Browsing by Subject "ductal carcinoma in situ"

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    Ductal carcinoma in situ of breast: update 2019
    (Elsevier, 2019-08-28) Badve, Sunil S.; Gökmen-Polar, Yesim; Pathology and Laboratory Medicine, School of Medicine
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    Invasion in breast lesions: the role of the epithelial-stroma barrier
    (Wiley, 2018) Rakha, Emad A.; Miligy, Islam; Gorringe, Kylie L.; Toss, Michael S.; Green, Andrew R.; Fox, Stephen B.; Schmitt, Fernando C.; Tan, Puay-Hoon; Tse, Gary M.; Badve, Sunil; Decker, Thomas; Vincent-Salomon, Anne; Dabbs, David J.; Foschini, Maria P.; Moreno, Filipa; Wentao, Yang; Geyer, Felipe C.; Reis-Filho, Jorge S.; Pinder, Sarah E.; Lakhani, Sunil R.; Ellis, Ian O.; Pathology and Laboratory Medicine, School of Medicine
    Despite the significant biological, behavioural and management differences between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast, they share many morphological and molecular similarities. Differentiation of these two different lesions in breast pathological diagnosis is typically based on the presence of an intact barrier between the malignant epithelial cells and stroma, namely the myoepithelial cell (MEC) layer and surrounding basement membrane (BM). Despite being robust diagnostic criteria, the identification of MECs and BM to differentiate in situ from invasive carcinoma is not always straightforward. The MEC layer around DCIS may be interrupted and/or show an altered immunoprofile. MECs may be absent in some benign locally infiltrative lesions such as microglandular adenosis and infiltrating epitheliosis, and occasionally in non-infiltrative conditions such as apocrine lesions, and in these contexts this does not denote malignancy or invasive disease with metastatic potential. MECs may be also absent around some malignant lesions such as some forms of papillary carcinoma yet these behave in an indolent fashion akin to some DCIS. In Paget's disease, malignant mammary epithelial cells extend anteriorly from the ducts to infiltrate the epidermis of the nipple but do not typically infiltrate through the BM into the dermis. Conversely, BM-like material can be seen around invasive carcinoma cells and around metastatic tumour cell deposits. Here, we review the role of MECs and BM in breast pathology and highlight potential clinical implications. We advise caution in interpretation of MEC features in breast pathology and mindfulness of the substantive evidence base in the literature associated with behaviour and clinical outcome of lesions classified as benign on conventional morphological examination before changing classification to an invasive lesion on the sole basis of MEC characteristics.
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    Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts
    (Elsevier, 2022-12-12) Strand, Siri H.; Rivero-Gutiérrez, Belén; Houlahan, Kathleen E.; Seoane, Jose A.; King, Lorraine M.; Risom, Tyler; Simpson, Lunden A.; Vennam, Sujay; Khan, Aziz; Cisneros, Luis; Hardman, Timothy; Harmon, Bryan; Couch, Fergus; Gallagher, Kristalyn; Kilgore, Mark; Wei, Shi; DeMichele, Angela; King, Tari; McAuliffe, Priscilla F.; Nangia, Julie; Lee, Joanna; Tseng, Jennifer; Storniolo, Anna Maria; Thompson, Alastair M.; Gupta, Gaorav P.; Burns, Robyn; Veis, Deborah J.; DeSchryver, Katherine; Zhu, Chunfang; Matusiak, Magdalena; Wang, Jason; Zhu, Shirley X.; Tappenden, Jen; Ding, Daisy Yi; Zhang, Dadong; Luo, Jingqin; Jiang, Shu; Varma, Sushama; Anderson, Lauren; Straub, Cody; Srivastava, Sucheta; Curtis, Christina; Tibshirani , Rob; Angelo, Robert Michael; Hall , Allison; Owzar , Kouros; Polyak , Kornelia; Maley, Carlo; Marks, Jeffrey R.; Colditz, Graham A.; Hwang, E. Shelley; West , Robert B.; Medicine, School of Medicine
    Ductal carcinoma in situ (DCIS) is the most common precursor of invasive breast cancer (IBC), with variable propensity for progression. We perform multiscale, integrated molecular profiling of DCIS with clinical outcomes by analyzing 774 DCIS samples from 542 patients with 7.3 years median follow-up from the Translational Breast Cancer Research Consortium 038 study and the Resource of Archival Breast Tissue cohorts. We identify 812 genes associated with ipsilateral recurrence within 5 years from treatment and develop a classifier that predicts DCIS or IBC recurrence in both cohorts. Pathways associated with recurrence include proliferation, immune response, and metabolism. Distinct stromal expression patterns and immune cell compositions are identified. Our multiscale approach employed in situ methods to generate a spatially resolved atlas of breast precancers, where complementary modalities can be directly compared and correlated with conventional pathology findings, disease states, and clinical outcome.
