Ductal Carcinoma In Situ Biology, Biomarkers, and Diagnosis

Abstract

Ductal carcinoma in situ (DCIS) is an often-diagnosed breast disease and a known, non-obligate, precursor to invasive breast carcinoma. In this review, we explore the clinical and pathological features of DCIS, fundamental elements of DCIS biology including gene expression and genetic events, the relationship of DCIS with recurrence and invasive breast cancer, and the interaction of DCIS with the microenvironment. We also survey how these various elements are being used to solve the clinical conundrum of how to optimally treat a disease that has potential to progress, and yet is also likely over-treated in a significant proportion of cases.

Dichotomous histopathological assessment of ductal carcinomain situof the breast results in substantial interobserver concordance

“…19 Data are considered to be unreliable when KA is <0.667. With 0.800 > KA ≥ 0.667, it is (2), non-solid ductal carcinoma in situ (DCIS) growth pattern versus solid DCIS growth pattern (3), presence or absence of intraductal calcifications (4), no necrosis versus any necrosis (5), no or single-cell necrosis versus focal or extensive necrosis (6), non-extensive necrosis versus extensive necrosis (7), absence or presence of apocrine differentiation (8), <1% periductal myxoid stroma versus ≥1% periductal myxoid stroma (9), <33% periductal myxoid stroma versus ≥33% periductal myxoid stroma (10), <66% periductal myxoid stroma versus ≥66% periductal myxoid stroma (11), no stromal inflammation versus any stromal inflammation (12), no or mild stromal inflammation versus moderate or extensive stromal inflammation (13), and non-extensive stromal inflammation versus extensive stromal inflammation (14). [Colour figure can be viewed at wileyonlinelibrary.com] advised to draw only tentative conclusions.…”

“…Ongoing clinical trials such as the COMET, LORD and LORIS trials, which are investigating watchful waiting strategies for low‐grade DCIS, might provide crucial information to fill this gap in our knowledge . The main motive for such trials is the increasing awareness that significant numbers of DCIS patients are currently overtreated, as not all DCIS cases will become invasive …”

“…Ideally, adequate prognostic markers should enable us to reduce the number of patients who undergo surgery, as well as the number of patients who receive adjuvant irradiation and hormonal therapy. The current uncertainty about what constitutes ‘high‐risk DCIS’ causes significant variability in treatment . In the past, several histopathological and immunohistochemical characteristics of DCIS have been investigated, often with conflicting results regarding their potential for recurrence risk prediction.…”

“…[2][3][4] The main motive for such trials is the increasing awareness that significant numbers of DCIS patients are currently overtreated, as not all DCIS cases will become invasive. 1,5 If these trials can prove that watchful waiting is not inferior to standard surgical treatment in a selected subgroup of patients, the search for proper prognostic markers is likely to be intensified. If DCIS is left untreated, adequate prognosticators are necessary to estimate the risk of upstaging of DCIS to invasive cancer on the initial biopsy, and to evaluate the risk of evolution towards invasion in the future.…”

“…The current uncertainty about what constitutes 'high-risk DCIS' causes significant variability in treatment. 5 In the past, several histopathological and immunohistochemical characteristics of DCIS have been investigated, often with conflicting results regarding their potential for recurrence risk prediction. We wondered whether interobserver variability might explain such conflicting results.…”