A pathologist's assessment is considered the """"""""gold standard"""""""" for deciding whether cancer is present or absent and whether atypical epithelium is reported. However, extensive variation between pathologists has been documented, with disagreement in the diagnosis of atypical ductal hyperplasia (ADH) in more than 50% of cases and a misclassification rate for cases designated by experts as ductal carcinoma in situ (DCIS) of 17%. We propose to evaluate the extent of variability, its sources and its impact on women undergoing breast biopsy. Our research will also evaluate possible techniques to improve accuracy, such as double reading. To accomplish our study aims we will develop four diagnostic test sets, weighted to include a high percentage of cases with ADH and DCIS, as defined by a panel of international experts. More than 100 pathologists from multiple regions of the U.S. will independently review the same test sets during two phases, separated by 6 months.
Our specific aims are: 1. To assess the accuracy of pathologists in the interpretation of breast pathology specimens and quantify the extent and possible sources of intra- and inter-observer variability. 2. To assess whether the addition of independent double reading by two pathologists on all or a subset of cases can improve the accuracy of interpretation of breast pathology specimens. 3. To quantify the implications of variability among pathologists'interpretations of breast specimens on short-term patient care and associated resource utilization within the U.S. population. We hypothesize that the following characteristics are associated with lower accuracy: a) Patient characteristics (age <50 years, African American, dense breast, extensive background proliferative change, ADH and DCIS interpretation): and b) Pathologist characteristics (e.g., less clinical experience). In summary, we will evaluate the accuracy of breast pathology interpretation, emphasizing the classification of ADH and DCIS, where previous studies reveal a concerning degree of diagnostic errors. This large multi- center study of community pathologists addresses a topic that has growing clinical importance. Our research team includes international experts in breast pathology, statistical measurement of test accuracy, and studies of observer variability in clinical medicine, as well as an advisory committee of clinical experts in breast disease. The proposed work is innovative in that we will go beyond simply quantifying the existence of errors. We will study patient and physician characteristics associated with inaccurate diagnoses. We will then evaluate methods for improving health care delivery using double reading. Finally, we will use a systematic method to make projections from our data to clinical implications of inaccurate diagnoses.

Public Health Relevance

Surprisingly little research has investigated the accuracy of pathologists in diagnosing cancer, yet the pathologists'assessment is the gold standard for deciding whether cancer is present or absent and, in the case of breast tissue, whether atypical cells are noted. We propose a series of studies to evaluate the extent and impact of variability in breast pathology interpretation. We will also evaluate the impact of double reading on overall accuracy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA140560-04
Application #
8268509
Study Section
Health Services Organization and Delivery Study Section (HSOD)
Program Officer
Marcus, Pamela M
Project Start
2009-07-07
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
4
Fiscal Year
2012
Total Cost
$646,440
Indirect Cost
$106,399
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Mercan, Caner; Aksoy, Selim; Mercan, Ezgi et al. (2018) Multi-Instance Multi-Label Learning for Multi-Class Classification of Whole Slide Breast Histopathology Images. IEEE Trans Med Imaging 37:316-325
Carney, Patricia A; Frederick, Paul D; Reisch, Lisa M et al. (2018) Complexities of perceived and actual performance in pathology interpretation: A comparison of cutaneous melanocytic skin and breast interpretations. J Cutan Pathol 45:478-490
BrunyƩ, Tad T; Mercan, Ezgi; Weaver, Donald L et al. (2017) Accuracy is in the eyes of the pathologist: The visual interpretive process and diagnostic accuracy with digital whole slide images. J Biomed Inform 66:171-179
Geller, Berta M; Nelson, Heidi D; Weaver, Donald L et al. (2017) Characteristics associated with requests by pathologists for second opinions on breast biopsies. J Clin Pathol 70:947-953
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Samples, Laura S; Rendi, Mara H; Frederick, Paul D et al. (2017) Surgical implications and variability in the use of the flat epithelial atypia diagnosis on breast biopsy specimens. Breast 34:34-43
Jackson, Sara L; Frederick, Paul D; Pepe, Margaret S et al. (2017) Diagnostic Reproducibility: What Happens When the Same Pathologist Interprets the Same Breast Biopsy Specimen at Two Points in Time? Ann Surg Oncol 24:1234-1241
Frederick, Paul D; Nelson, Heidi D; Carney, Patricia A et al. (2017) The Influence of Disease Severity of Preceding Clinical Cases on Pathologists' Medical Decision Making. Med Decis Making 37:91-100
Allison, Kimberly H; Rendi, Mara H; Peacock, Sue et al. (2016) Histological features associated with diagnostic agreement in atypical ductal hyperplasia of the breast: illustrative cases from the B-Path study. Histopathology 69:1028-1046

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