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    Refined estimates of local recurrence risks by DCIS score adjusting for clinicopathological features: a combined analysis of ECOG-ACRIN E5194 and Ontario DCIS cohort studies
    (Springer, 2018-06) Rakovitch, E.; Gray, R.; Baehner, F. L.; Sutradhar, R.; Crager, M.; Gu, S.; Nofech‑Mozes, S.; Badve, Sunil S.; Hanna, W.; Hughes, L. L.; Wood, W. C.; Davidson, N. E.; Paszat, L.; Shak, S.; Sparano, J. A.; Solin, L. J.; Pathology and Laboratory Medicine, School of Medicine
    Purpose Better tools are needed to estimate local recurrence (LR) risk after breast-conserving surgery (BCS) for DCIS. The DCIS score (DS) was validated as a predictor of LR in E5194 and Ontario DCIS cohort (ODC) after BCS. We combined data from E5194 and ODC adjusting for clinicopathological factors to provide refined estimates of the 10-year risk of LR after treatment by BCS alone. Methods Data from E5194 and ODC were combined. Patients with positive margins or multifocality were excluded. Identical Cox regression models were fit for each study. Patient-specific meta-analysis was used to calculate precision-weighted estimates of 10-year LR risk by DS, age, tumor size and year of diagnosis. Results The combined cohort includes 773 patients. The DS and age at diagnosis, tumor size and year of diagnosis provided independent prognostic information on the 10-year LR risk (p ≤ 0.009). Hazard ratios from E5194 and ODC cohorts were similar for the DS (2.48, 1.95 per 50 units), tumor size ≤ 1 versus > 1–2.5 cm (1.45, 1.47), age ≥ 50 versus < 50 year (0.61, 0.84) and year ≥ 2000 (0.67, 0.49). Utilization of DS combined with tumor size and age at diagnosis predicted more women with very low (≤ 8%) or higher (> 15%) 10-year LR risk after BCS alone compared to utilization of DS alone or clinicopathological factors alone. Conclusions The combined analysis provides refined estimates of 10-year LR risk after BCS for DCIS. Adding information on tumor size and age at diagnosis to the DS adjusting for year of diagnosis provides improved LR risk estimates to guide treatment decision making.
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    Single-cell heterogeneity in ductal carcinoma in situ of breast
    (Nature, 2018-03) Gerdes, Michael J.; Gökmen-Polar, Yesim; Sui, Yunxia; Pang, Alberto Santamaria; LaPlante, Nicole; Harris, Adrian L.; Tan, Puay-Hoon; Ginty, Fiona; Badve, Sunil S.; Pathology and Laboratory Medicine, School of Medicine
    Heterogeneous patterns of mutations and RNA expression have been well documented in invasive cancers. However, technological challenges have limited the ability to study heterogeneity of protein expression. This is particularly true for pre-invasive lesions such as ductal carcinoma in situ of the breast. Cell-level heterogeneity in ductal carcinoma in situ was analyzed in a single 5 μm tissue section using a multiplexed immunofluorescence analysis of 11 disease-related markers (EGFR, HER2, HER4, S6, pmTOR, CD44v6, SLC7A5 and CD10, CD4, CD8 and CD20, plus pan-cytokeratin, pan-cadherin, DAPI, and Na+K+ATPase for cell segmentation). Expression was quantified at cell level using a single-cell segmentation algorithm. K-means clustering was used to determine co-expression patterns of epithelial cell markers and immune markers. We document for the first time the presence of epithelial cell heterogeneity within ducts, between ducts and between patients with ductal carcinoma in situ. There was moderate heterogeneity in a distribution of eight clusters within each duct (average Shannon index 0.76; range 0–1.61). Furthermore, within each patient, the average Shannon index across all ducts ranged from 0.33 to 1.02 (s.d. 0.09–0.38). As the distribution of clusters within ducts was uneven, the analysis of eight ducts might be sufficient to represent all the clusters ie within- and between-duct heterogeneity. The pattern of epithelial cell clustering was associated with the presence and type of immune infiltrates, indicating a complex interaction between the epithelial tumor and immune system for each patient. This analysis also provides the first evidence that simultaneous analysis of both the epithelial and immune/stromal components might be necessary to understand the complex milieu in ductal carcinoma in situ lesions.
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    Surgical Excision Without Radiation for Ductal Carcinoma in Situ of the Breast: 12-Year Results From the ECOG-ACRIN E5194 Study
    (American Society of Clinical Oncology, 2015) Solin, Lawrence J.; Gray, Robert; Hughes, Lorie L.; Wood, William C.; Lowen, Mary Ann; Badve, Sunil S.; Baehner, Frederick L.; Ingle, James N.; Perez, Edith A.; Recht, Abram; Sparano, Joseph A.; Davidson, Nancy E.; Pathology and Laboratory Medicine, School of Medicine
    Purpose To determine the 12-year risk of developing an ipsilateral breast event (IBE) for women with ductal carcinoma in situ (DCIS) of the breast treated with surgical excision (lumpectomy) without radiation. Patients and Methods A prospective clinical trial was performed for women with DCIS who were selected for low-risk clinical and pathologic characteristics. Patients were enrolled onto one of two study cohorts (not randomly assigned): cohort 1: low- or intermediate-grade DCIS, tumor size 2.5 cm or smaller (n = 561); or cohort 2: high-grade DCIS, tumor size 1 cm or smaller (n = 104). Protocol specifications included excision of the DCIS tumor with a minimum negative margin width of at least 3 mm. Tamoxifen (not randomly assigned) was given to 30% of the patients. An IBE was defined as local recurrence of DCIS or invasive carcinoma in the treated breast. Median follow-up time was 12.3 years. Results There were 99 IBEs, of which 51 (52%) were invasive. The IBE and invasive IBE rates increased over time in both cohorts. The 12-year rates of developing an IBE were 14.4% for cohort 1 and 24.6% for cohort 2 (P = .003). The 12-year rates of developing an invasive IBE were 7.5% and 13.4%, respectively (P = .08). On multivariable analysis, study cohort and tumor size were both significantly associated with developing an IBE (P = .009 and P = .03, respectively). Conclusion For patients with DCIS selected for favorable clinical and pathologic characteristics and treated with excision without radiation, the risks of developing an IBE and an invasive IBE increased through 12 years of follow-up, without plateau. These data help inform the treatment decision-making process for patients and their physicians.