scholarly journals Genomic profiling reveals heterogeneous populations of ductal carcinoma in situ of the breast

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Satoi Nagasawa ◽  
Yuta Kuze ◽  
Ichiro Maeda ◽  
Yasuyuki Kojima ◽  
Ai Motoyoshi ◽  
...  

AbstractIn a substantial number of patients, ductal carcinoma in situ (DCIS) of the breast will never progress to invasive ductal carcinoma, and these patients are often overtreated under the current clinical criteria. Although various candidate markers are available, relevant markers for delineating risk categories have not yet been established. In this study, we analyzed the clinical characteristics of 431 patients with DCIS and performed whole-exome sequencing analysis in a 21-patient discovery cohort and targeted deep sequencing analysis in a 72-patient validation cohort. We determined that age <45 years, HER2 amplification, and GATA3 mutation are possible indicators of relapse. PIK3CA mutation negativity and PgR negativity were also suggested to be risk factors. Spatial transcriptome analysis further revealed that GATA3 dysfunction upregulates epithelial-to-mesenchymal transition and angiogenesis, followed by PgR downregulation. These results reveal the existence of heterogeneous cell populations in DCIS and provide predictive markers for classifying DCIS and optimizing treatment.

Mastology ◽  
2020 ◽  
Vol 30 (Suppl 1) ◽  
Author(s):  
Rebeca Neves Heinzen ◽  
Alfredo Carlos Simões Dornellas de Barros ◽  
Filomena Marino Carvalho ◽  
Cristiane da Costa Brandeia Abrahao Nimir ◽  
Alfredo Luiz Jacomo

Introduction: The nipple-areola complex (NAC) has glandular tissue in intrapapillary ducts (IPDs). When the NAC is preserved during mammary adenectomies (MA) for the treatment of breast cancer (BC), this glandular tissue, which is a potential focus of tumor residues, remains. Objective: To estimate the frequency of neoplastic development in IPDs among BC patients treated with MA. Method: After the MA and with evidence of free retroareolar margin through intraoperative examination, the nipple was inverted, and its central portion, where mammary ducts are located, removed. A pointed-tip scalpel was used, preserving a tissue rim of 1.0 to 2.0 mm. The analysis involved 219 cases submitted to this type of surgery in the Clínica Professor Alfredo Barros. In all patients, the distance tumor-NAC was ≥2.0 cm, according to magnetic resonance imaging (MRI). The intrapapillary tissue removed was sent for microscopic examination of sections embedded in paraffin. Results: We found 4 cases of ductal carcinoma in situ (none infiltrating) in IPDs (1.19%). Considering only the 217 cases with free retroareolar margin in the definitive examination, the number of patients with ductal carcinoma in situ in IPDs decreased to 2 (0.9%). Conclusion: IPDs are rarely involved in selected cases of MA (distance tumor-NAC≥2.0 cm on MRI and free retroareolar margin). Ideally, they should be removed, especially when the intent is avoiding radiotherapy.


2020 ◽  
Vol 27 (1) ◽  
pp. E202017
Author(s):  
Ankit Prabhakar ◽  
Dawood Iqbal Wani ◽  
Shivani Sharma ◽  
Sajjad Ahmad Dar ◽  
Shaafiya Ashraf

Breast carcinoma is a heterogeneous group of tumors with a wide spectrum of clinical presentations, lesion characterization and diagnostic evaluation. Ductal carcinoma in situ accounts for 15%-20% of breast carcinomas detected in screened populations. Ductal carcinoma in situ has a variable appearance on mammography. The use of mammography has become as a very helpful tool for the early detection of larger number of patients with ductal carcinoma in situ and, thus, offering timely surgery and the need for the appropriate radiation treatment to patients. This study was undertaken as a hospital-based retrospective study to evaluate the varied spectrum of mammographic findings in 57 women with histopathological diagnosis of ductal carcinoma in situ. The spectrum of mammographic findings of ductal carcinoma in situ was found to vary widely. A thorough and vigilant inspection of a mammogram is necessary for all the patients to avoid the possibility of missing early diagnosis of this entity, since the findings are very subtle. Most cases show microcalcifications on mammograms and their early detection can help in early diagnosis, thereby offering conservative surgical approach to a patient. Microcalcifications can be present isolated or in association with a mass. These are mostly clustered in distribution followed by regional, segmental and ductal pattern of distribution. The morphology of microcalcifications is mostly amorphous, followed by pleiomorphic and fine heterogenous types. Hence, the mammogram must be interpreted with strict vigilance and proper attention to all aspects for early and correct diagnosis of ductal carcinoma in situ to help in proper guidance of its treatment.


Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 431
Author(s):  
Corrado Chiappa ◽  
Alice Bonetti ◽  
Giulio Jad Jaber ◽  
Valentina De Berardinis ◽  
Veronica Bianchi ◽  
...  

