Stromal characteristics are adequate prognosticators for recurrence risk in ductal carcinoma in situ of the breast

Abstract

Background: Ductal carcinoma in situ (DCIS) of the breast constitutes a heterogeneous group of nonobligate precursors for invasive breast cancer. To date, adequate risk stratification is lacking, which is presumed to result in overtreatment. We previously identified myxoid stromal architecture as a potential prognosticator for loco-regional recurrence. In the present study, we investigated the prognostic potential of stromal characteristics. Methods: Hematoxylin and eosin stained slides from 211 DCIS patients were reviewed. The following histological features were dichotomously assessed: nuclear grade, DCIS architecture, presence of necrosis, intraductal calcifications, stromal inflammation and myxoid stromal architecture. Loco-regional recurrences constituted the primary endpoint. Results: Cox regression analysis showed that high nuclear grade, myxoid stromal architecture and moderate to extensive stromal inflammation were significantly associated with decreased recurrence-free survival, independent of radiotherapy. Based on these features, a combined risk score (CRS) was calculated, ranging from zero to three. A high CRS of three was associated with significantly shorter recurrence-free survival. Nineteen patients had a CRS of three, of which three relapsed (15.7%), whereas only one out of 113 patients with a CRS of zero relapsed (0.9%). Conclusions: We were able to validate our previously reported findings regarding the prognostic potential of myxoid periductal stroma in an independent DCIS patient cohort. A CRS based on nuclear grade, myxoid stromal architecture and stromal inflammation might facilitate discrimination of low risk from high risk patients. Consequently, the CRS may tailor adjuvant therapy. Future research should investigate whether radiotherapy can be safely omitted in patients with a low CRS.

Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast: the DCISion study

“…The presence and extent of chronic inflammatory infiltrates in the periductal stroma (regardless of its architecture) was recorded in a semi-quantitative manner as previously described and was preferentially assessed at low magnification, distant from the biopsy site (if present). 18,24,25,27 Low stromal inflammation was defined as periductal stroma that is not infiltrated by lymphocytes, or that was infiltrated by few loosely arranged lymphocytes with apparent intervening stroma. 27 High stromal inflammation was defined as periductal stroma containing a chronic inflammatory infiltrate that consists of at least one lymphoid aggregate (i.e.…”

A retrospective alternative for active surveillance trials for ductal carcinoma in situ of the breast

“…It would therefore be interesting to investigate the prognostic value of two‐tier grading as nonhigh grade vs . high grade instead of a three‐tier grading system . This two‐tier morphological grading is corroborated by several molecular and gene expression studies that indicate a low‐grade and high‐grade pathway in breast cancer development .…”

“…45,46 It would therefore be interesting to investigate the prognostic value of two-tier grading as nonhigh grade vs. high grade instead of a three-tier grading system. 47 This two-tier morphological grading is corroborated by several molecular and gene expression studies that indicate a low-grade and high-grade pathway in breast cancer development. [48][49][50] The identification of alternative robust prognostic markers besides nuclear grade is of utmost importance, because it is likely that overtreatment of DCIS patients will continue despite the potential usage of active surveillance strategies in this limited subpopulation of "low-risk" DCIS.…”

Novel methodology to image stromal tissue and assess its morphological features with polarized light: towards a tumour microenvironment prognostic signature

“…For example, fibres aligned perpendicular to the tumour, termed TACS-3, are thought to facilitate a path for metastasis and have been shown to inversely correlate with disease-free survival [8]. In addition, higher fibrillar stroma content in peritumoural environment has been shown to be associated with worse disease-free survival in breast cancer [8,13]. Pancreatic ductal adenocarcinoma patients with high peri-tumoural stroma density have been shown to have better outcomes than those with intermediate or low stroma density [26].…”

“…In breast cancer, it has been observed that more mammographic dense breast tissues, containing more extensive connective tissue are associated with worse outcomes [8]. Further, it has been suggested that the amount of peri-tumoural stroma in breast cancer, quantified via tumour-to-stroma ratio, correlates with risk of local recurrence, distant metastasis, and patient survival [8][9][10][11][12][13].…”