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Review
. 2022 Apr 1;163(4):bqac027.
doi: 10.1210/endocr/bqac027.

Ductal Carcinoma In Situ of Breast: From Molecular Etiology to Therapeutic Management

Shelby Lynn Hophan  1 , Olena Odnokoz  2 , Huiping Liu  3 , Yuan Luo  4 , Seema Khan  5 , William Gradishar  6 , Zhuan Zhou  7 , Sunil Badve  8 , Mylin A Torres  9 , Yong Wan  2   9
Affiliations
Review

Ductal Carcinoma In Situ of Breast: From Molecular Etiology to Therapeutic Management

Shelby Lynn Hophan et al. Endocrinology. .

Abstract

Ductal carcinoma in situ (DCIS) makes up a majority of noninvasive breast cancer cases. DCIS is a neoplastic proliferation of epithelial cells within the ductal structure of the breast. Currently, there is little known about the progression of DCIS to invasive ductal carcinoma (IDC), or the molecular etiology behind each DCIS lesion or grade. The DCIS lesions can be heterogeneous in morphology, genetics, cellular biology, and clinical behavior, posing challenges to our understanding of the molecular mechanisms by which approximately half of all DCIS lesions progress to an invasive status. New strategies that pinpoint molecular mechanisms are necessary to overcome this gap in understanding, which is a barrier to more targeted therapy. In this review, we will discuss the etiological factors associated with DCIS, as well as the complexity of each nuclear grade lesion. Moreover, we will discuss the possible molecular features that lead to progression of DCIS to IDC. We will highlight current therapeutic management and areas for improvement.

Keywords: breast cancer; ductal carcinoma in situ; invasive breast cancer; invasive ductal carcinoma.

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Figures

Figure 1.
Figure 1.
Stages of breast cancer progression.
Figure 2.
Figure 2.
Grading and characteristics of DCIS. Ductal carcinoma in situ (DCIS) lesions are classified based on their hormone receptor status, morphology, and comedo status. The DCIS grades are Grade I (low grade), Grade II (intermediate grade), and Grade III (high grade). Grade I and II lesions are less likely to develop into invasive ductal carcinoma (IDC); however, Grade III lesions are at higher risk of breaking through the basement membrane into surrounding breast tissue. Comedonecrosis, or buildup of dead cells inside the tumor, is often present in Grade III DCIS lesions. The microenvironment surrounding the DCIS cells, including myoepithelial cells, fibroblasts, and lymphocytes, contributes to progression of the lesions.
Figure 3.
Figure 3.
Evolutionary models of DCIS progression. Independent evolution method allows the theory that DCIS (in situ) and invasion cells evolve independently of each other. These cells originate from 2 different normal cells within the breast environment. Evolutionary Bottleneck proposes that evolution of 3 subpopulations have a single clonal ancestral cell, from which a single cell is selected to become invasive. Multiclonal Invasion is similar to Evolutionary Bottleneck; however, all 3 clonal cells escape in situ and migrate into adjacent tissues to become invasive.
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References

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