education program, nearly 55% (54.9%) of participants could not estimate whether they would overinterpret the cases or underinterpret them relative to the reference diagnosis. Nearly 80% (79.8%) reported learning new information from this individualized web-based continuing medical education program, and 23.9% of pathologists identified strategies they would change their practice to improve. In conclusion, when evaluating breast pathology specimens, pathologists do a good job of estimating their diagnostic agreement with a reference standard, but for atypia cases, pathologists tend to overestimate diagnostic agreement. Many participants were able to identify ways to improve.

Use of Digital Whole Slide Imaging in Dermatopathology.

Digital whole slide imaging (WSI) is an emerging technology for pathology interpretation, with specific challenges for dermatopathology, yet little is known about pathologists' practice patterns or perceptions regarding WSI for interpretation of melanocytic lesions. A national sample of pathologists (N = 207) was recruited from 864 invited pathologists from ten US states (CA, CT, HI, IA, KY, LA, NJ, NM, UT, and WA). Pathologists who had interpreted melanocytic lesions in the past year were surveyed in this cross-sectional study. The survey included questions on pathologists' experience, WSI practice patterns and perceptions using a 6-point Likert scale. Agreement was summarized with descriptive statistics to characterize pathologists' use and perceptions of WSI. The majority of participating pathologists were between 40 and 59 years of age (62%) and not affiliated with an academic medical center (71%). Use of WSI was seen more often among dermatopathologists and participants affiliated with an academic medical center. Experience with WSI was reported by 41%, with the most common type of use being for education and testing (CME, board exams, and teaching in general, 71%), and clinical use at tumor boards and conferences (44%). Most respondents (77%) agreed that accurate diagnoses can be made with this technology, and 59% agreed that benefits of WSI outweigh concerns. However, 78% of pathologists reported that digital slides are too slow for routine clinical interpretation. The respondents were equally split as to whether they would like to adopt WSI (49%) or not (51%). The majority of pathologists who interpret melanocytic lesions do not use WSI, but among pathologists who do, use is largely for CME, licensure/board exams, and teaching. Positive perceptions regarding WSI slightly outweigh negative perceptions. Understanding practice patterns with WSI as dissemination advances may facilitate concordance of perceptions with adoption of the technology.

How concerns and experiences with medical malpractice affect dermatopathologists' perceptions of their diagnostic practices when interpreting cutaneous melanocytic lesions.

OBJECTIVE: We sought to identify characteristics associated with past malpractice lawsuits and how malpractice concerns may affect interpretive practices. METHODS: We surveyed 207 of 301 (68.8%) eligible dermatopathologists who interpret melanocytic skin lesions in 10 states. The survey assessed dermatopathologists' demographic and clinical practice characteristics, perceptions of how medical malpractice concerns could influence their interpretive practices, and past malpractice lawsuits. RESULTS: Of dermatopathologists, 33% reported past malpractice experiences. Factors associated with being sued included older age (57 vs 48 years, P < .001), lack of board certification or fellowship training in dermatopathology (76.5% vs 53.2%, P = .001), and greater number of years interpreting melanocytic lesions (>20 years: 52.9% vs 20.1%, P < .001). Of participants, 64% reported being moderately or extremely confident in their melanocytic interpretations. Although most dermatopathologists believed that malpractice concerns increased their likelihood of ordering specialized pathology tests, obtaining recuts, and seeking a second opinion, none of these practices were associated with past malpractice. Most dermatopathologists reported concerns about potential harms to patients that may result from their assessments of melanocytic lesions. LIMITATIONS: Limitations of this study include lack of validation of and details about the malpractice suits experienced by participating dermatopathologists. In addition, the study assessed perceptions of practice rather than actual practices that might be associated with malpractice incidents. CONCLUSIONS: Most dermatopathologists reported apprehension about how malpractice affects their clinical practice and are concerned about patient safety irrespective of whether they had actually experienced a medical malpractice suit.

Facility Mammography Volume in Relation to Breast Cancer Screening Outcomes.

