Original contributionCan tumor-associated macrophages in ductal carcinoma in situ on biopsy predict invasive carcinoma on excision?☆
Introduction
The diagnosis of ductal carcinoma in situ (DCIS) of the breast increased significantly in recent decades with the introduction and routine use of mammographic screening in women. National Comprehensive Cancer Network guidelines recommend treatment of DCIS with complete excision with or without adjuvant radiation. Because of the indolent behavior of most cases of DCIS, recent trials have explored active surveillance of DCIS diagnosed on core biopsy, without complete excision. Unfortunately, core biopsy has been reported to underestimate the presence of a synchronous invasive breast cancer in up to 47% of cases [1]. Clinical and histologic features such as mass lesions, high nuclear grade, and the presence of comedonecrosis are associated with higher risk of invasion, but these features have not been shown to reliably predict the presence or absence of an adjacent, unsampled invasive tumor focus [2], [3]. Additional microscopic features and biomarkers have been explored to better predict DCIS behavior. Tumor microenvironment, including the presence of tumor-associated macrophages, may play an important role in the transition from in situ to invasive carcinoma by releasing cytokines, chemokines, and growth factors that contribute to tumor proliferation, progression, and angiogenesis. In particular, type 2, or M2, macrophages have been shown to have protumoral functions in multiple carcinoma types, including breast carcinoma [4]. CD163 is an M2-specific marker that can be used to identify the presence of these particular macrophages in the tumor environment [5]. The presence of CD163-positive cells with DCIS has been shown to be significantly associated with increased risk of progression to invasive carcinoma [6]. The aim of our study was to evaluate the significance of DCIS-associated CD163-positive cells on a breast core biopsy material in predicting adjacent, synchronous invasion on excision.
Section snippets
Materials and methods
After university institutional review board approval, cases of DCIS diagnosed on core biopsy with follow-up excision results were identified by retrospective report search of the electronic pathology database. All cases of low-grade DCIS with subsequent invasion, representing the lowest incidence category in this study, were identified over a 10-year period. Representative matched numbers of cases of low-grade DCIS without invasion as well as intermediate- and high-nuclear-grade DCIS, with and
Results
Fifty-seven total biopsy cases of DCIS were identified to be of low (n = 13), intermediate (n = 21), and high (n = 23) nuclear grade, 27 (47%) of which showed invasion on the subsequent excision specimen. Intratumoral CD163 scores ranged from 0 to 2 (mean, 0.7; Figure B). Stromal CD163 scores ranged from 0 to 3 (mean, 1.3; Figure D). Intratumoral and stromal CD163 levels were not significantly associated with the presence of subsequent invasion when evaluating all combined cases of DCIS
Discussion
With the introduction of routine mammographic screening, the diagnosis of DCIS has increased nearly 5-fold. Current standard of care for DCIS is surgical resection with or without radiation. Because most cases of DCIS are indolent and do not progress to invasive carcinoma [8], surgical management has been questioned recently and less aggressive management options are being pursued. Clinical trials exploring the role of active surveillance of women diagnosed as having DCIS on screening
Conclusions
Although the presence of CD163-positive macrophages has previously been shown to portend increased risk of subsequent DCIS recurrence with invasion, we did not find the presence of such inflammatory cells at the time of diagnostic core biopsy to be predictive of the presence of a concurrent, unsampled invasive tumor. This marker does not therefore seem to be a helpful addition to risk stratification when selecting those patients who may forgo surgical excision.
References (22)
- et al.
Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy
Eur J Cancer
(2006) - et al.
The LORIS trial: addressing overtreatment of ductal carcinoma in situ
Clin Oncol (R Coll Radiol)
(2015) - et al.
Predictors of invasive disease in breast cancer when core biopsy demonstrates DCIS only
J Surg Oncol
(2006) - et al.
Do LORIS trial eligibility criteria identify a ductal carcinoma in situ patient population at low risk of upgrade to invasive carcinoma?
Ann Surg Oncol
(2016) - et al.
Feasibility of the less is more approach in treating low-risk ductal carcinoma in situ diagnosed on core needle biopsy: ten-year review of ductal carcinoma in situ upgraded to invasion at surgery
Arch Pathol Lab Med
(2018) - et al.
Effect of macrophages on breast cancer cell proliferation, and on expression of hormone receptors, uPAR and HER-2
Int J Oncol
(2017) - et al.
Metabolic and immune features of high risk DCIS
Mod Pathol
(2017) - et al.
Diagnostic agreement in the evaluation of image-guided breast core needle biopsies: results from a randomized clinical trial
Am J Surg Pathol
(2004) - et al.
NIH state-of-the-science conference statement: diagnosis and management of ductal carcinoma in situ (DCIS)
NIH Consens State Sci Statements
(2009) - et al.
Surgery versus monitoring and endocrine therapy for low-risk DCIS: the COMET trial
Bull Am Coll Surg
(2017)
Ductal carcinoma in situ of the breast: a systematic review of incidence, treatment, and outcomes
J Natl Cancer Inst
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Disclosures: The authors declare no conflict of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sections