Introduction: Ductal carcinoma in situ (DCIS) is an intraductal neoplastic proliferation of epithelial cells that are confined within the basement membrane of the breast ductal system. This retrospective observational analysis aims at reviewing the issues of this histological type of cancer. Materials and methods: Patients treated for DCIS between 1 January 2009 and 31 December 2018 were identified from a retrospective database. The patients were divided into two groups of 5 years each, the first group including patients treated from 2009 to 2013, and the second group including patients treated from 2014 to 2018. Once the database was completed, we performed a statistical analysis to see if there were significant differences among the 2 periods. Statistical analyses were performed using GraphPad Prism software for Windows, and the level of significance was set at p < 0.05. Results: 3586 female patients were treated for breast cancer over the 9-year study period (1469 patients from 2009 to 2013 and 2117 from 2014 to 2018), of which 270 (7.53%) had pure DCIS in the final pathology. The median age of diagnosis was 59-year-old (range 36–86). In the first period, 81 (5.5%) women out of 1469 had DCIS in the final pathology, in the second, 189 (8.9%) out of 2117 had DCIS in the final pathology with a statistically significant increase (p = 0.0001). From 2009 to 2013, only 38 (46.9%) were in stage 0 (correct DCIS diagnosis) while in the second period, 125 (66.1%) were included in this stage. The number of patients included in clinical stage 0 increased significantly (p = 0.004). In the first period, 48 (59.3%) specimen margins were at a greater or equal distance than 2 mm (negative margins), between 2014 and 2018; 137 (72.5%) had negative margins. Between 2014 and 2018 the number of DCIS patients with positive margins decreased significantly (p = 0.02) compared to the first period examined. The mastectomies number increased significantly (p = 0.008) between the 2 periods, while the sentinel lymph node biopsy (SLNB) numbers had no differences (p = 0.29). For both periods analysed all the 253 patients who underwent the follow up are currently living and free of disease. We have conventionally excluded the 17 patients whose data were lost. Conclusion: The choice of the newest imaging techniques and the most suitable biopsy method allows a better pre-operative diagnosis of the DCIS. Surgical treatment must be targeted to the patient and a multidisciplinary approach discussed in the Breast Unit centres.


2021 ◽  
Vol 6 (6) ◽  

Although some find it controversial, it is possible to differentiate breast ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) using cytology only, with certain limitations. Invasiveness is the consequence of specific biological, i.e. aggressiveness potential of malignant cells, which is different with respect to the pre-existent DCIS, consequentially with different morphology. During the invasion, malignant cells go through multiple morphological changes, losing their epithelial and acquiring mesenchymal features in the fantastic process of epithelial-mesenchymal transition, which explains their morphology in cohabitation with the environment, includes the disruption of intercellular junctions, the increase of mobility and the release of the original epithelium. This mesenchymal-like phenotype supports the migration and invasion of cells, i.e. thus epithelial-mesenchymal transition ensures the tumor dissemination and metastasizing. Therefore, invasiveness can cytologically be “measured” by detecting morphological signs of increase of biological aggressiveness of malignant cells – through the change of their appearance (cytoplasm elongation in malignant squamous cells, i.e. in adenocarcinoma intracytoplasmic lumina, atypical nucleoli, coarsely clumped chromatin, eu-/parachromatin), but also with stromal parameters (disruption of the intercellular matrix, elastin fragments, capillaries endothelium) presented by tumour diathesis, fibroblast proliferation, fragments of elastoid stroma, invasion of connective and/or adipose tissue by groups and individual malignant cells. For the invasion are also very predictive tubular malignant structures, irregular angulated clusters of reduced cohesiveness, absence of benign naked nuclei, polymorph single tumour cells, less myoepithelial cells on tumour groups, fewer microcalcifications and foamy macrophages. Opposite morphological findings suggest DCIS. Even though cytologically we do not see and cannot see the basement membrane, highly likely we can predict the invasion – necessarily and always with the triple-diagnostic approach or clinical-radiological-morphological correlation to every breast lesion, in the representative well cellular sample and with good knowledge of patohistology and cytology


2018 ◽  
Vol 19 (12) ◽  
pp. 3941 ◽  
Author(s):  
Bartlomiej Szynglarewicz ◽  
Piotr Kasprzak ◽  
Piotr Donizy ◽  
Przemyslaw Biecek ◽  
Agnieszka Halon ◽  
...  

Epithelial-mesenchymal transitions (EMTs) have been recently implicated in the process of cancer progression. The aim of this study was to assess how the preoperative expression patterns of EMT biomarkers correlate with the risk of postoperative invasion in ductal carcinoma in situ (DCIS) found on stereotactic breast biopsies. N-cadherin, Snail1, and secreted protein acidic and rich in cysteine (SPARC) immunoreactivity was observed in 8%, 62%, and 38% of tumors, respectively. Snail1 and SPARC expressions were significantly related to N-cadherin expression and to each other. The postoperative upgrading rate was associated with a positive preoperative expression of all biomarkers. Significance of Snail1 and SPARC persisted in multivariate analysis, but the impact of SPARC on invasion was more significant. When these two EMT triggers were considered together, the risk of invasion did not significantly differ between the subtypes of DCIS with single positive expression (SPARC−/Snail1+ vs. SPARC+/Snail1−). However, it was significantly lower in single-positive DCIS when compared to lesions of a double-positive profile (SPARC+/Snail1+). Moreover, there were no cases in the double-negative DCIS (SPARC−/Snail1−), with foci of infiltrating cancer found postoperatively in residual postbiopsy lesions. In contrast, DCIS with a combined high SPARC and Snail1 expression (intermediate or strong) had an invasive component in 66–100% of tumors.


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