OBJECTIVES: To clarify the relationship between facility-level mammography interpretive volume and breast cancer screening outcomes. METHODS: We calculated annual mammography interpretive volumes from 2000-2009 for 116 facilities participating in the U.S. Breast Cancer Surveillance Consortium (BCSC). Radiology, pathology, cancer registry, and women's self-report information were used to determine the indication for each exam, cancer characteristics, and patient characteristics. We examined the effect of annual total volume and percentage of mammograms that were screening on cancer detection rates using multinomial logistic regression adjusting for age, race/ethnicity, time since last mammogram, and BCSC registries. "Good prognosis" tumours were defined as screen-detected invasive cancers that were <15 mm, early stage, and lymph node negative at diagnosis. RESULTS: From 3,098,481 screening mammograms, 9,899 cancers were screen-detected within one year of the exam. Approximately 80% of facilities had annual total interpretive volumes of >2,000 mammograms, and 42% had >5,000. Higher total volume facilities were significantly more likely to diagnose invasive tumours with good prognoses (odds ratio [OR] 1.32; 95% confidence interval [CI] 1.10-1.60, for total volume of 5,000-10,000/year v. 1,000-2,000/year; p-for-trend <0.001). A concomitant decrease in tumours with poor prognosis was seen (OR 0.78; 95%CI 0.63-0.98 for total volume of 5,000-10,000/year v. 1,000-2,000/year). CONCLUSIONS: Mammography facilities with higher total interpretive volumes detected more good prognosis invasive tumours and fewer poor prognosis invasive tumours, suggesting that women attending these facilities may be more likely to benefit from screening.

Diagnostic concordance among pathologists interpreting breast biopsy specimens.

IMPORTANCE: A breast pathology diagnosis provides the basis for clinical treatment and management decisions; however, its accuracy is inadequately understood. OBJECTIVES: To quantify the magnitude of diagnostic disagreement among pathologists compared with a consensus panel reference diagnosis and to evaluate associated patient and pathologist characteristics. DESIGN, SETTING, AND PARTICIPANTS: Study of pathologists who interpret breast biopsies in clinical practices in 8 US states. EXPOSURES: Participants independently interpreted slides between November 2011 and May 2014 from test sets of 60 breast biopsies (240 total cases, 1 slide per case), including 23 cases of invasive breast cancer, 73 ductal carcinoma in situ (DCIS), 72 with atypical hyperplasia (atypia), and 72 benign cases without atypia. Participants were blinded to the interpretations of other study pathologists and consensus panel members. Among the 3 consensus panel members, unanimous agreement of their independent diagnoses was 75%, and concordance with the consensus-derived reference diagnoses was 90.3%. MAIN OUTCOMES AND MEASURES: The proportions of diagnoses overinterpreted and underinterpreted relative to the consensus-derived reference diagnoses were assessed. RESULTS: Sixty-five percent of invited, responding pathologists were eligible and consented to participate. Of these, 91% (N = 115) completed the study, providing 6900 individual case diagnoses. Compared with the consensus-derived reference diagnosis, the overall concordance rate of diagnostic interpretations of participating pathologists was 75.3% (95% CI, 73.4%-77.0%; 5194 of 6900 interpretations). Among invasive carcinoma cases (663 interpretations), 96% (95% CI, 94%-97%) were concordant, and 4% (95% CI, 3%-6%) were underinterpreted; among DCIS cases (2097 interpretations), 84% (95% CI, 82%-86%) were concordant, 3% (95% CI, 2%-4%) were overinterpreted, and 13% (95% CI, 12%-15%) were underinterpreted; among atypia cases (2070 interpretations), 48% (95% CI, 44%-52%) were concordant, 17% (95% CI, 15%-21%) were overinterpreted, and 35% (95% CI, 31%-39%) were underinterpreted; and among benign cases without atypia (2070 interpretations), 87% (95% CI, 85%-89%) were concordant and 13% (95% CI, 11%-15%) were overinterpreted. Disagreement with the reference diagnosis was statistically significantly higher among biopsies from women with higher (n = 122) vs lower (n = 118) breast density on prior mammograms (overall concordance rate, 73% [95% CI, 71%-75%] for higher vs 77% [95% CI, 75%-80%] for lower, P < .001), and among pathologists who interpreted lower weekly case volumes (P < .001) or worked in smaller practices (P = .034) or nonacademic settings (P = .007). CONCLUSIONS AND RELEVANCE: In this study of pathologists, in which diagnostic interpretation was based on a single breast biopsy slide, overall agreement between the individual pathologists' interpretations and the expert consensus-derived reference diagnoses was 75.3%, with the highest level of concordance for invasive carcinoma and lower levels of concordance for DCIS and atypia. Further research is needed to understand the relationship of these findings with patient management.

Relationship of serum estrogens and metabolites with area and volume mammographic densities.

