In a study for which pathologists provided diagnostic interpretation of breast biopsy slides, overall agreement between individual pathologists’ interpretations and those of an expert consensus panel was just 75.3%, according to a study in the March 17 issue of the Journal of the American Medical Association (JAMA).1

The highest level of concordance among the study interpretations was for cases of invasive breast cancer. Lower levels of concordance were observed for cases of ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (atypia).

Approximately 1.6 million women in the United States undergo breast biopsies each year. The accuracy of pathologists’ diagnoses based on these biopsies is an important and inadequately studied area. Nearly a quarter of all breast biopsies indicate with certainty the presence of invasive breast cancer. But for the remainder—the majority of breast biopsies—pathologists categorize the specimens according to a diagnostic spectrum ranging from benign to preinvasive disease.

Breast lesions with DCIS (abnormal breast cells that have not spread outside the duct into the normal surrounding breast tissue) or atypia (a benign lesion of the breast) are associated with significantly higher risks of subsequent invasive carcinoma. Women with these findings may require additional surveillance, prevention, or treatment to reduce their risks.


Joann G. Elmore, MD, MPH, University of Washington.

The reported incidence of DCIS and atypia breast lesions has increased over the past 3 decades, largely as a result of widespread mammography screening. But according to background information provided in the JAMA article, misclassification of such breast lesions may contribute to either overtreatment or undertreatment.

For the study, Joann G. Elmore, MD, MPH, a professor of medicine at the University of Washington, and colleagues examined the extent of diagnostic disagreement among pathologists when compared with a consensus panel reference diagnosis. The study included 115 pathologists who interpret breast biopsies in clinical practices in eight US states.

Between November 2011 and May 2014, participants in the study independently interpreted slides from test sets of 60 breast biopsies (240 total cases, 1 slide per case), including 23 cases of invasive breast cancer, 73 cases of DCIS, 72 cases of atypia, and 72 cases of benign lesions without atypia. Participants were blinded to the interpretations of other study pathologists and the three consensus panel members, who were experienced pathologists internationally recognized for research and continuing medical education on diagnostic breast pathology.

Among the consensus panel members, unanimous agreement of their independent diagnoses was just 75%. However, concordance with the consensus-derived reference diagnoses was 90.3%.

Taking all the cases together, the pathologists who participated in the study provided a total of 6,900 individual interpretations for comparison with the consensus-derived reference diagnoses. Overall, participants’ interpretations agreed with 75% of the consensus panel diagnoses. The concordance rate for cases of invasive breast cancer was 96%. The participants agreed with the consensus-derived reference diagnosis for 87% of cases involving benign lesions without atypia, and for 84% of DCIS cases. However, the concordance rate for cases of atypia was less than half—just 48%.

Overinterpretation of biopsy findings affected roughly a tenth of all cases in the study. Overinterpretation of DCIS as invasive carcinoma was found to have occurred in only 3% of cases. However, overinterpretation of atypia was noted in 17% of cases, and overinterpretation of benign lesions without atypia was noted in 13% of cases.

Underinterpretation of biopsy findings was found to be somewhat more serious, affecting nearly 15% of all cases. Underinterpretation of invasive breast cancer was noted in 4% of cases; underinterpretation of DCIS was noted in 13% of cases; and underinterpretation of atypia was noted in 35% of cases.

Disagreement with the consensus-derived reference diagnosis was significantly more frequent when the biopsies were from women with dense breast tissue, or when they were interpreted by pathologists with lower weekly case volume, those from nonacademic settings, or those from smaller practices. Nevertheless, the absolute number of differences resulting from these factors was generally small.

“The variability of pathology interpretations is relevant to concerns about overdiagnosis of atypia and DCIS. When a biopsy is overinterpreted (e.g., interpreted as DCIS by a pathologist when the consensus-derived reference diagnosis is atypia), a woman may undergo unnecessary surgery, radiation, or hormonal therapy. In addition, overinterpretation of atypia in a biopsy with otherwise benign findings can result in unnecessary heightened surveillance, clinical intervention, costs, and anxiety,” the researchers write. “Given our findings, clinicians and patients may want to obtain a formal second opinion for breast atypia prior to initiating more intensive surveillance or risk reduction using chemoprevention or surgery.”

The authors conclude that further research is needed to understand the relationship of these findings to patient management.


Nancy E. Davidson, MD, University of Pittsburgh.

An accompanying editorial in the issue assesses the significance of the Elmore study.2 “An undesirable short-term outcome from the study by Elmore et al will undoubtedly be heightened anxiety among women who undergo breast biopsy and concern among their physicians about the accuracy of the pathologic diagnosis,” write Nancy E. Davidson, MD, of the University of Pittsburgh Cancer Institute and UPMC Cancer Center, and David L. Rimm, MD, PhD, of the Yale University School of Medicine.

“However, this study confirms that the majority of diagnoses, especially at either end of the spectrum from benign to invasive cancer, are readily and accurately made by practicing pathologists. It also identifies areas of uncertainty that must be addressed, providing a framework for process improvement in the pathology and scientific communities, especially in the diagnosis of atypia. The study supports the value of a second opinion in cases of ambiguity. Indeed, it is axiomatic that an abnormal breast biopsy is certainly a cause for concern but does not constitute a medical emergency. Extra time and care devoted to confirmation of the histologic diagnosis and a thoughtful discussion of the treatment options are imperative.”


David L. Rimm, MD, PhD, Yale University.

“Importantly, breast pathology is a biological continuum from normal to invasive cancer whereas prescription of treatment requires categorization into specific diagnoses,” write the authors. “The goal should be to match emerging biological understanding about breast carcinogenesis with opportunities for tailored treatment in an era of ever more precise, evidence-based medicine.”


  1. Elmore JG, Longton GM, Carney PA, et al. Diagnostic concordance among pathologists interpreting breast biopsy specimens. JAMA. 2015;313(11):1122–1132; doi:10.1001/jama.2015.1405.
  1. Davidson NE, Rimm DL. Expertise vs. evidence in assessment of breast biopsies: an atypical science. JAMA. 2015;313(11):1109–1110; doi:10.1001/jama.2015.1945.