Relationship of Serum Progesterone and Progesterone Metabolites with Mammographic Breast Density and Terminal Ductal Lobular Unit Involution among Women Undergoing Diagnostic Breast Biopsy.

The association of progesterone/progesterone metabolites with elevated mammographic breast density (MBD) and delayed age-related terminal duct lobular unit (TDLU) involution, strong breast cancer risk factors, has received limited attention. Using a reliable liquid chromatography-tandem mass-spectrometry assay, we quantified serum progesterone/progesterone metabolites and explored cross-sectional relationships with MBD and TDLU involution among women, ages 40-65, undergoing diagnostic breast biopsy. Quantitative MBD measures were estimated in pre-biopsy digital mammograms.

Relationship of circulating insulin-like growth factor-I and binding proteins 1-7 with mammographic density among women undergoing image-guided diagnostic breast biopsy.

Background: Mammographic density (MD) is a strong breast cancer risk factor that reflects fibroglandular and adipose tissue composition, but its biologic underpinnings are poorly understood. Insulin-like growth factor binding proteins (IGFBPs) are markers that may be associated with MD given their hypothesized role in breast carcinogenesis. IGFBPs sequester IGF-I, limiting its bioavailability.

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.

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.

Communication Practices of Mammography Facilities and Timely Follow-up of a Screening Mammogram with a BI-RADS 0 Assessment.

Rationale And Objectives: The objective of this study was to evaluate the association of communication practices with timely follow-up of screening mammograms read as Breast Imaging Reporting and Data Systems (BI-RADS) 0 in the Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium.

Materials And Methods: A radiology facility survey was conducted in 2015 with responses linked to screening mammograms obtained in 2011-2014. We considered timely follow-up to be within 15 days of the screening mammogram.

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.

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.

Correlation Between Screening Mammography Interpretive Performance on a Test Set and Performance in Clinical Practice.

Rationale And Objectives: Evidence is inconsistent about whether radiologists' interpretive performance on a screening mammography test set reflects their performance in clinical practice. This study aimed to estimate the correlation between test set and clinical performance and determine if the correlation is influenced by cancer prevalence or lesion difficulty in the test set.

Materials And Methods: This institutional review board-approved study randomized 83 radiologists from six Breast Cancer Surveillance Consortium registries to assess one of four test sets of 109 screening mammograms each; 48 radiologists completed a fifth test set of 110 mammograms 2 years later.

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.

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.

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.

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.

Association between breast cancer genetic susceptibility variants and terminal duct lobular unit involution of the breast.

Terminal duct lobular units (TDLUs) are the predominant source of future breast cancers, and lack of TDLU involution (higher TDLU counts, higher acini count per TDLU and the product of the two) is a breast cancer risk factor. Numerous breast cancer susceptibility single nucleotide polymorphisms (SNPs) have been identified, but whether they are associated with TDLU involution is unknown. In a pooled analysis of 872 women from two studies, we investigated 62 established breast cancer SNPs and relationships with TDLU involution.

Radiologist Agreement for Mammographic Recall by Case Difficulty and Finding Type.

Purpose: The aim of this study was to assess agreement of mammographic interpretations by community radiologists with consensus interpretations of an expert radiology panel to inform approaches that improve mammographic performance.

Methods: From 6 mammographic registries, 119 community-based radiologists were recruited to assess 1 of 4 randomly assigned test sets of 109 screening mammograms with comparison studies for no recall or recall, giving the most significant finding type (mass, calcifications, asymmetric density, or architectural distortion) and location. The mean proportion of agreement with an expert radiology panel was calculated by cancer status, finding type, and difficulty level of identifying the finding at the patient, breast, and lesion level.

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.

Relationships between mammographic density, tissue microvessel density, and breast biopsy diagnosis.

Background: Women with high levels of mammographic density (MD) have a four- to six-fold increased risk of developing breast cancer; however, most neither have a prevalent tumor nor will they develop one. Magnetic resonance imaging (MRI) studies suggest that background parenchymal enhancement, an indicator of vascularity, is related to increased breast cancer risk. Correlations of microvessel density (MVD) in tissue, MD and biopsy diagnosis have not been defined, and we investigated these relationships among 218 women referred for biopsy.

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.

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.

Evaluation of 12 strategies for obtaining second opinions to improve interpretation of breast histopathology: simulation study.

Objective:  To evaluate the potential effect of second opinions on improving the accuracy of diagnostic interpretation of breast histopathology.

Design:  Simulation study.

Setting:  12 different strategies for acquiring independent second opinions.

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.

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.

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.

Variability in Pathologists' Interpretations of Individual Breast Biopsy Slides: A Population Perspective.

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.

Circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3 and terminal duct lobular unit involution of the breast: a cross-sectional study of women with benign breast disease.

Background: Terminal duct lobular units (TDLUs) are the primary structures from which breast cancers and their precursors arise. Decreased age-related TDLU involution and elevated mammographic density are both correlated and independently associated with increased breast cancer risk, suggesting that these characteristics of breast parenchyma might be linked to a common factor. Given data suggesting that increased circulating levels of insulin-like growth factors (IGFs) factors are related to reduced TDLU involution and increased mammographic density, we assessed these relationships using validated quantitative methods in a cross-sectional study of women with benign breast disease.