Elevated mammographic density is a breast cancer risk factor, which has a suggestive, but unproven, relationship with increased exposure to sex steroid hormones. We examined associations of serum estrogens and estrogen metabolites with area and novel volume mammographic density measures among 187 women, ages 40-65, undergoing diagnostic breast biopsies at an academic facility in Vermont. Serum parent estrogens, estrone and estradiol, and their 2-, 4-, and 16-hydroxylated metabolites were measured using liquid chromatography-tandem mass spectrometry. Area mammographic density was measured in the breast contralateral to the biopsy using thresholding software; volume mammographic density was quantified using a density phantom. Linear regression was used to estimate associations of estrogens with mammographic densities, adjusted for age and body mass index, and stratified by menopausal status and menstrual cycle phase. Weak, positive associations between estrogens, estrogen metabolites, and mammographic density were observed, primarily among postmenopausal women. Among premenopausal luteal phase women, the 16-pathway metabolite estriol was associated with percent area (p = 0.04) and volume (p = 0.05) mammographic densities and absolute area (p = 0.02) and volume (p = 0.05) densities. Among postmenopausal women, levels of total estrogens, the sum of parent estrogens, and 2-, 4- and 16-hydroxylation pathway metabolites were positively associated with area density measures (percent: p = 0.03, p = 0.04, p = 0.01, p = 0.02, p = 0.07; absolute: p = 0.02, p = 0.02, p = 0.01, p = 0.02, p = 0.03, respectively) but not volume density measures. Our data suggest that serum estrogen profiles are weak determinants of mammographic density and that analysis of different density metrics may provide complementary information about relationships of estrogen exposure to breast tissue composition.

Demographic and practice characteristics of pathologists who enjoy breast tissue interpretation.

Physician attributes, job satisfaction and confidence in clinical skills are associated with enhanced performance and better patient outcomes. We surveyed 252 pathologists to evaluate associations between enjoyment of breast pathology, demographic/clinical characteristics and diagnostic performance. Diagnostic performance was determined by comparing pathologist assessments of a set of 60 cases with consensus assessments of the same cases made by a panel of experienced pathologists. Eighty-three percent of study participants reported enjoying breast pathology. Pathologists who enjoy breast interpretation were more likely to review ≥10 cases/week (p = 0.003), report breast interpretation expertise (p = 0.013) and have high levels of confidence interpreting breast pathology (p < 0.001). These pathologists were less likely to report that the field was challenging (p < 0.001) and that breast cases make them more nervous than other types of pathology (p < 0.001). Enjoyment was not associated with diagnostic performance. Millions of women undergo breast biopsy annually, thus it is reassuring that although nearly a fifth of practicing pathologists who interpret breast tissue report not enjoying the field, precision is not impacted.

Trends in breast biopsy pathology diagnoses among women undergoing mammography in the United States: a report from the Breast Cancer Surveillance Consortium.

BACKGROUND: Current data on the pathologic diagnoses of breast biopsy after mammography can inform patients, clinicians, and researchers about important population trends. METHODS: Breast Cancer Surveillance Consortium data on 4,020,140 mammograms between 1996 and 2008 were linked to 76,567 pathology specimens. Trends in diagnoses in biopsies by time and risk factors (patient age, breast density, and family history of breast cancer) were examined for screening and diagnostic mammography (performed for a breast symptom or short-interval follow-up). RESULTS: Of the total mammograms, 88.5% were screening and 11.5% diagnostic; 1.2% of screening and 6.8% of diagnostic mammograms were followed by biopsies. The frequency of biopsies over time was stable after screening mammograms, but increased after diagnostic mammograms. For biopsies obtained after screening, frequencies of invasive carcinoma increased over time for women ages 40-49 and 60-69, Ductal carcinoma in situ (DCIS) increased for those ages 40-69, whereas benign diagnoses decreased for all ages. No trends in pathology diagnoses were found following diagnostic mammograms. Dense breast tissue was associated with high-risk lesions and DCIS relative to nondense breast tissue. Family history of breast cancer was associated with DCIS and invasive cancer. CONCLUSIONS: Although the frequency of breast biopsy after screening mammography has not changed over time, the percentages of biopsies with DCIS and invasive cancer diagnoses have increased. Among biopsies following mammography, women with dense breasts or family history of breast cancer were more likely to have high-risk lesions or invasive cancer. These findings are relevant to breast cancer screening and diagnostic practices.