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Item Ductal carcinoma in situ of breast: update 2019(Elsevier, 2019-08-28) Badve, Sunil S.; Gökmen-Polar, Yesim; Pathology and Laboratory Medicine, School of MedicineItem 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 MedicineDespite 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.Item 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 MedicinePurpose 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.