Abstract 5308: Tissue-based heterogeneity in lobular carcinoma in situ
Authors: Nyante Sarah J. , Ozdowski Emily , Tan Xianming , Lawton Thomas J. 
Published: July 2017

Abstract
Lobular carcinoma in situ (LCIS) is a preinvasive breast lesion associated with a 6 to 11-fold increased risk of invasive breast cancer. Despite this increased risk, little is known regarding what qualities of LCIS predispose individual patients to invasive cancer. Given recent advances in understanding of the importance of etiologic heterogeneity within breast cancer, we sought to characterize morphologic markers of heterogeneity in LCIS and surrounding tissue, with the hypothesis that features with lesional variation may be important candidate predictors of breast cancer risk. We identified 64 patients aged ≥ 18 years who were diagnosed with LCIS at a single institution from 2004-2014. Patients with concurrent invasive breast cancer in the same breast were excluded. Archival slides of each case were reviewed by an experienced breast pathologist to confirm the presence of LCIS and characterize the LCIS type (classic, florid, or pleomorphic). The number of lobules involved with LCIS, presence of calcifications or necrosis associated with LCIS, and presence of other benign lesions [atypical lobular hyperplasia (ALH), atypical ductal hyperplasia (ADH), flat epithelial atypia, fibroadenoma, intraductal papilloma] were recorded. Age at surgery and surgery type were abstracted from medical records. The two-sided Fisher’s exact test was used to examine differences in proportions. The mean age of the cases was 53 years, and the most common surgery type was excisional/incisional biopsy or lumpectomy (55%), followed by core biopsy (25%) and mastectomy (20%). Calcifications were associated with LCIS in 41% of cases. Women were more likely to have florid LCIS when calcifications were present compared to when calcifications were absent (P&lt;0.01). Additionally, cases with calcifications were more likely to have more than 10 lobules affected by LCIS (P&lt;0.01). Associations between calcifications and extent of LCIS persisted when the sample was restricted to cases where classic LCIS was the primary type. Moreover, the presence of calcifications was not associated with surgery type (P=0.36), suggesting that the results were not due to sampling bias. Other benign lesions were present in the majority of cases, but were not associated with LCIS characteristics (all P&gt;0.05). ALH was the most common other lesion, present in 70% of samples.. Our results demonstrate that LCIS-associated calcifications are common and are associated with more extensive disease, even among LCIS characterized as ‘classic’. In invasive breast cancer, the presence of certain types of calcifications has been associated with poor prognosis. A next step in this research is to understand whether the heterogeneity we observed in LCIS can be ascribed to a specific calcification morphology and/or distribution. Understanding this will help us elucidate the potential biological mechanism and determine whether LCIS calcifications are a viable marker for the prediction of breast cancer risk.
Citation Format: Sarah J. Nyante, Emily Ozdowski, Xianming Tan, Thomas J. Lawton. Tissue-based heterogeneity in lobular carcinoma in situ [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5308. doi:10.1158/1538-7445.AM2017-5308